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FDA Seeks $7.2 Billion to Protect and Advance Public Health

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FDA Seeks $7.2 Billion to Protect and Advance Public Health

March 09, 2023: “The U.S. Food and Drug Administration announced it is requesting $7.2 billion as part of the president’s fiscal year (FY) 2024 budget.

This funding will allow the agency to continue to leverage new and emerging technologies, recruit and support a highly skilled workforce and adapt oversight to new production and business models.

This is work that will have an immediate impact on food, tobacco and medical product safety in this country while also preparing the agency to address rapid innovation across the food and medical products fields.

The request includes an increase of $372 million in budget authority — or 10% above the FY 2023 Enacted Level — and a $150 million increase in user fees. 

“This year’s funding request builds on our accomplishments and lessons learned over the past year and adds new funding to continue modernizing the FDA and its capabilities for the future.

We continue to deliver on a wide range of priorities and have strategically focused our request to ensure our program areas have the funding they need to operate with the highest success for the good of public health,” said FDA Commissioner Robert M. Califf, M.D.

“Our investments to strengthen medical product safety and availability, along with funding for vital oversight of tobacco products continue to be a central focus.

The budget also provides a historic investment to strengthen the FDA’s food safety and nutrition capacity—especially for infants and young children, demonstrating the Administration’s ongoing commitment to these responsibilities.

As always, our foremost focus is on the well-being of patients and consumers, and we look forward to continuing our work with Congress to help meet the critical public health challenges ahead.”

The FY 2024 request, which covers the period from Oct. 1, 2023, through Sept. 30, 2024, includes new efforts for high priority program areas. Highlights of the agency’s request include:

Enhancing Food Safety, Nutrition and Cosmetics

  • $128.2 million in investments in food safety and nutrition modernization, including food labeling and animal food safety oversight. 
    While the agency is in the process of defining its future vision for the Human Foods Program, there is significant need for additional resources to strengthen its foundational food safety and nutrition capacity.
    The budget seeks to strengthen consumer protection and implement lasting solutions for more efficient operations through continued investments in the New Era of Smarter Food Safety.
    Building on lessons learned from the infant formula supply chain response, the budget includes funding to modernize infant formula oversight and strengthen efforts to respond to shortages of critical foods, empower consumers to make healthier food choices and reduce exposure to toxic chemicals in the food supply.
    The budget will also help position the FDA to keep pace with innovative and novel technologies being used to develop animal food ingredients while addressing foundational gaps in the oversight of the animal food industry as these ingredients are combined, packaged, and sold as animal food. 
  • $5 million toward modernizing oversight of cosmetics. The budget includes new funding for the development of regulations, compliance policies, product registration and listing platforms, adverse event reporting and other activities to start to implement new authorities recently signed into law related to the safety and proper labeling of cosmetic products. 

Advancing Access to Safe and Effective Medical Products

  • $23 million in additional funds to advance the goal of ending the opioid crisis. Funding will support broader development of opioid overdose reversal treatments and treatments for substance use disorders and enhance regulatory oversight, expand compliance, enforcement and laboratory support.
    Additionally, the budget request assists in advancing the development, evaluation and market authorizations of related digital health medical devices. 
  • $11.6 million increase toward improving the medical device supply chain and shortage programs. The agency will continue to build its capabilities to ensure patients have access to medical devices at all times.
    The budget will allow the FDA to expand efforts to work proactively with medical device companies, health care providers, device distributors, and patients to enhance resiliency in the supply chain of critical medical devices and prevent shortages of critical devices that most often impact vulnerable populations. 
  • $2.5 million to implement ACT for ALS to foster development of treatments for ALS and other rare neurodegenerative diseases. 
    To help the FDA implement the ACT for ALS Act, additional funding will strengthen the FDA’s ability to issue new grants and contracts, hire dedicated expert staff and allow the FDA to facilitate access to investigational therapies and medical devices for neurodegenerative diseases such as amyotrophic lateral sclerosis (i.e., ALS, also known as Lou Gehrig’s disease, a progressive and fatal disease).

Reigniting Cancer Moonshot

  • $50 million to advance the president’s Cancer Moonshot goals. This funding will advance the President’s Cancer Moonshot, including by expanding resources and collaborations for innovative and new diagnostic and therapeutic products to treat rare cancers, and other efforts to address cancer morbidity and mortality.
    This budget will enhance efforts to improve evidence generation for underrepresented subgroups in oncology clinical trials, and to support pragmatic and decentralized trials and our sources of evidence through patient-generated data, learnings, and real-world evidence.
    Additionally, these resources will also assist the FDA’s expansion of its efforts to facilitate the approvals of innovative and new cancer treatments by international regulatory authorities at the time of the FDA’s approval and will foster collaboration of cancer treatments in other countries with standards comparable to the U.S. standard of care.  

    Strengthening Public Health and Mission Support Capacity
  • $10 million in further investments in enterprise data and IT modernization. The budget will expand data exchange capabilities and underlying technology platforms to better meet the challenges of the FDA’s programs and mission-critical responsibilities.

    Specific focuses include emerging threats, supporting needs for real-time evaluation, and more continuously accessing, analyzing and aggregating multiple sources of information, such as for recalls, adverse events, outbreaks and pandemics.  
  • $16 million for regulatory and mission support functions within the Office of the Commissioner. These resources will enable the FDA to provide the appropriate crosscutting strategic direction, policy coordination, and business services to ensure that the FDA’s programs operate effectively, efficiently, and are well coordinated.

    The budget includes funding for the new enterprise transformation effort to improve business process, data and technology management that will allow us to work more efficiently and optimize the use of the vast amount of data that is the foundation of our work. 
  • $9.4 million for FDA buildings, facilities and infrastructure improvements. The budget includes additional funding to help ensure that the FDA’s offices and laboratories across the country are secure, modern, reliable and cost-effective spaces that empowers the FDA’s workforce to protect and promote the safety and health of American families.

To complement the funding requests, the agency’s budget proposal also includes a package of legislative proposals designed to bolster the FDA’s authorities to further its mission to protect and promote public health. Notable proposals include efforts to: 

  • Require animal drug sponsors to make post-approval safety-related labeling changes based on new data; develop programs for safe use of certain products; and require post-approval studies based on new safety information that becomes available after approval.  
  • Provide the FDA the ability to exclude certain products or classes of products that the FDA and the Environmental Protection Agency (EPA) agree are more appropriately regulated by the EPA as pesticides; and facilitate an orderly transfer of regulatory responsibility from the EPA to the FDA of specified products that are currently registered as pesticides that the two agencies agree are more appropriately regulated by the FDA as animal drugs.

    The proposed changes would remove regulatory uncertainty and provide clarity to sponsors about which agency intends to regulate a given product or type of products. 
  • Expand the drug shortage notification requirements to include situations when a drug manufacturer is unlikely to be able to meet an increased demand. Currently, the FDA generally does not receive notice or adequate information from drug manufacturers regarding increases in demand that would position the agency to assist in preventing or mitigating drug shortages. 

