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FDA Grants Fast Track Designation For Omecamtiv Mecarbil In Heart Failure

May 8, 2020: “Amgen and Cytokinetics, Incorporated announced that the U.S.FDA has granted Fast Track designation for omecamtiv mecarbil, a novel selective cardiac myosin activator, also known as a cardiac myotrope, being developed for the potential treatment of chronic heart failure with reduced ejection fraction (HFrEF).

Fast Track designation may potentially expedite the review of a drug that is intended for the treatment of a serious or life-threatening disease or condition and demonstrates the potential to address an unmet medical need for such a disease or condition.

“This Fast Track designation represents an important milestone in the development of omecamtiv mecarbil,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. 

“Today, half of heart failure patients will die within five years of diagnosis, underscoring the urgent need for new therapies for this grievous condition.”

“We are pleased that the FDA has granted Fast Track designation for omecamtiv mecarbil for the potential treatment of heart failure,” said Robert I. Blum, president and chief executive officer of Cytokinetics.

“The prevalence of heart failure is growing with our aging demographics, and GALACTIC-HF is designed to assess the clinical effects of our novel myosin activator in patients meaningfully at risk.”

GALACTIC-HF (Global Approach to Lowering Adverse Cardiac

Outcomes Through Improving Contractility in Heart Failure), one of the largest Phase 3 global cardiovascular (CV) outcomes studies in heart failure ever conducted, is designed to evaluate whether treatment with omecamtiv mecarbil, when added to standard of care, reduces the risk of heart failure events (heart failure hospitalization and other urgent treatment for heart failure) and CV death in patients with HFrEF. 

GALACTIC-HF enrolled 8,256 patients in 35 countries who were either hospitalized at the time of enrollment for a primary reason of heart failure or had a hospitalization or admission to an emergency room for heart failure within one year prior to screening. 

Dose selection for omecamtiv mecarbil in this study uses a blood test. Top-line results from GALACTIC-HF are expected in Q4 2020.

About Omecamtiv Mecarbil and the Phase 3 Clinical Trials Program

Omecamtiv mecarbil is a novel, selective cardiac myosin activator, also known as a cardiac myotrope, that binds to the catalytic domain of myosin.

Preclinical research has shown that omecamtiv mecarbil increases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption.

Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting chemical energy into the mechanical force resulting in cardiac contraction. 

Omecamtiv mecarbil is being developed for the potential treatment of heart failure with reduced ejection fraction (HFrEF) under a collaboration between Amgen and Cytokinetics, with funding and strategic support from Servier.

Omecamtiv mecarbil is the subject of a comprehensive Phase 3 clinical trials program composed of GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), a Phase 3 clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on CV outcomes and METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure), a Phase 3 clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity.

About Cytokinetics and Amgen Collaboration

In 2006, Cytokinetics and Amgen entered into a strategic alliance to discover, develop and commercialize novel small molecule therapeutics designed to activate the cardiac sarcomere for the potential treatment of heart failure.

Omecamtiv mecarbil is being developed by Amgen in collaboration with Cytokinetics, with funding and strategic support from Servier. Amgen holds an exclusive, worldwide license to omecamtiv mecarbil and related compounds, subject to Cytokinetics’ specified development and commercialization rights. 

Cytokinetics is eligible for pre-commercialization and commercialization milestone payments and royalties that escalate based on increasing levels of annual net sales of products commercialized under the agreement.

Cytokinetics has co-invested with Amgen in the Phase 3 development program of omecamtiv mecarbil in exchange for increased royalties from Amgen on worldwide sales of omecamtiv mecarbil outside Japan and co-promotion rights in institutional care settings in North America. 

 Amgen has also entered an alliance with Servier for exclusive commercialization rights for omecamtiv mecarbil in Europe as well as the Commonwealth of Independent States, including Russia. 

Servier contributes funding for development and provides strategic support to the program.”

https://www.amgen.com/media/news-releases/2020/05/fda-grants-fast-track-designation-for-omecamtiv-mecarbil-in-heart-failure/

CDC scientists honored as 2020 Service to America Medal Finalists

May 08, 2020: “Centers for Disease Control and Prevention Control (CDC) scientists Dr. Vikram Krishnasamy, and Dr. Peter Briss and the 2019 Lung Injury Prevention Team, have been named finalists in the Partnership for Public Service’s annual Service to America awards.

The awards, named after Partnership founder Samuel J. Heyman and known as the “Sammies,” recognize the talents and achievements of federal employees.

This is the third year in a row that one or more CDC employees have been honored as finalists. The winners will be announced in the fall.

“CDC is proud that Dr. Briss and his team and Dr. Krishnasamy are being recognized across the federal government for their extraordinary work,” said CDC Director Robert R. Redfield, MD.

“Their commitment to excellence and innovation while addressing two of the most significant public health issues of our time is a true testament to public health service.”

Peter Briss, MD, MPH, is the director of the Office of Medicine and Science in CDC’s National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), as well as the center’s medical director.

He and the 2019 Lung Injury Prevention Team are being recognized for their work in 2019 “identifying the chemical compound in e-cigarette or vaping, products that caused life-threatening lung injuries predominately among young adults, communicating the danger to public health and saving lives.”

Prior to this discovery, it was unclear what caused e-cigarette, or vaping, associated lung injury (EVALI).

Dr. Briss and the EVALI team were able to identify the major culprit from tiny amounts of the compound recovered from patients’ lungs. This work led to a sharp decrease in emergency room visits and deaths for EVALI.

The team included Dr. Briss, who led the effort and focused it on the crucial scientific questions that needed answers; Dana Meaney-Delman, MD, MPH, who put together CDC response teams and coordinated with local and state partners; and Chris Jones, PhD, who moved the team’s short-term activities into long-term programs. Hundreds of other CDC staff also made major contributions.

