CLINSQUARE: CLINICAL RESEARCH COURSES
Friday, February 7, 2025
CLINSQUARE: Clinical Rsearch Courses by LIFEPRONOW
Home Blog Page 19

What Is CDISC and What Are CDISC Data Standards?

admin
-
0
What Is CDISC and What Are CDISC Data Standards?

Introduction

Clinical trials are relatively simple to conduct. We want to know if a new drug is effective and, if so, how effective it is. We will test this medicine on a few thousand people to see how they respond.

We capture their thoughts, examine them for a dozen health indicators, then examine a ton of tables containing collected data before arriving at a conclusion.

All of these procedures are primarily dependent on one thing: data. And how thoroughly it’s documented, gathered, compiled, and analysed. For the most phase, humanity has done a good job working with data. However, as we grow older, our need expand.

Data sharing and accessibility are two of today’s most important aspects of clinical research. We looked at the most common drug data APIs previously. Now we’ll look at the CDISC guidelines and how they affect scientists.

The “Clinical Data Interchange Standards Consortium,” or CDISC, is a global non-profit organisation that actively develops data standards based on the combined knowledge and experience of volunteers in the pharmaceutical industry.

CDISC standards are open source, global, and universal.

The medical community benefits in the following ways.

For researchers, clear and straightforward data management at all stages of clinical research means speedier discoveries and easier sharing and understanding of study results by the community.

For Pharma companies, CDISC standards are required by FDA, PMDA, and EMA, thus the submission and review procedure is simple and quick.

For technology vendors, the ability to design solutions that meet the needs of the research community and employ standardised datasets for machine learning in the pharmaceutical industry.

Overall, standards make it easier to interpret massive amounts of data, ranging from patient questionnaires to information regarding laboratory samples. Let’s go over the different CDISC standards.

CDISC standards fall into four categories: fundamental or Data content standards  (SEND, PRM, CDASH, SDTM, ADaM).

These are the foundation standards for a number of other CDISC standards that assist data collection, management, analysis, and reporting throughout the clinical trial process.

Standards for data exchange (SDM-XML, ODM-XML, Define-XML, CTR-XML). CDISC uses a standard XML for data interchange that is accompanied by industry-specific requirements.

The core requirements for many disease areas are specified in these standards. Here’s an example of a user guide that explains how to collect data and perform COVID-19 trials.

What Does CDISC Do & Why Is CDISC Important?

CDISC develops and disseminates standards for the collecting, exchange, submission, and archiving of data for the development of medical and biopharmaceutical products.

The consortium collaborates with international organisations such as the U. S. FDA, the European Medicines Agency (EMA), Japan’s Pharmaceuticals and Medical Devices Agency (PMDA), and China’s National Medical Products Administration (NMPA) to develop guidelines and requirements that influence clinical and nonclinical data standards.

CDISC standards evolve and change in accordance with worldwide rules. CDISC standards have numerous advantages.

Implementing CDISC data standards has a number of advantages, including:

• CDISC standards promote transparency throughout the medical research process, from protocol development to data and result reporting.

• By speeding regulatory processes during medication development, CDISC standards can reduce timeframes and costs, resulting in a faster marketing authorisation.

• CDISC standards allow FDA reviewers to spend more time on the science of drug development by reducing the amount of time they spend reviewing data.

• When CDISC data standards are implemented, CROs and Sponsors can exchange high-quality, interpretable data quickly and easily.

CDISC Data Standards in Clinical Research & Clinical Studies

CDISC datasets assist in providing clear and standardised clinical trial data to regulatory organisations.

When data is poorly organised or difficult to interpret, it can result in governmental resistance or delays in the drug development process, as effort is spent organising and making sense of the data.

Sponsors can structure their raw data more efficiently using CDISC data standards, which are universally recognised and essential for successful data submissions.

Implementing Controlled Terminology is another technique to create clarity (CT). CT is an evolving dictionary of recognised terms that are used to standardise data collected across studies into a single value for computerised data processing and submission.

CT offers data a clear context and eliminates uncertainty in result evaluation.

Pharmacokinetic CDISC Data Standards

Pharmacokinetic (PK) data is an essential subset of clinical trial data inside CDISC. CDISC data management with PK data is a very specialised area.

Understanding the distinctions between the sources and types of PK data acquired during a trial, as well as how to merge those different data sources in the correct format to create a dataset suitable for PK studies, is crucial.

PK and CDISC collaborate to produce a simple and easy-to-understand clinical trial submission package.

CDISC has three key data standards:

SEND for nonclinical data, SDTM for clinical data, and ADaM for analysis ready data, as previously mentioned.