  • Broaden the FDA’s authority to request records or other information in advance of or in lieu of inspections to include all FDA-regulated product areas, explicitly to include food, tobacco products and cosmetic establishments.

    Currently remote regulatory inspections are limited to drug, device and biomedical research, with only drug assessments requiring mandatory participation.

    This proposal will promote regulatory compliance and help facilitate certain oversight activities prior to arriving for or instead of an inspection. 
  • Remove limitations that require manufacturers to notify the FDA about interruptions or discontinuances in the manufacture of certain medical devices only during or in advance of a Public Health Emergency (PHE).
    Medical device shortages occur in many situations that fall outside of or are unrelated to PHEs, including natural or human-made disasters, recalls, geopolitical conflicts, production shutdowns and cybersecurity incidents.
    These events can lead to device shortages that significantly impact patient care and jeopardize healthcare worker safety.
    Therefore, the FDA is seeking the requirement for manufacture notifications at all times, as well as the authority to require and review risk management plans to help ensure that manufacturers are prepared for situations where their ability to manufacture product may be disrupted or may be insufficient to meet demand. 
  • Expand the FDA’s mandatory recall authority to cover all human and animal drugs.
    The agency currently has authority to order the recall of controlled substances, biological products, medical devices, tobacco products, cosmetics and foods.
    The agency lacks mandatory recall authority for other human and animal drugs.  
  • Enhance tools to help reduce exposure to toxic elements in the food supply, including food consumed by infants and young children.
    The FDA is seeking new authority to establish binding contamination limits in food and efficiently update such limits as new scientific information becomes available. 
  • Require industry to test final food products marketed for consumption by infants and children for toxic elements and allow FDA access to those records.
    This new authority would help the FDA better understand levels of toxic elements in these products, allow the FDA to monitor industry progress in reducing levels of these toxic elements over time and identify where the FDA should devote more time and resources. 
  • Assess user fees on and collect fees from manufacturers and importers of all tobacco products.
    The budget also requests an additional $100 million in funding to support regulatory activities including for oversight of e-cigarettes, which currently have high rates of youth use.
    The additional funding will support hiring more staff and help the FDA strengthen its tobacco product work—including application reviews, compliance and enforcement, policy development and research programs.

https://www.fda.gov/news-events/press-announcements/fda-seeks-72-billion-protect-and-advance-public-health-enhancing-food-safety-and-advancing-medical

AstraZeneca launches call for entries to the 2023 global R&D Postdoctoral Challenge

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AstraZeneca launches call for entries to the 2023 global R&D Postdoctoral Challenge

March 10, 2023: “AstraZeneca has announced the launch of the 2023 R&D Postdoctoral Challenge, an initiative designed to accelerate ideas to transform the treatment of some of the world’s most complex diseases.

The R&D Postdoctoral Challenge has been designed to drive R&D productivity, promote diversity of thought and stimulate research opportunities across the globe.

Unlike standard postdoctoral positions, the Challenge encourages applicants from anywhere around the world to devise their own research projects and help advance the next wave of therapeutics for people who need them most.

This follows the success of the inaugural 2022 programme in which six finalists were awarded fully funded research positions within the Company.

Submissions for the 2023 Challenge are open to final-year MD and/or PhD students and postdoctoral researchers until 30 June and successful candidates will compete to be awarded a fully funded postdoctoral research position and join the vibrant scientific community within AstraZeneca.

Working alongside a leading university, researchers will also receive access to in-house expertise, compounds, novel tools and technologies and mentoring support to develop their ideas and innovate.

Prof. Sir Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Our ambition through the R&D Postdoctoral Challenge is to promote a rich tapestry of ideas and create a diverse, global community of researchers with access to AstraZeneca’s cutting-edge facilities and world-leading expertise.

Last year, we were able to support all six of our finalists, and I am looking forward to seeing this year’s entries and helping even more early-career scientists translate their ideas into meaningful benefits for patients.”

Shortlisted applicants will have the chance to pitch their research ideas to a panel consisting of AstraZeneca leaders and external life science leaders in September, with the selection of finalists decided later in the year.

Proposals will be reviewed based on scientific merit, and their potential to create real impact for patients, society and healthcare systems.

Further information on the R&D Postdoctoral Challenge, including entry criteria and details on how to submit innovative research proposals, can be found at:

https://openinnovation.astrazeneca.com/rd-postdoctoral-challenge.html.

The R&D Postdoctoral Challenge forms part of AstraZeneca’s Early Talent programmes, nurturing the science leaders of tomorrow and encouraging diversity of thought within an environment that enables science to thrive. 

AstraZeneca’s global R&D footprint and productivity
In 2022 AstraZeneca invested $9.5 billion in R&D which represents 21% of Total Revenue, in order to continue to discover and develop medicines which transform the lives of patients.

The Company has three world class strategic R&D centres including The Discovery Centre (DISC) in Cambridge in the UK, one in Gaithersburg, Maryland in the greater Washington, D.C. region of the US, and another in Gothenburg in Sweden, as well as further hubs across the world.

It has integrated R&D teams and accelerated decision-making processes, using its unique scientific capabilities, to deliver one of the most productive pipelines in the industry.  

Since 2005, AstraZeneca has achieved an almost six-fold improvement in the proportion of its pipeline molecules that have advanced from preclinical investigation to completion of Phase III clinical trials – from 4% to 23%. This improvement moves AstraZeneca well above the current industry average success rate of 14% in the 2018-2020 timeframe.

Of the Company’s 80,000 employees, more than 13,000 work exclusively in R&D.

In 2021, its scientists published a total of 871 manuscripts, with 196 in high impact peer-review journals (impact factor greater than or equal to 15 according to Reuters five-year rating), compared to one in 2010.”

https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-launches-call-for-entries-to-the-2023-global-rd-postdoctoral-challenge.html

New organ-on-chip pilot seeks to reduce animal testing in consumer health industry

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New organ-on-chip pilot seeks to reduce animal testing in consumer health industry

March 07,2023: “A first-of-its-kind collaboration in the consumer health industry is developing a platform aimed at reducing or replacing animal testing using “organ-on-chip” (OoC) technology and interactive computational software.

The pilot project, supported by esqLABS, Dynamic42, Placenta Lab of Jena University Hospital, and Bayer’s Consumer Health Division aims to generate clinically relevant data, a key step in evaluating new drug candidates in preclinical research.

The one-year pilot will focus on evaluating whether small molecules can cross the blood-placenta-barrier in pregnant women, an understudied population due to challenges in conducting clinical research.

The platform will consist of a microphysiological system (MPS, so called “organ-on-chip”) representing the main human tissues involved in drug disposition (liver, intestine, placenta) as well as a pumping system to circulate cell culture media among the tissues.

The platform will be digitalized to simulate the distribution of compounds and translate the data to human situations.