Vikram Krishnasamy, MD, MPH, is an innovative leader in the fight against opioid addiction in the United States. He is a senior medical officer in CDC’s National Center for Injury Prevention and Control and is nominated for his work in CDC’s response to the opioid overdose epidemic.

A member of CDC’s Opioid Response Coordination Unit since 2018, Dr. Krishnasamy established a training program and communications network to help local public health officials address the opioid overdose epidemic.

His work has led to the training of more than 1,000 CDC employees and US Public Health Service officers from other agencies who now have both basic knowledge about the opioid epidemic and the skill sets needed to support local and state health departments.

He continues to lead opioid-related initiatives across CDC, coordinating emergency response needs and working with funded partners.

In 2019, more than 60 medical professionals in six states were arrested for illegally prescribing and distributing opioids.

In a first-ever federal coordination between law enforcement and public health officials, Dr. Krishnasamy led a team that focused on ensuring that patients dependent on pain medications and left without medical care could be directed to legitimate professionals and addiction treatment providers.

The Partnership for Public Service, a non-partisan non-profit, has sponsored the awards and campaign for the last 19 years.

The program has honored more than 500 outstanding federal employees since its inception in 2002. This year there are 27 finalists from 11 cabinet agencies and their operating divisions.”

https://www.cdc.gov/media/releases/2020/p0507-2020-service-medal-finalists-honored.html

Gilead Announces Approval of Veklury® (remdesivir) in Japan

May 7, 2020: “Gilead Sciences, Inc. announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted regulatory approval of Veklury® (remdesivir) as a treatment for SARS-CoV-2 infection, the virus that causes COVID-19, under an exceptional approval pathway.

The exceptional approval was granted due to the COVID-19 pandemic and references the Emergency Use Authorization of remdesivir in the United States.

The approval is based on clinical data from the U.S. National Institute of Allergy and Infectious Diseases’ global Phase 3 trial, Gilead’s Phase 3 SIMPLE trial in patients with severe manifestations of COVID-19, and available data from Gilead’s compassionate use program, including patients in Japan.

“The Japanese approval of remdesivir is in recognition of the urgent need to treat critically ill patients in Japan. It is a reflection of the exceptional circumstances of this pandemic,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences.

“We thank the Japanese Ministry of Health, Labour and Welfare for their leadership and collaboration, as we together work to respond to this public health emergency.”

Due to the current public health emergency, the U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization for remdesivir for the treatment of COVID-19.

In the United States, remdesivir is an investigational drug that has not been approved by the FDA for any use, and the safety and efficacy of remdesivir for the treatment of COVID-19 has not been established.

The distribution of remdesivir in the United States has been authorized only for the treatment of hospitalized patients with severe COVID-19; please see below for additional important information about the authorized use of remdesivir in the United States.

Remdesivir is not yet licensed or approved outside of Japan and ongoing clinical trials continue to evaluate its safety and efficacy. Gilead continues to work with global regulatory authorities to ensure appropriate access to remdesivir.

Remdesivir is an investigational nucleotide analog with broad-spectrum antiviral activity both in vitro and in vivo in animal models against multiple emerging viral pathogens, including Ebola, Marburg, MERS and SARS. In vitro testing conducted by Gilead has demonstrated that remdesivir is active against the virus that causes COVID-19.

The safety and efficacy of remdesivir to treat COVID-19 are being evaluated in multiple ongoing Phase 3 clinical trials.”

gilead.com/news-and-press/press-room/press-releases/2020/5/gilead-announces-approval-of-veklury-remdesivir-in-japan-for-patients-with-severe-covid19

Preliminary positive results seen for microbiome-based C. diff treatment

May 07, 2020: “A new microbiome-based treatment for Clostridioides difficile infection showed success in reducing recurrence of the infection at 8 weeks, according to preliminary results released by the manufacturer.

“With RBX2660 and other microbiome restoration therapies, the things that are most exciting about these therapies is that we will finally be able to offer a standardized product and therapy to our patients,” Sahil Khanna, MBBS,of Mayo Clinic, told Healio Gastroenterology and Liver Disease.

“RBX2660 is distinct from other therapies in several ways. One, it’s standardized. … Two, it’s a non-invasive, enema-based therapy so patients don’t need a bowel preparation. Patients don’t need to have anesthesia, no need for sedation or a colonoscopy.”

RBX2660 (Rebiotix/Ferring Pharmaceuticals) is a live biotherapeutic that is designed to “help restore the gut microbiome community,” according to the press release.

The primary endpoint of the phase 3 randomized, multicenter, double-blinded, placebo-controlled study, which is still ongoing, is recurrence of CDI at 8 weeks.

According to the manufacturer, “RBX2660 showed statistically significant success over placebo meeting the preliminary primary efficacy endpoint.”

“What is most exciting is that RBX2660 is the first FMT product used to prevent recurrence of C. difficile to meet its primary clinical end-point in both phase 2 and phase 3 clinical trials.

This speaks to the efficacy of this product and the robust nature of the data to support its usage, if approved by the FDA,” Paul Feuerstadt, MD, FACG, AGAF, of Gastroenterology Center of Connecticut, told Healio via email.

“If RBX2660 is reviewed by the FDA and approved, this treatment will be much more widely available to many practitioners who did not have access to FMT previously or did not feel comfortable with the data to support FMT when there was not an FDA-approved formulation.

With epidemiologic trends showing more and more patients having multiple recurrences of C. difficile, RBX2660, as a form of fecal transplantation, will likely move earlier in the treatment algorithm for many more providers.

This should prevent patients from having multiple recurrences thereby decreasing the massive burden of this infection on our healthcare system.”