Clinical and bioanalytical data must be reconciled in the PK domains for SDTM and ADaM. Specialized domains are established to highlight the link between bioanalytical data and estimated PK parameters.

CDISC Domains

Domains are used to organise SEND, SDTM, and ADaM data. A domain is a collection of linked observations on a specific topic collected for all human or animal subjects in a clinical or nonclinical study.

Clinical PK Domain Definitions:

Pharmacokinetic concentrations (PC) domain, pharmacokinetic parameters (PP) domain, and related records (RELREC) domain are all relevant PK domains for SEND and SDTM.

The analysis dataset of pharmacokinetic concentrations (ADPC) and the analysis dataset of pharmacokinetic parameters (ADPP), which are used for PK analyses, are the key PK domains for ADaM.

PC: Data obtained for analytes (typically study medications and/or their metabolites) in tissue (e.g., serum or plasma) and fluid concentrations as a function of time before and after dosing the research drug.

PP: PC data in a standardised format describing the PK parameters of the time-concentration curve (e.g., area under the curve, maximum concentration, time of maximum observed concentration sampled during a dosing interval).

RELREC: Data that relates the specific PK concentrations in the PC dataset to the PP dataset’s corresponding PK parameters.

ADPC: Analyze ready data collected for analyte concentrations in tissue and fluid as a function of time. This dataset may contain information not found in the SDTM PC domain, such as elapsed time calculations, analysis flagging, and imputations of values below the quantification lower limit.

ADPP: Analysis ready data for PC data that describes the characteristics of the time-concentration curve. This dataset may include flags for values to be utilised in further analysis, such as tables, listings, figures, or bioequivalence/bioavailability assessments, in addition to the SDTM PP dataset.

Nonclinical PK Domain Definitions:

The pool definitions (POOLDEF) and supplemental qualifiers for pharmacokinetic concentration (SUPPPC), as well as the PC and PP domains outlined above under the clinical PK domains, are all important domains for SEND.

POOLDEF: Data utilised in a pooled profile for analysis to combine and identify individual animals.

SUPPPC: Supplementary dataset that contains extra qualifiers not captured by PC variables.

SEND:SEND stands for “Standard for Nonclinical Data Exchange.” All nonclinical data is organised, structured, and formatted according to SEND.

Based on the format and metadata provided by the SDTM, the SEND Implementation Guide (SEND-IG) includes predefined areas and samples of nonclinical (animal) data.

Single-dose toxicity, repeat dosage toxicology, and carcinogenicity studies are all supported by the current SEND-IG version 3.1.1.

SEND also covers respiratory and cardiovascular testing in safety pharmacology investigations. Data collection for immunogenicity specimen assessment is currently in the works.

SDTM: “Study Data Tabulation Model” is what SDTM stands for. SDTM is the most extensively used CDISC standard. SDTM establishes a common standard for constructing and structuring data sets for particular clinical studies.

The SDTM Implementation Guide (SDTM-IG) provides a standardised, pre-defined collection of domains for clinical data input, each based on the SDTM’s structure and metadata.

SDTM data is unprocessed data that frequently requires additional manipulation before it is ready for analysis.

ADaM: “Analysis Data Model” is what ADaM stands for. ADaM can alternatively be thought of as “analysis ready” data. The way data is displayed is the key distinction between ADaM and SDTM standards.

SDTM is a standard for collecting and mapping data from raw sources, whereas ADaM is a standard for creating analysis-ready data, which frequently uses SDTM data as a source. The FDA can readily repeat analyses using ADaM databases.

Who Belongs to CDISC and Why?

CDISC’s membership covers a diverse spectrum of clinical research organisations, including:

  • Clinical research organizations
  • Government agencies
  • Technology service providers
  • Biotech firms
  • Academic institutions
  • Pharmaceutical companies
  • Non-profit organizations
  • Healthcare providers

These individuals are all motivated by the desire to maximise the effect of clinical research results.

CDISC data standards aid understanding and interpretation of clinical data.

Being a member of CDISC has a number of advantages, including access to a variety of tools, workshops, and training courses designed to help clinical researchers better understand and execute CDISC’s data management standards.

BMS Provides Update on Evaluating Opdivo Plus Yervoy for Urothelial Carcinoma

admin
-
0
BMS Provides Update on Evaluating Opdivo Plus Yervoy for Urothelial Carcinoma

May 16, 2022: “Bristol Myers Squibb announced the Phase 3 CheckMate -901 trial, comparing Opdivo (nivolumab) plus Yervoy (ipilimumab) to standard-of-care chemotherapy as a first-line treatment for patients with untreated unresectable or metastatic urothelial carcinoma, did not meet the primary endpoint of overall survival (OS) in patients whose tumor cells express PD-L1 ≥1% at final analysis.