While animal tests are often required by regulation in the preclinical phase of new drug development, there can be challenges in translating outcomes from animals to humans in some cases.

If successful, the platform could help reduce animal testing while improving development outcomes, reducing costs, and last but not least improving patient safety.

Under the terms of the agreement, the companies will bring together esqLABS’ unique expertise in computational modelling of biomedical systems, Dynamic42’s expertise in in-depth tissue and hardware engineering as well as Bayer’s leading expertise in human pharmacokinetic predictions to create the integrated biological and computational platform.

The Placenta Lab provides unique experience in developing and building a placenta-on-chip, which is the key element in this study. esqLABS will develop the computational software tool, and Dynamic42 will develop a multi-organ-on-chip platform including the placental barrier.

Bayer will provide industry guidance for real-world usage, as well as drug and data sets to help validate the platform’s predictions. Financial details were not disclosed. 

Partner quotes
“At esqLABS, we develop software solutions for translational research in the Life Sciences. Our solutions can be leveraged at critical decision points in pre-clinical drug development and the MPS platform that we are developing as a team is a great example integrating virtual twins with bioengineering.

We are very excited to work with the scientists from Bayer, Dynamic42, and the Placenta Lab through this collaboration,” said Dr. Christian Maass, OoC-Research Lead at esqLABS.

“The consortium shares a common vision and sees an opportunity to design a platform that predicts whether compounds cross the blood-placenta-barrier.

This is an unprecedented endeavour and we are very excited to be part of this journey.”  adds Dr. Stephan Schaller, CEO of esqLABS.

“Dynamic42 has performed many studies for pharmaceutical purposes in recent years, but this is clearly something new and exciting for us.

Challenging the potential of MPS in a multi-organ setting and combining it with in silico predictions is not just a great concept, it perfectly falls in line with new guidelines for pre-clinical drug testing that have been approved recently by the U.S. government in the FDA Modernization Act 2.0.

This specifically allows and encourages the use of smart combinations of new technologies and approaches to minimize or replace animal testing.

This collaboration between esqLABS, the Placenta Lab of Jena University Hospital, Dynamic42 and Bayer has the potential to lead to a transformational change in how we evaluate human pharmacokinetics, without dosing humans,” said Martin Raasch, CEO of Dynamic42.

“The Placenta Lab is active in a broad spectrum of research topics around human reproduction and pregnancy.

Some of our current projects are focused on trophoblast and immunological research, toxicology, and alternatives to animal experiments, since species differences are among the main reasons for the high failure rate of preclinical studies.

This collaboration represents a great milestone for the development of new mechanisms for the study of the placenta barrier and its bi-directional selective transport in humans.

The strengths of esqLABS, Dynamic42 and Bayer, combined with our experience in the field, work synergistically to offer a path from bench to bedside,” said Priv.-Doz. Dr. Diana Morales, Deputy head and scientist group leader of Placenta Lab.

“Bayer collaborates intensively with stakeholders at national and international levels to develop alternative methods in order to achieve a continuous reduction in the number of animal studies.

It has been a major concern of Bayer for years to minimize animal testing according to the 3R principles (Reduce, Refine and Replace).

We are thrilled to collaborate with scientists from esqLABS, Dynamic42, and the Placenta Lab through this joint project to find novel ways to minimize animal testing and at the same time seek to generate more reliable and accurate data for product’s safety and efficacy,” said Assoc. Prof. Ramy Ammar, Emerging Science and Innovation Director for Digestive Health at Bayer’s Consumer Health Division.”

https://www.bayer.com/media/en-us/new-organ-on-chip-pilot-seeks-to-reduce-animal-testing-in-consumer-health-industry/

FDA Proposes New Requirements for Tobacco Product Manufacturing Practices

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FDA Proposes New Requirements for Tobacco Product Manufacturing Practices

March 08, 2023: “The U.S. FDA is proposing new requirements for tobacco product manufacturers regarding the manufacture, design, packing and storage of their products.

These proposed requirements would help protect public health by, among other things, minimizing or preventing contamination and limiting additional risks by ensuring product consistency.

“While no tobacco product is safe, this proposed rule is intended to minimize or prevent additional risks associated with these products,” said Brian King, Ph.D., M.P.H., director of the FDA’s Center for Tobacco Products.

“Once finalized, it would establish requirements for tobacco product manufacturers that will help protect public health.”

These proposed new requirements would help ensure that the public health is protected and products comply with the Federal Food, Drug, and Cosmetic Act.

For example, these requirements would help minimize or prevent the manufacture and distribution of tobacco products contaminated with foreign substances—such as metal, glass, and plastics—which have been found in tobacco products.

The proposed rule would also help address issues related to inconsistencies between e-liquid product labeling and the actual concentrations in e-liquids; such variability can be misleading to consumers, potentially intensifying addiction and exposure to toxins.

The proposed rule would also establish several requirements related to the identification, tracing and corrective actions for tobacco products that don’t meet specifications or are contaminated, including for tobacco products that have already been distributed.

In the event of an issue, these requirements would require manufacturers to take corrective actions, which may include conducting a recall.

These proposed requirements apply to manufacturers of finished and bulk tobacco products.

As laid out in the proposed rule, a finished tobacco product is a tobacco product, including any component or part, sealed in final packaging; for example, a pack of cigarettes or a can of moist snuff.

A bulk tobacco product is a tobacco product that isn’t sealed in final packaging, but is otherwise suitable for consumer use. 

The proposed rule establishes a framework for manufacturers to adhere to, including: 

  • establishing tobacco product design and development controls;
  • ensuring that finished and bulk tobacco products are manufactured according to established specifications; 
  • minimizing the manufacture and distribution of tobacco products that don’t meet specifications;
  • requiring manufacturers to take appropriate measures to prevent contamination of tobacco products; 
  • requiring investigation and identification of products that don’t meet specifications to institute appropriate corrective actions, such as a recall; and
  • establishing the ability to trace all components or parts, ingredients, additives and materials, as well as each batch of finished or bulk tobacco product, to aid in investigations of those that don’t meet specifications. 

The FDA will hold a public oral hearing on April 12 to gather additional comments from stakeholders, including industry, the scientific community, advocacy groups, and the public.

The proposed rule also will be available for public comment for 180 days. The agency will review all comments as part of the rulemaking process for this foundational rule.

“We remain committed to transparency and stakeholder engagement, including providing clarity to industry so that they are equipped to comply with the law,” said Dr. King.

“We encourage all interested individuals and organizations to participate in the rulemaking process. When the public submits a comment based on sound grounds, that can make an important difference in the agency’s decision-making.”    

The FDA will also hold a meeting of the Tobacco Products Scientific Advisory Committee (TPSAC) on May 18 to seek recommendations from the agency’s outside panel of experts on the requirements laid out in the proposed rule.