The data are not yet unblinded while the safety follow-up is conducted, but the finalized data are expected in the second half of the year, a Rebiotix and Ferring Pharmaceuticals representative said.”

“C. diff infection is a significant public health threat that has limited treatment options.

These positive preliminary findings represent a major step forward toward bringing an innovative, non-antibiotic option to patients that may help restore their gut microbiome,” Per Falk, Ferring’s President and Chief Science Officer, said in the press release.

“With health systems under increasing pressure due to viruses like COVID-19 and the rising threat of antimicrobial resistance, the need for new therapies is greater than ever.”

https://www.healio.com/gastroenterology/infection/news/online/%7B1aeee13e-381e-4d68-aa0e-bf2bf231b0c2%7D/preliminary-positive-results-seen-for-microbiome-based-c-diff-treatment

Imperial College volunteers find innovative ‘Hackspace’ solution

May 05, 2020: “Volunteers at Imperial College London are making more than 50,000 disposable visors for Imperial College Healthcare NHS Trust hospitals.
In partnership with the Trust and our infection prevention and control (IPC) team, the project is led by Imperial’s Advanced Hackspace, which is designed to facilitate collaboration, innovation and experimentation, and the NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance.

The Trust IPC team have worked closely with the Hackspace team to develop, optimise and evaluate the visors, ensuring they are of the highest quality and therefore safe and appropriate for use. The project will help to ensure a sustainable and ongoing supply of equipment for Trust staff as part of the continuing response to coronavirus. 

Dr Bob Klaber, director of strategy, research and innovation at the Trust said: ‘The amazing spirit of innovation, volunteering and collaboration between Imperial College and the Trust has produced a very high-quality piece of personal protective equipment at a significant scale and outstanding value.

This innovative engineering-led project has certainly provided us with a sustainable local supply chain that we can continue to develop in order to help with our ongoing response to the coronavirus pandemic.’

Professor Alison Holmes, Director of Infection Control at the Trust and Director of the NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at said: ‘This project is an outstanding example of collaborative working across Imperial College London and the Trust to increase supplies of critical PPE.’

More than 6,500 have already been delivered to Charing Cross Hospital and tens of thousands more will be distributed across Trust hospitals in the coming weeks.

They will be in use across all five hospital sites, delivered via the central operations team, who look after the supply and distribution of PPE across the Trust.

An entire floor of Imperial College London’s Translation & Innovation Hub (I-HUB) in White City has been converted to allow a small group of volunteers to safely assemble the visors whilst recognising social distancing guidelines.

Materials for the assembly of the first 7,000 visors were provided by Rolls Royce Motor Cars.

Professor Nick Jennings, Vice-Provost (Research and Enterprise) said: “This is a remarkable effort which shows the power of institutions coming together at a time of great need. It shows great speed of action and the willingness of volunteers to rally to a common cause.

Imperial has committed to doing all we can to help to respond to the pandemic, and I am proud to see our community and our NHS Trust colleagues rise so admirably to this challenge”

Head of Hackspace, Graham Hewson said, “The Advanced Hackspace team are well positioned to support this project, enterprising in their efforts to rapidly develop and assemble the early stage prototypes and plan for scaling.

I am extremely proud of all the team for their continued collaboration, hard work and dedication to this project.”

The demand for PPE during the coronavirus pandemic will continue as the NHS moves into the next phase of response and some urgent non-covid services start to resume.

Clinical and leadership teams at the Trust are currently reviewing a detailed set of recommended actions from NHS England and these include the provision of PPE.

https://www.imperial.nhs.uk/about-us/news/imperial-college-volunteers-supply-visors-for-the-trust

New data at the ASCO20 reflects Roche’s commitment to cancer care

May 07, 2020: “Roche announced that new data from clinical trials of 19 approved and investigational medicines across 21 cancer types, will be presented at the ASCO20 Virtual Scientific Program organised by the American Society of Clinical Oncology (ASCO), which will be held 29-31 May 2020.

A total of 120 abstracts that include a Roche medicine will be presented at this year’s meeting.

“At ASCO, we will present new data from many investigational and approved medicines across our broad oncology portfolio,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development.

“These efforts exemplify our long-standing commitment to improving outcomes for people with cancer, even during these unprecedented times.

By integrating our medicines and diagnostics together with advanced insights and novel platforms, Roche is uniquely positioned to deliver the healthcare solutions of the future.”

Together with its partners, Roche is pioneering a comprehensive approach to cancer care, combining new diagnostics and treatments with innovative, integrated data and access solutions for approved medicines that will both personalise and transform the outcomes of people affected by this deadly disease.

Key presentations
First results of tiragolumab, Roche’s novel cancer immunotherapy designed to bind to TIGIT, will be shared.

These results, from the phase II CITYSCAPE study, examine tiragolumab in combination with Tecentriq® (atezolizumab) compared with Tecentriq alone as an initial treatment for people with PD-L1-positive locally advanced unresectable or metastatic non-small cell lung cancer (NSCLC).

In addition, updated five-year overall survival rates with Alecensa® (alectinib) in people living with treatment-naive anaplastic lymphoma kinase (ALK)-positive metastatic/advanced NSCLC will be presented.

With five approved lung cancer medicines and an extensive pipeline across multiple subtypes, Roche’s ultimate aim is to provide an effective treatment option for each person diagnosed with the disease, tailored to the unique characteristics of their tumours.

Studies featured from partnerships with Flatiron Health and Foundation Medicine demonstrate how the use of next-generation sequencing (NGS) may help inform treatment decisions, optimise testing and enable personalised therapy, including an ongoing additional study designed to prospectively link longitudinal, real-world clinical data with genomic, imaging and outcomes data for patients with advanced lung cancers.