As part of the TPSAC meeting, the public will have an opportunity to make oral presentations. The FDA intends to make TPSAC meeting materials available on its website no later than 48 hours before the meeting. 

https://www.fda.gov/news-events/press-announcements/fda-proposes-new-requirements-tobacco-product-manufacturing-practices

Imfinzi significantly improved event-free survival in AEGEAN Phase III trial for patients with resectable nSCLC

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Imfinzi significantly improved event-free survival in AEGEAN Phase III trial for patients with resectable nSCLC

March 09, 2023: “Positive high-level results from a planned interim analysis of the AEGEAN Phase III, placebo– controlled trial showed that treatment with AstraZeneca’s Imfinzi (durvalumab) in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery demonstrated a statistically significant and clinically meaningful improvement in event-free survival (EFS) versus neoadjuvant chemotherapy alone followed by surgery for patients with resectable early-stage (IIA-IIIB) non-small cell lung cancer (NSCLC).

Results from the final pathologic complete response (pCR) and major pathologic response (mPR) analyses were consistent with previously announced positive results.

The trial will continue as planned to assess key secondary endpoints including disease-free survival (DFS) and overall survival (OS).

Each year there are an estimated 2.2 million people diagnosed with lung cancer globally with 80-85% of patients diagnosed with NSCLC, the most common form of lung cancer.

Approximately 25-30% of all patients with NSCLC are diagnosed early enough to have surgery with curative intent.

However, only around 56-65% of patients with Stage II disease will survive for five years.

This decreases to 41% for patients with Stage IIIA and 24% for patients with Stage IIIB disease, reflecting a high unmet medical need.

John V. Heymach, MD, PhD. Professor and Chair Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, said: “Treating patients early with durvalumab both before and after surgery delivers a significant and clinically meaningful benefit in resectable non-small cell lung cancer, where new options are urgently needed to offer patients the best chance of long-term survival.

The AEGEAN results provide compelling evidence that this novel durvalumab regimen can drive improved outcomes in this curative-intent setting.”

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Patients with resectable non-small cell lung cancer face unacceptably high rates of recurrence, despite treatment with chemotherapy and surgery.

We have shown that adding Imfinzi both before and after surgery significantly increased the time patients live without recurrence or progression events. We will continue to follow patients for overall survival.”

Imfinzi was well tolerated and no new safety concerns were observed in the neoadjuvant and adjuvant settings.

Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not increase complications or adverse events, or compromise patients’ ability to undergo surgery versus chemotherapy alone.

These data will be presented at a forthcoming medical meeting and shared with global health authorities.

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in development for patients with lung cancer. In addition to these results, the Company is also announcing today that  Tagrisso (osimertinib) met a secondary endpoint of OS in the ADAURA Phase III trial in early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) NSCLC after complete tumour resection with curative intent.

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths. Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC).

The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.

Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.

For patients with resectable tumours, the majority eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.

AEGEAN
AEGEAN is a randomised, double-blind, multi-centre, placebo-controlled global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB (Eighth Edition AJCC Cancer Staging Manual) NSCLC, irrespective of PD-L1 expression.

Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy.

In the trial, 802 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery. 

Patients with known EGFR or ALK genomic tumour aberrations were excluded from the primary efficacy analyses.

In the AEGEAN trial, the primary endpoints were pCR, defined as no viable tumour in the resection specimen (including lymph nodes) following neoadjuvant therapy, and EFS, defined as the time from randomisation to an event like tumour recurrence, progression precluding definitive surgery, or death.

Key secondary endpoints were mPR, defined as residual viable tumour of less than or equal to 10% in the resected primary tumour following neoadjuvant therapy, DFS, OS, safety and quality of life.

The final pathologic response analyses were performed after all patients had the opportunity for surgery and pathology assessment per the trial protocol.

The trial enrolled participants in 264 centres in more than 25 countries including in the US, Canada, Europe, South America and Asia.

Imfinzi
Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

Imfinzi is the only approved immunotherapy and the global standard of care in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after chemoradiation therapy based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial.

In an exploratory analysis in 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.

Additionally, Imfinzi is approved in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC in the US, EU and Japan based on the POSEIDON Phase III trial.

In addition to its indications in lung cancer, Imfinzi is also approved in combination withchemotherapy in locally advanced or metastatic biliary tract cancer in the US, EU, Japan and several other countries; in combination with Imjudo in unresectable hepatocellular carcinoma in the US, EU and Japan; and in previously treated patients with advanced bladder cancer in several countries.

Since the first approval in May 2017, more than 150,000 patients have been treated with Imfinzi.

AstraZeneca has several ongoing registrational trials focused on testing Imfinzi in earlier stages of lung cancer, including in resectable NSCLC (ADJUVANT BR.31) and unresectable NSCLC (PACIFIC-2, 4, 5, 8 and 9), and in limited-stage SCLC (ADRIATIC).

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, several gastrointestinal (GI) cancers, ovarian cancer, endometrial cancer and other solid tumours.”

https://www.astrazeneca.com/media-centre/press-releases/2023/imfinzi-improved-efs-in-resectable-lung-cancer.html

 

Bayer’s Nubeqa™ receives EU approval for additional indication in prostate cancer

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Bayer’s Nubeqa™ receives EU approval for additional indication in prostate cancer

March01,2023: “The European Commission has granted marketing authorization in the European Union for Nubeqa™ (darolutamide), an oral androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) in combination with docetaxel, for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Nubeqa is already approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease.

“Today’s approval of Nubeqa represents a significant milestone in addressing unmet medical needs for people living with metastatic hormone-sensitive prostate cancer in Europe,” said Christine Roth, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit.

“We are committed to improving prostate cancer care across all stages of the disease and recognize that for patients and their families, quality of life is just as critical as prolonging survival and delaying disease progression.

We continue in our mission to redefine what it means to live with prostate cancer.”

The EU approval is based on the positive results from the Phase III ARASENS trial, which demonstrated that darolutamide plus ADT in combination with docetaxel significantly reduced the risk of death by 32.5% compared to ADT with docetaxel, in patients with mHSPC.

Additionally, the darolutamide combination showed consistent benefits across clinically relevant secondary endpoints, with the overall incidence of treatment-emergent adverse events being similar between treatment arms.

“The approval of Nubeqa in mHSPC in Europe is a major step forward for patients and their treating physicians, expanding the treatment options available and our ability to improve clinical outcomes for those living with the disease,” said Prof. Bertrand Tombal, Professor of Urology at the Université catholique de Louvain (UCL), Cliniques universitaires Saint-Luc, Brussels, Belgium.

“This approval is supported by robust data from the ARASENS clinical trial, which demonstrate the benefits of darolutamide plus ADT in combination with docetaxel in extending survival, delaying disease progression and maintaining quality of life for patients with metastatic hormone-sensitive prostate cancer.”

Prostate cancer is the most commonly diagnosed cancer in men in almost all northern and western European countries.

Only 30% of men with mHSPC will survive five years or more after diagnosis.

Most men with mHSPC eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited long-term survival.

Nubeqa is being investigated in a broad development program with an additional three ongoing or planned large clinical studies, to investigate its potential across prostate cancer patients from the early- to the late-stage of this disease.

This includes the ARANOTE Phase III trial evaluating darolutamide and ADT versus ADT alone for mHSPC.

Nubeqa is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

Bayer is responsible for global commercialization, with co-promotion from Bayer and Orion Corporation in certain European markets, e.g. France, Germany, Italy, Spain, the UK, Scandinavia and Finland.

About the ARASENS Trial
The ARASENS trial is the only randomized, Phase III, multi-center, double-blind, trial which was prospectively designed to compare the use of a second-generation oral androgen receptor inhibitor (ARi), darolutamide, plus ADT in combination with docetaxel to ADT plus docetaxel (a guideline recommended standard-of-care) in metastatic hormone-sensitive prostate cancer (mHSPC).

A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, plus ADT in combination with docetaxel.

The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all evaluated at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability.

Results from this trial were published in the New England Journal of Medicine. A plain language summary publication of these data was published in Future Oncology.

The ARASENS trial demonstrated that darolutamide plus ADT in combination with docetaxel significantly reduced the risk of death by 32.5% compared to ADT with docetaxel alone.

Improvements in the secondary endpoints supported the benefit observed in the primary endpoint, overall survival.

About Metastatic Hormone-Sensitive Prostate Cancer
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.

In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy.

Upon relapse, when the disease will metastasize or spread, or if the disease is newly diagnosed, but has already spread, the disease is hormone-sensitive and androgen deprivation therapy (ADT) is the cornerstone of treatment.

Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of ADT and docetaxel.

Despite these treatments, a large proportion of men with mHSPC will eventually experience progression to metastatic castration-resistant prostate cancer (mCRPC), a condition with high morbidity and limited survival.

About Nubeqa™ (darolutamide)
Nubeqa™ (darolutamide) is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells.

The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans.

This is supported by the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial and the improved verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.

The product is approved in more than 80 countries around the world, including the U.S., EU, Japan and China, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease.

It is also approved for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a number of markets including the U.S and Japan. Filings in other regions are underway or planned. Bayer expects the peak sales potential for Nubeqa to exceed €3 billion.

The compound is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for mHSPC, as well as the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence.

Information about these trials can be found at www.clinicaltrials.gov.

In addition, a study to explore the potential of darolutamide in the early setting for patients who have experienced a rise in their prostate specific antigen (PSA) levels following surgery or radiation, is also planned.

About Prostate Cancer at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments.

The company has the passion and determination to develop new medicines that help improve and extend the lives of people living with cancer. Prostate cancer is the second most commonly diagnosed cancer in men and a key area of focus for Bayer.

The company’s franchise includes two products on the market (Nubeqa™ and Xofigo™) and several compounds in development, including a unique approach of advancing targeted alpha therapies.

Bayer is focused on addressing the unique needs of prostate cancer patients, providing treatments that extend their lives throughout the different stages of the disease and allowing them to continue their everyday activities, so that they can live longer, better lives.”

https://www.bayer.com/media/en-us/nubeqa-darolutamide-receives-eu-approval-for-additional-indication-in-prostate-cancer/

AstraZeneca and Daiichi Sankyo’s Enhertu met prespecified criteria for objective response rate and duration of response

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AstraZeneca and Daiichi Sankyo’s Enhertu met prespecified criteria for objective response rate and duration of response

March 06, 2023: “Positive high-level results from an analysis of the ongoing DESTINY-PanTumor02 Phase II trial showed AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) met the prespecified target for objective response rate (ORR) and demonstrated durable response across multiple HER2-expressing advanced solid tumours in heavily pretreated patients.

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The DESTINY-PanTumor02 Phase II trial is evaluating the efficacy and safety of Enhertu in patients with locally advanced, unresectable, or metastatic previously treated, HER2-expressing solid tumours not eligible for curative therapy, including biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and rare cancers.

The primary endpoint of the trial is investigator-assessed confirmed ORR and investigator-assessed duration of response (DoR) is a key secondary endpoint.

The data will be presented at an upcoming medical meeting and shared with global regulatory authorities.

HER2 is a tyrosine kinase receptor protein expressed on the surface of various tissue cells throughout the body and is involved in normal cell growth.

In some cancer cells, HER2 expression is amplified or the cells have activating mutations.

While HER2-directed therapies have been used to treat breast, gastric and lung cancers, more research is needed evaluating their potential role in treating other HER2-expressing tumour types.

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said, “Enhertu has already demonstrated its potential to improve outcomes for patients with HER2-targetable breast, gastric and lung cancers, and these positive initial results in other tumour settings with significant unmet need are very encouraging.

The DESTINY-PanTumor02 results mark an important step forward in our understanding of the potential role of Enhertu across multiple HER2-expressing tumour types.”

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said, “The clinically meaningful responses seen in the DESTINY-PanTumor02 trial reaffirm our belief in the potential of Enhertu across multiple HER2-expressing cancers.

The results seen so far across multiple cohorts of the trial will inform next steps of our broad development programme as we look to bring this important medicine to as many patients as quickly as possible.”

The safety profile observed in patients treated with Enhertu in the DESTINY-PanTumor02 trial was consistent with that seen in other trials of Enhertu with no new safety signals identified.​”

DESTINY-PanTumor02
DESTINY-PanTumor02 is a global, multicentre, multi-cohort, open-label Phase II trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) for the treatment of HER2-expressing tumours, including biliary tract cancer, bladder cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer and rare tumours.

The primary efficacy endpoint of DESTINY-PanTumor02 is confirmed ORR as assessed by investigator. Secondary endpoints include DoR, disease control rate, progression-free survival, overall survival, safety, tolerability and pharmacokinetics.

DESTINY-PanTumor02 has enrolled 268 patients at multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. 

Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in more than 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-low (immunohistochemistry [IHC] 1+ or IHC 2+/in-situ hybridisation [ISH]-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 trial.

Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial and/or DESTINY-Gastric02 trial.

Enhertu development programme
A comprehensive global development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers.

Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.”

https://www.astrazeneca.com/media-centre/press-releases/2023/enhertu-destiny-pantumor02-shows-positive-results.html

FDA Outlines Steps to Strengthen Tobacco Program

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FDA Outlines Steps to Strengthen Tobacco Program

February 24, 2023: “The U.S. FDA’s Center for Tobacco Products (CTP) outlined the steps it plans to take in response to an external evaluationExternal Link Disclaimer I commissioned last year from an independent panel of evaluators working through the Reagan-Udall Foundation.

The evaluation was an important opportunity to take a critical look at the Tobacco Program’s regulatory processes and operations.We have made tremendous progress preventing death and disability caused by tobacco use, but I am a strong believer that we can always benefit from examining how we can work most effectively and proactively to protect public health, support our staff, and be as responsive as possible to external stakeholders.