The study is monitoring circulating tumour DNA (ctDNA) using FoundationOne® Liquid, and tumour tissue samples will be genomically profiled using FoundationOne® CDx.

Based on this year’s virtual format, Roche will be launching a virtual newsroom for journalists to access further information on our contribution to the ASCO20 Virtual Scientific Program, as well as the latest innovations and developments in Roche’s approach to accelerating progress in cancer care.

The newsroom will be available on Friday 29 May, 08:00 CEST, and open to journalists from outside the United States.”

Overview of key presentations featuring Roche medicines at ASCO 2020

https://www.roche.com/media/releases/med-cor-2020-05-07.htm

FDA Continues to Combat Fraudulent COVID-19 Medical Products

May 07, 2020: “Today, the U.S. Food and Drug Administration is providing an update on the agency’s efforts to combat the extremely concerning actions by companies and individuals that are exploiting or taking advantage of widespread fear among consumers during the COVID-19 pandemic.

In response to scammers on the internet selling unproven medical products, the FDA has taken – and continues to take – a number of steps to find and stop those selling unapproved products that fraudulently claim to mitigate, prevent, treat, diagnose or cure COVID-19.

“While we seek to ensure access to critical medical products, it is imperative that we continue our efforts to find and prevent the sale and distribution of products that may be harmful to the public health.

Americans can rest assured that we’re leveraging our experience investigating, examining, and reviewing medical products, both at the border and within domestic commerce, to help ensure that the critical resources reaching the frontlines in the battle against COVID-19 are appropriate,” said FDA Associate Commissioner for Regulatory Affairs Judy McMeekin, Pharm.D.

“We take seriously our responsibility to determine whether the medical products coming into our country are fraudulent, counterfeit or illegitimate, and take action as needed.”

To date, the FDA has issued 42 warning letters to companies making bogus COVID-19 claims, including one to a seller of fraudulent chlorine dioxide products, equivalent to industrial bleach, frequently referred to as “Miracle Mineral Solution” or “MMS”, as a treatment for COVID-19.

After the seller refused to take corrective action, a federal court issued a preliminary injunction requiring the seller to immediately stop distributing its unproven and potentially dangerous product.

Additionally, as part of the FDA’s Operation Quack Hack, in just a few short weeks, the agency has discovered hundreds of such products including fraudulent drugs, testing kits and personal protective equipment (PPE) sold online with unproven claims.

We continue to work with online marketplaces, domain name registrars, payment processors and social media websites to remove from their platforms products that fraudulently claim to mitigate, prevent, treat, diagnose or cure COVID-19 and to keep those products from reappearing under different names.

At this time, the FDA has sent hundreds of abuse complaints to domain name registrars and internet marketplaces, who in most instances, have voluntarily removed the identified postings.

We will continue to monitor the online ecosystem for fraudulent products peddled by bad actors seeking to profit from this global pandemic. We encourage anyone aware of suspected fraudulent medical products for COVID-19 to report them to the FDA.

There are a number of examples of unproven products that the FDA is keeping out of the country.

Recently, the agency intercepted and investigated a case of mislabeled COVID-19 “treatment kits” offered for import.

As a result, Special Agents with the FDA’s Office of Criminal Investigations, with the help of domestic and international law enforcement counterparts in the United Kingdom, led the Department of Justice to bring a criminal complaint against a British man who sought to profit from this pandemic and jeopardize public health.

Until the curve is flattened, and even after, the FDA will continue to carry out the agency’s mission of protecting the health and safety of American consumers and strive to prevent unlawful FDA-regulated products from entering, or being distributed in, domestic commerce.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-continues-combat-fraudulent-covid-19-medical-products

Coronavirus (COVID-19) Update: Daily Roundup May 6, 2020

May 06, 2020: “The U.S. Food and Drug Administration today announced the following actions taken in its ongoing response effort to the COVID-19 pandemic:
  • Today, the FDA issued an immediately in effect guidance Notifying the Center for Devices and Radiological Health of a Permanent Discontinuance or Interruption in Manufacturing of a Device Under Section 506J of the Federal Food, Drug, and Cosmetic Act During the COVID-19 Public Health Emergency.

    This guidance is intended to assist manufacturers in providing FDA timely, informative notifications about changes in the production of certain medical device products that will help the Agency prevent or mitigate shortages of such devices during the COVID-19 public health emergency.

    On May 11, 2020, the FDA will host a webinar for medical device manufacturers and others interested in learning more about the guidance.

  • Diagnostics update to date:
    • During the COVID-19 pandemic, the FDA has worked with more than 385 test developers who have said they will be submitting EUA requests to the FDA for tests that detect the virus.
    • To date, the FDA has issued 60 individual EUAs for test kit manufacturers and laboratories. In addition, 25 authorized tests have been added to the EUA letter of authorization for high complexity molecular-based laboratory developed tests (LDTs).
    • The FDA has been notified that more than 240 laboratories have begun testing under the policies set forth in our COVID-19 Policy for Diagnostic Tests for Coronavirus Disease-2019 during the Public Health Emergency Guidance.
    • The FDA also continues to keep its COVID-19 Diagnostics FAQ up to date.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-daily-roundup-may-6-2020

FDA Approves First Targeted Therapy for Lung Cancer

May 06, 2020: “U.S. Food and Drug Administration approved Tabrecta (capmatinib) for the treatment of adult patients with non-small cell lung cancer (NSCLC) that has spread to other parts of the body.

Tabrecta is the first FDA-approved therapy to treat NSCLC with specific mutations (those that lead to mesenchymal-epithelial transition or MET exon 14 skipping).