When I started my career in intensive cardiac care, hospitals were full of relatively young people with sudden death, heart attacks, strokes and cancer attributable to tobacco use.

The effectiveness of the public health and medical communities to reduce the toll of tobacco products was enhanced when the FDA was granted the authority to regulate tobacco. 

As we enter this era of declining use of combustible tobacco and continued innovation in the e-cigarette industry, the societal concerns are not subtle.

Our ability to keep pace with these changes will depend on immediate, short-term and long-term actions the center is taking that we believe will position the agency to more successfully implement our regulatory oversight of tobacco products. 

CTP Director Brian King, Ph.D., M.P.H., has provided more detail about our approach to respond to the evaluation recommendations and our new plans, which will include the release of a 5-year strategic plan and comprehensive policy agenda by the end of the year.

CTP has committed to providing regular updates on the progress of these activities, including some noted here.

Application Review

In the past several years in particular, CTP has made important progress in the review of applications for e-cigarette products – authorizing several tobacco-flavored e-cigarette products and devices and rejecting marketing applications for millions of products that did not meet the requirements in the law.

Given the ever-evolving tobacco marketplace, it is imperative that we optimize the framework for application reviews to ensure any products marketed meet the law’s public health and regulatory standards.

This work will include, among other things: 

  • further streamlining of reviews when appropriate; 
  • increasing the use of the Tobacco Products Scientific Advisory Committee to discuss broader scientific matters central to premarket evaluation and individual product applications; 
  • posting current and future scientific policy memos and reviewer guides when appropriate; and
  • working internally and through engagement with external stakeholders to better communicate on scientific issues and practices to support efficiency, effectiveness, and transparency. These critical efforts will be bolstered by a new director in CTP’s Office of Science, who will begin in late March.

To achieve these goals, we need to have the appropriate resources to hire and retain staff with the skills needed to effectively meet our public health mandate around tobacco.

Since the agency’s fiscal year 2020 budget request, the FDA has advocated for the authority to collect user fees from e-cigarette companies, which currently do not pay user fees despite the enormous workload to review and make decisions regarding these products.

The FDA also continues to explore ways, including engaging with the U.S. Department of Health and Human Services and the Office of Personnel Management, to identify solutions to facilitate more timely and efficient hiring of qualified and diverse professionals that match CTP’s needs.  

Compliance and Enforcement

As the agency continues to make progress on its review of new and pending applications for novel products like e-cigarettes, the FDA will take additional action to remove illegal products from the market—particularly ones that have led to e-cigarettes being the most commonly used tobacco product among youth.

Between January 2021 and February 17, 2023, the FDA has issued more than 550 warning letters to companies for continuing to sell e-cigarette products that lacked the required FDA marketing authorization.

These companies had millions of products listed with the FDA. After receiving warning letters, a majority of these companies have complied and removed their products from the market. However, in cases where companies did not do so, the FDA can pursue further enforcement action.

For example, the FDA recently worked with the Department of Justice (DOJ) to file the first complaints for permanent injunctions against six e-cigarette manufacturers.

Additionally, for the first time, the FDA this week filed civil money penalty complaints against four tobacco product manufacturers for manufacturing and selling new e-liquids without marketing authorization.

The agency will continue to work as expeditiously as possible to remove illegal products from the market while identifying new ways to strengthen compliance and enforcement.  

As recommended by the external evaluation, effective immediately, the FDA will begin planning to convene a summit with senior officials from the HHS and DOJ related to enforcement.

The agency will also continue to work with other government agencies, such as U.S. Customs and Border Protection, the U.S. Postal Service, the Federal Trade Commission, Bureau of Alcohol, Tobacco, Firearms and Explosives, as well as with our compliance and enforcement partners at the state/local/territorial/tribal levels.”

This work will maximize compliance and enforcement activities where there are shared interests. Additionally, the FDA will explore alternative approaches to achieve compliance outside of judicial enforcement actions.”

https://www.fda.gov/news-events/press-announcements/fda-outlines-steps-strengthen-tobacco-program

AZ’s acquisition with CinCor Pharma completed

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AZ’s acquisition with CinCor Pharma completed

February 24, 2023: “AstraZeneca announced the successful completion of the acquisition of CinCor Pharma, Inc. (CinCor), a US-based clinical-stage biopharmaceutical company, focused on developing novel treatments for resistant and uncontrolled hypertension as well as chronic kidney disease.

The acquisition bolsters AstraZeneca’s cardiorenal pipeline by adding baxdrostat (CIN-107), an aldosterone synthase inhibitor (ASI) for blood pressure lowering in treatment-resistant hypertension, to its cardiorenal portfolio.

Baxdrostat represents a potentially leading next-generation ASI as it is highly selective for aldosterone synthase and spares the cortisol pathway in humans.

The opportunity also brings the potential for combination with Farxiga and complements AstraZeneca’s strategy to provide added benefit across cardiorenal diseases, where there is a high unmet medical need.

The acquisition was completed through a tender offer to purchase all outstanding shares of CinCor for approximately $1.3bn upfront.

As part of the transaction, AstraZeneca acquired the cash and marketable securities on CinCor’s balance sheet, which totalled approximately $500 million as of the closing, excluding transaction-related expenses. Under the terms of the agreement, CinCor shareholders also received a non-tradable contingent value right, payable upon a specified regulatory submission of a baxdrostat product.

Combined, the upfront and contingent value payments represent, if achieved, a transaction value of approximately $1.8bn.

As of the expiration of the tender offer, 39,580,275 shares of CinCor were validly tendered and not validly withdrawn from the tender offer, representing approximately 86.3% of the outstanding shares of common stock of CinCor, and such shares have been accepted for payment in accordance with the terms of the tender offer.

CinCor’s shares will be delisted from the Nasdaq Stock Market, and CinCor will terminate its registration under the U.S. Securities Exchange Act of 1934 as soon as practicable following completion of the acquisition.

Forward-looking statements
This announcement may include statements that are not statements of historical fact, or “forward-looking statements,” including with respect to AstraZeneca’s acquisition of CinCor.

Such forward-looking statements include, but are not limited to, AstraZeneca’s and CinCor’s beliefs and expectations and statements about the benefits sought to be achieved in AstraZeneca’s acquisition of CinCor, the potential effects of the acquisition on both AstraZeneca and CinCor, as well as the expected benefits and success of baxdrostat and any combination product.

These statements are based upon the current beliefs and expectations of AstraZeneca’s and CinCor’s management and are subject to significant risks and uncertainties.

There can be no guarantees that baxdrostat or any combination product will receive the necessary regulatory approvals or prove to be commercially successful if approved.

If underlying assumptions prove inaccurate or risks or uncertainties materialise, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, the possibility that the milestone related to the contingent value right will not be achieved; general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of COVID-19; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; competition from other products; and challenges inherent in new product development, including obtaining regulatory approval.

Neither AstraZeneca nor CinCor undertakes any obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise, except to the extent required by law.

Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in AstraZeneca’s Annual Report on Form 20-F for the year ended 31 December 2022, CinCor’s Annual Report on Form 10-K for the year ended 31 December 2021 and CinCor’s Quarterly Reports on Form 10-Q for the three months ended 31 March 2022, 30 June 2022 and 30 September 2022, in each case as amended by any subsequent filings made with the SEC. 

https://www.astrazeneca.com/media-centre/press-releases/2023/astrazeneca-acquires-cincor-for-cardiorenal-asset.html

Pfizer’s Elranatamab Receives FDA and EMA Filing Acceptance

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Pfizer’s Elranatamab Receives FDA and EMA Filing Acceptance

February 22, 2023: “Pfizer Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Priority Review for the company’s Biologics License Application (BLA) for elranatamab, an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (BsAb), for the treatment of patients with relapsed or refractory multiple myeloma (RRMM).

Priority Review is intended to direct attention and resources from regulatory authorities toward drugs that, if approved, could offer significant improvements over existing options for serious conditions in order to make these drugs available to patients faster.

The FDA’s decision on the application is expected in 2023. The European Medicines Agency (EMA) has also accepted elranatamab’s marketing authorization application (MAA).

The company is working closely with the EMA to facilitate their review and will provide updates on timing as appropriate.

“Today, multiple myeloma is a fatal hematologic malignancy, with a median survival of just over five years. As an off-the-shelf treatment, BCMA bispecific antibodies are heralding a new treatment paradigm that can greatly impact the lives of people with this disease.” said Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology and Rare Disease, Pfizer Global Product Development.

“We believe that elranatamab, if approved, has the potential to become the next standard of care for multiple myeloma given its favorable clinical results and convenient subcutaneous route of administration.

We look forward to working with the FDA and EMA to bring this new innovative medicine to patients globally.”

Elranatamab is designed to bind to BCMA, which is highly expressed on the surface of multiple myeloma (MM) cells, and CD3 receptors found on the surface of T-cells, bridging them together and activating the T-cells to kill the myeloma cells.

The BLA and MAA for elranatamab are primarily based on data from cohort A (BCMA-naïve – n=123) of MagnetisMM-3 (NCT04649359), an ongoing, open-label, multicenter, single-arm, Phase 2 study designed to evaluate the safety and efficacy of elranatamab monotherapy in patients with RRMM.

Enrolled patients represent a heavily pretreated population, who previously received at least three classes of therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

With a median follow up of 10.4 months, patients who received elranatamab as their first BCMA-targeted therapy achieved a high objective response rate of 61% (55% had a very good partial response rate or better), with an 84% probability of maintaining the response at nine months.

The MagnetisMM-3 results also suggest elranatamab has a manageable safety profile. The two-step-up priming dose regimen (12/32 mg) helped mitigate the rate and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) among the 119 patients in cohort A who were treated with this priming regimen.

All cases of CRS were Grade 1 or 2 and the majority occurred after the first (43% of patients) or second (24% of patients) dose, with only 6% of patients experiencing CRS after dose 3 and fewer than 1% experiencing CRS after dose 4.

Observed cases of ICANS (3%) were neither common nor severe (Grade 1/2 only were reported). No fatal neurotoxicity events were observed.

These data were presented at the 64th American Society of Hematology Annual Meeting and Exposition in December 2022.

This study is part of the MagnetisMM clinical research program that expands to additional patient populations over time, with ongoing registrational-intent trials that explore elranatamab both as monotherapy and in combination with standard or novel therapies, spanning multiple patient populations, from newly diagnosed MM to RRMM.

This includes MagnetisMM-5 (NCT05020236) in the double class exposed setting, MagnetisMM-6 (NCT05623020) in transplant ineligible newly diagnosed patients, and MagnetisMM-7 (NCT05317416) as maintenance treatment in newly diagnosed patients after transplant, all of which are currently enrolling.

In November 2022, Pfizer announced that elranatamab was granted Breakthrough Therapy Designation by the FDA.

In addition, elranatamab has been granted Orphan Drug Designation by the FDA and the EMA for the treatment of MM.

The FDA and EMA have also granted elranatamab Fast Track Designation and the PRIME scheme, respectively, for the treatment of patients with RRMM.

The UK Medicines and Healthcare Products Regulatory Agency (MHRA) has granted elranatamab Innovative Medicine Designation and the Innovation Passport for the treatment of MM.

The FDA has accepted elranatamab for Project ORBIS, which is a framework for the concurrent submission and review of oncology products to potentially expedite approvals in certain countries outside of the US; currently 5 countries (Switzerland, Brazil, Canada, Australia, and Singapore) have accepted to participate.

About Elranatamab

Elranatamab is an investigational, off-the-shelf, humanized BCMA CD3-targeted BsAb. BsAbs are a novel form of cancer immunotherapy that bind to and engage two different targets at once. One arm binds directly to specific antigens on cancer cells and the other arm binds to T-cells, bringing both cell types together.

The binding affinity of elranatamab for BCMA and CD3 has been engineered to elicit potent T-cell-mediated anti-myeloma activity. Elranatamab is administered subcutaneously, which offers more convenience over intravenous administration.

About MagnetisMM-3

MagnetisMM-3 (NCT04649359) is an ongoing, open-label, multicenter, single-arm, Phase 2 study designed to evaluate the safety and efficacy of elranatamab monotherapy in patients with RRMM.

Patients received subcutaneous (SC) elranatamab 76 mg weekly (QW) on a 28-day cycle with a step-up priming dose regimen, wherein 12 mg and 32 mg are administered on Day 1 and Day 4, respectively, during Cycle 1.

For patients receiving 6 or more cycles and achieving a partial response or better for at least 2 months, the dosing interval was once every two weeks (Q2W).

About Multiple Myeloma

MM is a blood cancer that affects plasma cells made in the bone marrow. Healthy plasma cells make antibodies that help the body fight infection.

There are over 34,000 new cases of MM diagnosed annually in the U.S. and 176,000 globally.

Despite treatment advances, there is currently no cure. The median survival is just over five years, and most patients receive four or more lines of therapy.”

https://www.pfizer.com/news/press-release/press-release-detail/pfizers-elranatamab-receives-fda-and-ema-filing-acceptance

FDA Provides Draft Labeling Recommendations for Plant-based Milk Alternatives to Inform Consumers

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FDA Provides Draft Labeling Recommendations for Plant-based Milk Alternatives to Inform Consumers

February 22, 2023: “The U.S. FDA announced draft recommendations for industry on the naming of plant-based foods that are marketed and sold as alternatives to milk.

The draft guidance also recommends voluntary nutrient statements for the labeling of some plant-based milk alternatives. 

“Today’s draft guidance was developed to help address the significant increase in plant-based milk alternative products that we have seen become available in the marketplace over the past decade,” said FDA Commissioner Robert M. Califf, M.D.

“The draft recommendations issued today should lead to providing consumers with clear labeling to give them the information they need to make informed nutrition and purchasing decisions on the products they buy for themselves and their families.” 