The FDA also approved the FoundationOne CDx assay (F1CDx) as a companion diagnostic for Tabrecta.

Most patients had tumour samples that were tested for mutations that lead to MET exon 14 skipping using local tests and confirmed with the F1CDx, which is a next-generation sequencing-based in vitro diagnostic device that is capable of detecting several mutations, including mutations that lead to MET exon 14 skippings.

“Lung cancer is increasingly being divided into multiple subsets of molecularly defined populations with drugs being developed to target these specific groups,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research.

“Tabrecta is the first approval specifically for the treatment of patients with non-small cell lung cancer whose tumors have mutations that lead to MET exon 14 skipping. This patient population now has an option for a targeted therapy, which they didn’t have prior to today.”

NSCLC is a disease in which malignant cancer cells form in the tissues of the lung. It is the most common type of lung cancer with up to 90% of all lung carcinomas falling into the non-small cell category.

NSCLC occurs when healthy cells become abnormal and grow rapidly. One danger of this form of cancer is that there’s a high likelihood that the cancer cells will spread from the lungs to other organs and body parts.

Cancer metastasis consists of a sequential series of events, and MET exon 14 skipping is recognized as a critical event for metastasis of carcinomas.

Mutations leading to MET exon 14 skipping are found in 3-4% of patients with lung cancer.

Tabrecta is a kinase inhibitor, meaning it functions by blocking a key enzyme that results in helping to stop the tumor cells from growing.

The FDA approved Tabrecta based on the results of a clinical trial involving patients with NSCLC with mutations that lead to MET exon 14 skippings, epidermal growth factor receptor (EGFR) wild-type and anaplastic lymphoma kinase (ALK) negative status, and at least one measurable lesion.

During the clinical trial, participants received Tabrecta 400 mg orally twice daily until disease progression or unacceptable toxicity.

The major efficacy outcome measure was overall response rate (ORR), which reflects the percentage of participants that had a certain amount of tumor shrinkage.

An additional efficacy outcome measure was duration of response (DOR). The efficacy population included 28 patients who had never undergone treatment for NSCLC and 69 previously treated patients.

The ORR for the 28 participants was 68%, with 4% having a complete response and 64% having a partial response. The ORR for the 69 participants was 41%, with all having a partial response.

Of the responding participants who had never undergone treatment for NSCLC, 47% had a duration of response lasting 12 months or longer compared to 32.1% of the responding participants who had been previously treated.

Common side effects for patients taking Tabrecta are peripheral edema (leg swelling), nausea, fatigue, vomiting, dyspnea (shortness of breath) and decreased appetite.

Tabrecta may cause serious side effects including interstitial lung disease (a group of lung conditions that causes scarring of lung tissues) or pneumonitis (inflammation of the lung tissue).

Tabrecta should be permanently discontinued in patients with these side effects.

Tabrecta may also cause hepatotoxicity (damage to liver cells), and health care professionals should monitor a patient’s liver function tests prior to starting and when taking Tabrecta. If a patient experiences hepatotoxicity,

Tabrecta should be withheld, dose reduced or permanently discontinued. Based on a clear positive signal for phototoxicity (drug-induced damage to cells that is enhanced by UV light) in laboratory studies in cells, patients may be more sensitive to sunlight and should be advised to take precautions to cover their skin and use sunscreen and not to tan while taking Tabrecta.

Tabrecta may cause harm to a developing fetus or newborn baby.

Health care professionals should advise pregnant women of this risk and should advise both females of reproductive potential and male patients with female partners of reproductive potential to use effective contraception during treatment with Tabrecta and for one week after the last dose.

“In the face of the COVID-19 pandemic, our regular work on reviewing treatments for patients with cancer is moving forward,” said Pazdur.

“The impact may be hardest on those with acute or chronic medical conditions and those with weakened immune systems, such as that caused by cancer and some forms of cancer treatment.

We are working to address critical issues for patients with cancer and their health care providers and continuing to expedite oncology product development in this critical time.”

Tabrecta was approved under the Accelerated Approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally provide a meaningful advantage over existing treatments.

The FDA granted this application Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies, and Priority Review designation.

Tabrecta received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Tabrecta to Novartis Pharmaceuticals Corporation. The approval of the F1CDx companion diagnostic was granted to Foundation Medicine, Inc.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices.

The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.”

https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-treat-aggressive-form-lung-cancer

Medical writing Module 2: Epidemiology and Evidence-Based Medicine

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In module 1 i.e. induction of Medical Writing along with Types and Organisation name and What are skills required etc are covered. Have a look at the given link INTRODUCTION OF MEDICAL WRITING

Now, Let’s start with Module 2 i.e. Epidemiology and Evidence-Based Medicine

“Epidemiology is the analysis of the distribution and determinants in particular populations of health-related conditions or incidents, and the application of this study to the control of the health problems.

Epidemiology is the analysis (scientific, systematic , data-driven) of the distribution (frequency, pattern) and determinants (causes, risk factors) of health-related states and events (not just disease) in different populations (patient is group, individuals collectively viewed) and the application of this study (since epidemiology is a public health discipline) to the management of health problems.

Study

At its foundation, epidemiology is a medical discipline with strong scientific investigation methods.

Epidemiology is data-driven and is based on a clear and objective approach to data collection , analysis and interpretation.

Specific epidemiological methods continue to focus on careful observation and use of relevant reference groups to assess if what has been observed differs from what should be expected, such as the number of cases of disease in a specific area over a given period of time or the degree of exposure among people with the disease.

However, epidemiology also draws on approaches of biological , cultural, social , and behavioral sciences from other scientific fields, including biostatistics and informatics.

Even so, epidemiology is also defined as, and with good reason, the basic physics of public health.

  1. Epidemiology is a quantitative discipline focused on a working knowledge of the opportunities, statistics and sound methods of study.
  2. Epidemiology is a fundamental reasoning method focused on the creation and testing of theories based on scientific fields such as genetics, behavioral sciences, physics and ergonomics with a view to understanding health-related behaviors, states and events.

However, epidemiology is not just a research activity but an essential component of the public health, providing the foundation for directing practical and appropriate public health action based on this science and causal reasoning.

Distribution

Epidemiology is concerned with frequency and pattern of the health events in a population:

Frequency refers not only to the number of health incidents in the population, such as the number of cases of meningitis or diabetes, but also to the relation of this number to population size. The resulting rate allows for epidemiologists to assess the incidence of disease among various populations.

Pattern refers to health related incidents occurring by Time, location, person, etc. Timing trends can be annual, periodic, weekly, hourly, weekday versus weekend, or any other time breakdown that may influence the incidence of disease or injury.

Place patterns include geographic variation, differences between urban and rural, and places of work or school.

Personal characteristics include demographic factors that may be associated with disease risk, injury or disability such as age , sex , marital status, and socio-economic status, as well as behaviors and environmental exposure;

Characterizing health events by time , place and person are descriptive activities of epidemiology, discussed in more detail later in this lesson.

Determinants

Epidemiology is often used to search for the determinants, which are the causes and other factors that affect disease incidence and other events related to health.

Epidemiologists think illness isn’t. Occurrence randomly in a population, but occurs only when an person has the right accumulation of risk factors or determinants.

To search for these determinants, epidemiologists use analytic epidemiology or epidemiologic studies in order to provide the “Why” and “How” of such events.

They assess whether groups with different rates of the disease differ in their demographic characteristics, genetic or immunologic make-up, behaviors, environmental exposures, or other so-called potential risk factors.

if possible, the findings provide sufficient evidence to direct prompt and efficient public health control and prevention measures.

Health-related states or events

Epidemiology was originally focused exclusively on the epidemics of communicable diseases but was subsequently expanded to address endemic communicable diseases and non-communicable infectious diseases.

By the middle of the 20th century, infectious illnesses, accidents, birth defects, maternal-child safety, occupational health, and environmental health had been identified and applied to new epidemiological approaches.

 Then epidemiologists started to look at health and wellness-related habits such as the amount of exercise and the use of seat belt.

Nowadays, with the recent explosion in the molecular methods, epidemiologists can make significant strides in examining genetic markers of disease risk.

Certainly, the term health-related states or events may be seen as anything that affects the well-being of a population.

nevertheless, many epidemiologists still use the term “disease” as shorthand for the wide range of the health-related states and events that are studied.

Specified populations

Although epidemiologists and direct health-care providers (clinicians) are both concerned with occurrence and control of disease, they vary greatly in how they view “the patient.”

The clinician is anxious about the health of an individual; the epidemiologist is anxious about the collective health of the people in a community or population.

Or one can say,  the clinician’s “patient” is the individual; the epidemiologist’s “patient” is the community.

Therefore, the clinician and the epidemiologist have diverse responsibilities when faced with a person with illness.

For example, when the patient with diarrheal disease presents, both are interested in establishing the correct diagnosis.

On the other hand, while the clinician usually focuses on treating and caring for the individual, the epidemiologist focuses on identifying the exposure or source that caused the illness; the number of other persons who may have been similarly exposed; the potential for the further spread in the community; and interventions to prevent additional cases or recurrences.

Application

Epidemiology is not just “the study of” health in the population; it also involves applying the knowledge gained by the studies to the community-based practice.

Like practice of medicine, the practice of epidemiology is both a science and an art. To make the proper diagnosis and prescribe appropriate treatment for the patient, the clinician combines medical (scientific) knowledge with the experience, clinical judgment, and understanding of the patient.

Likewise, the epidemiologist uses the scientific methods of the descriptive and analytic epidemiology as well as experience, epidemiologic judgment, and understanding of the local conditions in “diagnosing” the health of a community and proposing appropriate, practical, and acceptable public health interventions to manage and prevent disease in the community.

Evidence-Based Medicine

Evidence-based medicine (EBM) definition has generated considerable concern among health care professionals over the last decade.

According to definition Evidence-Based Medicine represents the integration of clinical expertise, patient’s values and best available evidence in the process of decision making related to patients health care.

Evidence-based medicine (EBM) is the deliberate, clear, judicious, and fair use of new, best evidence in individual patient care decision making.

EBM combines the best available scientific knowledge with the clinical experience and patient beliefs. It is a trend aimed at increasing the use of high-quality clinical research in making clinical decisions.

EBM needs the clinician’s new skills, including successful literature-searching, and the application of structured standards of evidence in clinical literature evaluation.

Evidence-based medicine practice is a lifelong, self-directed, problem-based learning experience in which caring for one’s own patients provides the need for clinically relevant knowledge about treatment, prognosis, rehabilitation and other clinical and health-care concerns.

It’s not “cookbook” of recipes, but it offers cost-effective and improved health care with its successful implementation. The main distinction between evidence-based medicine and conventional medicine is not that the evidence is taken into account by EBM when the latter does not. Both takes into account evidence; however, EBM demands stronger evidence than commonly used.

One of the greatest accomplishments in evidence-based medicine has been the production in systematic reviews and meta-analyses, methods by which researchers define several studies on a subject, isolate the best ones and then critically examine them to summarize the best evidence available.

Tomorrow’s EBM-oriented clinicians have three tasks: a) to use summaries of evidence in clinical practice; b) to help establish and update selected systematic reviews or evidence-based recommendations in their field of expertise; and c) to enroll patients in the treatment, diagnosis, and prognosis studies on which medical practice is based.