In addition to the increase in market availability and consumption, the variety of alternative products available in the marketplace has also greatly expanded from soy, rice and almond to include cashew, coconut, flaxseed, hazelnut, hemp seed, macadamia nut, oat, pea, peanut, pecan, quinoa and walnut-based beverages. Although these products are made from liquid-based extracts of plant materials, such as tree nuts, legumes, seeds or grains, they are frequently labeled with names that include the term “milk.”
 
The draft guidance, “Labeling of Plant-based Milk Alternatives and Voluntary Nutrient Statements: Guidance for Industry,” recommends that a plant-based milk alternative product that includes the term “milk” in its name (e.g., “soy milk” or “almond milk”), and that has a nutrient composition that is different than milk, include a voluntary nutrient statement that conveys how the product compares with milk based on the U.S. Department of Agriculture’s (USDA) Food and Nutrition Service fluid milk substitutes nutrient criteria.

For example, the label could say, “Contains lower amounts of Vitamin D and calcium than milk.” 

In September 2018, the FDA requested information on the labeling of plant-based milk alternatives (PBMA) with terms that include the names of dairy foods such as “milk.”

More than 13,000 comments were received, and the FDA determined that consumers generally understand that PBMA do not contain milk and choose to purchase PBMA because they are not milk.

However, many consumers may not be aware of the nutritional differences between milk and PBMA products.

For example, almond- or oat-based PBMA products may contain calcium and be consumed as a source of calcium, but their overall nutritional content is not similar to milk and fortified soy beverages, and they are not included as part of the dairy group in the Dietary Guidelines 2020-2025.

Dairy foods, including milk, are recommended by the Dietary Guidelines as part of a healthy eating pattern and contribute multiple key nutrients, including protein and vitamins A and B-12, along with calcium, potassium and vitamin D, which are currently under-consumed.

The Dietary Guidelines only includes fortified soy beverages in the dairy group because their nutrient composition is similar to that of milk.

However, the nutritional composition of PBMA products varies widely within and across types, and many PBMAs do not contain the same levels of key nutrients as milk. 

“Getting enough of the nutrients in milk and fortified soy beverages is especially important to help children grow and develop, and parents and caregivers should know that many plant-based alternatives do not have the same nutrients as milk,” said Susan T. Mayne, Ph.D., director of the FDA’s Center for Food Safety and Applied Nutrition.

“Food labels are an important way to help support consumer behavior, so we encourage the use of the voluntary nutritional statements to better help customers make informed decisions.” 

To support consistency across federal nutrition policies, the draft guidance recommends that industry use the USDA’s Food and Nutrition Service fluid milk substitutes nutrient criteria to determine if a PBMA is nutritionally similar to milk.

Also, the FDA encourages consumers to use the Nutrition Facts label to compare the nutrient content of different products to help make informed choices.

The FDA is accepting comments on the draft guidance. A manufacturer may choose to implement the recommendations in a draft guidance before the guidance becomes final.

Labels provide consumers with valuable information to help choose healthier foods.

It is one of the priorities of the FDA’s nutrition efforts to ensure people in the U.S. have greater access to healthier foods and nutrition information to help make healthy choices more easily.

The draft guidance issued today does not apply to other plant-based dairy alternatives, such as plant-based cheese or yogurt alternatives.

The FDA is in the process of developing a draft guidance to address the labeling and naming of other plant-based alternative products and will communicate updates when available.”

https://www.fda.gov/news-events/press-announcements/fda-provides-draft-labeling-recommendations-plant-based-milk-alternatives-inform-consumers

FDA Files Civil Money Penalty Complaints Against Four E-Cigarette Product Manufacturers

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FDA Files Civil Money Penalty Complaints Against Four E-Cigarette Product Manufacturers

February 22, 2023: “The U.S. FDA announced it has filed civil money penalty (CMP) complaints against four tobacco product manufacturers for manufacturing and selling e-liquids without marketing authorization.

This is the first time the FDA has filed CMP complaints against tobacco product manufacturers to enforce the Federal Food, Drug, and Cosmetic (FD&C) Act’s premarket review requirements for new tobacco products.

It is illegal to manufacture, sell, or distribute e-liquids that the FDA has not authorized.

The FDA previously warned each of the companies that, by making and selling their e-liquids without marketing authorization from the FDA, they were in violation of the FDA’s premarket requirements for tobacco products and that failure to correct these violations could lead to an enforcement action, such as a CMP.

Despite the agency’s warning, these companies continue to make and sell their unauthorized e-liquids to consumers. 

“Holding manufacturers accountable for making or selling illegal tobacco products is a top priority for the FDA,” said Brian King, Ph.D., M.P.H., director of the FDA’s Center for Tobacco Products.

“We are prepared to use the full scope of our authorities to enforce the law—especially against those who have continued to violate the law after being warned by the agency.” 

As of Feb. 21, the FDA has filed CMP complaints against the following four manufacturers:

  • BAM Group LLC doing business as VapEscape
  • Great American Vapes LLC doing business as Great American Vapes
  • The Vapor Corner Inc. doing business as Vapor Corner Inc., The Vapor Corner, and Vapor Corner
  • 13 Vapor Co. LLC doing business as 13 Vapor

Currently, under the FD&C Act, the maximum CMP amount is $19,192 for a single violation relating to tobacco products. The FDA typically seeks the statutory maximum allowed by law and is doing so in these four cases.

The companies the FDA has filed CMP complaints against can pay the penalty, enter into a settlement agreement, request an extension of time to file an answer to the complaint, or file an answer and request a hearing.

Companies that do not take action within 30 days after receiving the complaint risk a default order imposing the full penalty amount.  

“These latest enforcement activities are part of a comprehensive approach to actively identify violations and to deter illegal conduct,” said Dr. King. “These actions should be a wakeup call that all tobacco product manufacturers—big or small—are required to obey the law.”    

All new tobacco products, including all e-cigarettes, on the market without the statutorily required premarket authorization are marketed illegally and are subject to FDA enforcement action.

The FDA closely monitors manufacturer compliance with the law and may take action when violations occur. Between Jan. 2021 through Feb. 17, 2023, the FDA has issued more than 550 warning letters to firms—both large and small—for manufacturing, selling, and/or distributing new tobacco products without marketing authorization from the FDA.

After receiving warning letters, a majority of these companies have complied and removed their products from the market. Manufacturers that continue to violate the law risk subsequent enforcement.

In addition to CMPs, the agency also has authority to take other enforcement action, as appropriate, including seizures, injunctions, and criminal prosecutions.   

Manufacturers must submit a marketing application to the FDA and receive authorization to legally sell a new tobacco product in the United States.

The FDA encourages manufacturers to learn more about the three pathways to submit an application for new tobacco products.”

https://www.fda.gov/news-events/press-announcements/fda-files-civil-money-penalty-complaints-against-four-e-cigarette-product-manufacturers

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