Medical awareness is growing every day, such that commonly established theories easily become old and even an influx of scientific evidence becomes difficult to pursue.

There are apparent challenges as physicians try to keep up with the latest developments reported in medical journals: for example, general practitioners can read 19 papers per day, and we know that many of them only have one hour a week for this.

Need for evidence-based approach in making decisions in the family medicine

The core of Family medicine in relation to doctor-patient.

One of the core aspects of this partnership is the decision-making process, which can differ from specific types of clinical decisions (e.g. the patient has a sore throat, larynx was red but without suppuration-why, it will prescribe antibiotics?) or (patient complained of frontal pain for two weeks, she was present when a patient walked-do you need to conduct CT of the head?), etc.

Difference between evidence- based medicine and evidence based health care

Having a distinction between these two words is worthwhile. Evidence-based medicine is a physician’s systematic approach to decision taking applicable to the actual patient.

Unlike this, Evidence-based health care is a much broader term which requires advanced understanding of the beliefs, values and attitudes of patients, families and physicians.

Evidence-based health care is also based on evidence, but primarily population-level data.

Gap between research and practice

One of the primary reasons why there is a great interest in pursuing evidence-based medicine is the increasing number of cases where traditional medical practice can not keep up with the clinical evidence available.

For example , despite strong evidence during the seventies of the last century that treatment such as thrombolytic therapy and aspirin use was successful in treating acute myocardial infarction, it took nearly a decade for such therapies to become standard in clinical procedures for acute myocardial infarction patients.

Likewise, there are examples of complicated scientific research (evidences) being available everywhere, and its practical application. On the one hand, there is a lack of resolution that will synthesize the primary scientific researches and make systematic results.

On the other side, that indicates lack of ability of available evidences obtained in research which will gain relevant information which consumers of health services and medical professional needs to make decisions. In broader sense, that reflects lack of appropriate frames, systems and strategies which will more efficiently influence of professional conduct.

Complexity of the primary health care (family medicine)

It is understood that the patients come to the family doctor with poorly described symptoms and wide clinical differences-the number of these patients in family practice is definitely the largest.

 They are so called symptoms of illness in the “grey zone”, generally multiple complains of the patients on different organic systems. Rarely that is a single problem.

The truth is that it is only possible to solve a limited number of cases during the first doctor-patient meeting. Family practitioner is also unable to plan patient treatment because it is a case of complicated conditions and it is difficult to schedule treatment.

For general practice, the dynamic nature of research ensures that the patient needs assistance in the dimension of the illness (feeling ill) for which there is no clear proof of any intervention’s efficacy.

Gill and colleagues’ study is based on a longitudinal review of series of doctor-patient interactions, showing that high percentage (81 percent) of general practice intervention can be backed by evidence from randomized controlled trials and (or) compelling non-experimental evidence.

There is also a need to explore how the dynamics of the doctor-patient relationship within family medicine can be integrated.

One of EBM’s key principles is the hierarchy of validating facts based on which judgment is taken, meaning it is important to determine the importance of evidence before making decisions.

According to that concept most important evidence, for example effectiveness of the single therapeutic mean, comes from the results of the multicenter, randomized, comparison, controlled clinical study.
Evidences of least value are based on the studies of the physiology functions and clinicians observations.

Classification of evidence – information levels

Evidence-based medicine categorizes different forms of scientific evidence and rates them out of the numerous inequalities that bedeviled medical science according to the extent of their liberation.

1.Evidences obtained by the meta-analysis of several randomized controlled research (RCR).

1b.Evidences from only one RCR.

2a.Evidences from well designed controlled research RCR.

2b.Evidences from one quasi experimental research.

3.Evidences from the non experimental studies (comparative research, case study), according to some, for example Textbooks.

4.Evidences from experts and clinical practice.

The principle of EBM emphasizes, that the foundation of any medical decisions regarding the optimal diagnostic or therapy procedure are scientific evidences from clinical research, and clinical experience and intuition are of great help, but not main basis in decision-making.

How to start: 5 steps process for use of evidence oriented approach in family medicine

Where do family medicine doctors continue in their daily practice if they want to follow evidence-based approach? The McMaster University Community for Evidence-Based Medicine Resource defined the method that each individual physician will adopt in implementing this approach in 5 phases.

  • Problem definition,
  • Search for wanted sources of the information,
  • Critical evaluation of information,
  • Application of information of the patient,
  • Efficacy evaluation of this application on a patient.
 Step 1. Defining problem

Each doctor several times the day is in the position of making various medical decisions. Often in process of the medical decision-making occur questions such as: for and against the use of certain therapies, whether to use a diagnostic test or screening procedure, the risk or prognosis of the particular disease or cost-effectiveness of specific interventions.

It is clear that the already busy doctor, will not be able to answer in this way all the questions that come in practice and therefore must resort to the process of determining priorities, as well as refining issues that needs to be asked.

A clinician starts his or her search for the best and newest data needed to solve individual patient’s problem by formulating an answerable clinical question. Good clinical question must be clear, directly focused on the problem, and answerable by searching the medical literature.

PICO format

A good clinical question should have four essential components structured in the PICO format (Patient or problem, Intervention, Comparison, Outcome).

PICO format:

  • the patient or problem – who are the relevant patients, what kind of the problem we try to solve?
  • the intervention – what is the management strategy, diagnostic test or exposure (drugs, diagnostic test, foods or surgical procedure)?
  • comparison of interventions – what is the control or alternative management strategy, test or exposure that we will compare?
  • the outcome – what are the patient-relevant consequences of the exposure in which we are interested?

Type of clinical question

The most common type of clinical question is about how to treat a disease or condition. Such questions are questions about intervention.

Types of clinical questions:

  • questions about intervention
  • questions about etiology and risk factors
  • questions about frequency and rate
  • questions about diagnosis
  • questions about prognosis and prediction
  • question about cost-effectiveness
  • question about phenomena
Step 2. Search for wanted sources of information

After formulating the clinical question, which stems from a concrete patient, the next step is to search for relevant evidence that will provide the answer to the question.

This is not always easy, especially in the Family medicine, in which the problems caries the poorlydefined problems in the start.

Moreover, there are several sources of knowledge that may aid, including medical journals, coping with other family medicine concerns, looking for online records, and connecting with colleagues.

The ideal information source is valid (contains high quality data), relevant (clinically applicable), comprehensive (has data on all benefits and harms of all possible interventions), and is user-friendly (is quick and easy to access and use).

Step 3. Critical evaluation of the information

It is important to read it carefully when we decide which magazine to read, since not all of the published information is of equal quality and importance. Critical assessment of the papers is a process requiring thorough reading and review of the methods, contents and conclusions.

A key question that should be kept in mind is “Do I believe in the results enough that I’ll be ready to a similar approach, or in achievement of similar results with my patients?” Skills to obtain the ability of the critical evaluation should be learned and practiced as any other clinical skills.

Step 4. Application of information of the patient

In practice, the fourth step in the process of using Evidence Based Medicine is the decision on how to apply the information acquired on the particular circumstances pertaining to each patient. This is possibly a critical, if not the most complicated, step in the process.

Now it is necessary to decide whether there is something in relation to our patient because of which it would be necessary to discard the acquired information.

The questions that we should ask before the decision to apply the results of the study are:

Are the participants in the study similar enough to my patient?

Is the treatment available and is the health care system prepared to fund it?

What alternatives are available?

Do the potential side effects of the drug or procedure outweigh the benefits?

Are the outcomes appropriate to the patient? Does treatment conflict with the patient’s values and expectations?

When anything does not work, it is important to balance the potential harm from the gain and do all that in cooperation with the individual, where in practice our decision will be shared in the end.

Step 5. Efficacy evaluation of EBM application on a patient

The final step is the evaluation of Evidence – based approach and efficiency of its application to a specific patient. When anything does not work, it is important to balance the potential harm from the gain and do all that in cooperation with the individual, where in practice our decision will be shared in the end.

If the data differ significantly, it would be necessary to investigate why some patients did not respond to the changes introduced in the expected way and what can be done to change it.

The EBM-oriented clinicians of the tomorrow have three tasks:

To use evidence summaries in the clinical practice;

To help develop and update selected systematic reviews or evidence-based guidelines in their area of the expertise; and

To enrol patients in studies of treatment, diagnosis and prognosis on which medical practice is based.

Many epidemiological principles, methods and techniques are put into good use in EBM.

The EB “movement” is attractive in it’s use of clearly defined procedures, generalizing (not always explicitly) the application of good epidemiologic principles, methods, and techniques. Epidemiology now needs to help determine the use of an EB approach.”

https://www.cdc.gov/csels/dsepd/ss1978/lesson1/section1.html
https://en.wikipedia.org/wiki/Epidemiology
https://www.eupati.eu/pharmacoepidemiology/evidence-based-medicine/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3789163/
https://www.hopkinsmedicine.org/gim/research/method/ebm.html

New targeted therapies first line for prostate cancer by ICMR

May 06, 2020: “The Institute of Cancer Research, London, has broadly welcomed the approval of targeted hormone therapies enzalutamide and abiraterone as first-line NHS treatments for men with advanced prostate cancer.

Its experts said newly published interim guidance by NHS England was an example of how modern treatments that can be taken at home could relieve pressure on the NHS during the coronavirus pandemic.

But The Institute of Cancer Research (ICR) was also critical of NHS England for taking so long over its recommendation, and for limiting use of abiraterone only to patients who could not take enzalutamide.

Tablets taken at home

Standard treatment for men when they are first diagnosed with advanced prostate cancer is hormone therapy – either on its own, or together with docetaxel chemotherapy.

Docetaxel is normally given as six three-weekly infusions in hospital and can significantly weaken patients’ immune system and cause inflammation of the lungs – putting men at risk during the current COVID-19 pandemic.

Treatment with enzalutamide or abiraterone can not only prevent patients having to receive docetaxel chemotherapy but is also given as tablets which men can take at home – avoiding unnecessary pressures on the NHS.”

https://www.icr.ac.uk/news-archive/approval-of-targeted-therapies-first-line-for-prostate-cancer-will-ease-covid-19-pressures

NICE publishes rapid COVID-19 guideline for acute kidney injury

May 06, 2020: The National Institute for Health and Care Excellence has published a new COVID-19 rapid guideline on acute kidney injury (AKI).
The purpose of this guideline is to help healthcare professionals prevent, detect and manage acute kidney injury in adults in hospital with known or suspected COVID-19.

This is important to improve outcomes and reduce the need for renal replacement therapy.

This guideline focuses on what you need to stop or start doing during the COVID-19 pandemic. Use it alongside your usual professional guidelines, standards and laws (including equalities, safeguarding, communication and mental capacity).

This guideline is for:

  • health and care practitioners
  • health and care staff involved in planning and delivering services
  • commissioners.

The recommendations bring together:

NICE has developed these recommendations in direct response to the rapidly evolving situation and so could not follow the standard process for guidance development.

The guideline has been developed using the interim process and methods for developing rapid guidelines on COVID-19 and includes a systematic literature search.

The evidence tables for this search will be published alongside the guideline.

The recommendations are based on evidence and expert opinion and have been verified as far as possible. We will review and update the recommendations as to the knowledge base and expert experience develops.

https://www.nice.org.uk/guidance/ng175