The company remains blinded to the data, and an independent Data Monitoring Committee recommended that the trial continue to assess other primary and secondary endpoints.

No new safety signals were observed at the time of the analysis.

“Despite some progress in recent years, metastatic urothelial carcinoma remains a difficult disease to address, with a limited number of treatment options that can extend patients’ lives,” said Dana Walker, M.D., M.S.C.E., vice president, development program lead, genitourinary cancers, Bristol Myers Squibb.

“Opdivo plus Yervoy has demonstrated durable, long-term survival improvements in several challenging-to-treat advanced cancers, and we are disappointed that the final analysis of CheckMate -901 did not show this same benefit in urothelial carcinoma patients whose tumor cells express PD-L1 ≥1%.

We remain committed to advancing research in urothelial carcinoma, we look forward to seeing data from other parts of the CheckMate -901 trial, and we thank all of the patients, investigators and site personnel involved.”

The CheckMate -901 trial is also assessing Opdivo plus Yervoy in patients with unresectable or metastatic urothelial carcinoma who are ineligible for cisplatin-based chemotherapy.

Additionally, a sub-study of CheckMate -901 with pivotal intent is evaluating Opdivo in combination with chemotherapy versus chemotherapy alone in patients who are eligible for cisplatin-based chemotherapy.

The CheckMate -901 primary study and sub-study are ongoing, and the company will report results for these additional components of the study when available.

Opdivo plus Yervoy-based combinations have shown significant improvements in OS in six Phase 3 clinical trials in five tumors to date: non-small cell lung cancer, metastatic melanoma, advanced renal cell carcinoma, malignant pleural mesothelioma and esophageal squamous cell carcinoma.

In addition, Opdivo has shown clinical benefit in second-line metastatic urothelial carcinoma and adjuvant muscle-invasive urothelial carcinoma.

About CheckMate -901

CheckMate -901 is a Phase 3, randomized, open-label trial evaluating Opdivo in combination with Yervoy (primary study)or Opdivo in combination with chemotherapy (sub-study) compared to standard-of-care chemotherapy alone, in patients with untreated unresectable or metastatic urothelial cancer.

In the primary study, a total of 707 patients were randomized to receive either Opdivo (1 mg/kg) plus Yervoy (3 mg/kg) every three weeks for four cycles, followed by Opdivo (480 mg) every four weeks for a maximum of two years, or chemotherapy (gemcitabine-cisplatin or gemcitabine-carboplatin) every three weeks for six cycles.

The primary endpoints of the primary study are overall survival (OS) in patients who are ineligible for cisplatin-based chemotherapy and OS in patients with tumor cell PD-L1 expression ≥1%.

Key secondary endpoints include OS in all randomized patients, progression-free survival (PFS) and safety outcomes.

A sub-study of CheckMate -901 is evaluating Opdivo in combination with chemotherapy versus chemotherapy alone in patients who are eligible for cisplatin-based chemotherapy.

The OS outcomes for patients whose tumor cells express PD-L1 ≥1% are based on the final efficacy analysis for this endpoint of the CheckMate -901 primary study; the other parts of the study are ongoing.

About Urothelial Carcinoma

Bladder cancer is the 10th most common cancer in the world, with more than 573,000 new cases diagnosed annually. Urothelial carcinoma, which most frequently begins in the cells that line the inside of the bladder, accounts for approximately 90% of bladder cancer cases.

In addition to the bladder, urothelial carcinoma can occur in other parts of the urinary tract, including the ureters and renal pelvis.

The majority of urothelial carcinomas are diagnosed at an early stage, but rates of recurrence and disease progression are high.

Approximately 50% of patients who undergo surgery will experience disease recurrence. Additionally, approximately 20% to 25% of patients with urothelial carcinoma develop metastatic disease.

For patients with metastatic cancer, the prognosis is poor, with a median overall survival of approximately 12 to 14 months when treated with systemic therapy.

The poor durability of responses in the first-line setting presents a major challenge in the treatment of metastatic disease, and there are limited treatment options in the second-line setting for patients with advanced urothelial carcinoma.”

https://news.bms.com/news/corporate-financial/2022/Bristol-Myers-Squibb-Provides-Update-on-CheckMate–901-Trial-Evaluating-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-as-First-Line-Treatment-for-Patients-with-Unresectable-or-Metastatic-Urothelial-Carcinoma/default.aspx

Sanofi’s Sarclisa combination shows positive results in the multiple myeloma patients

admin
-
0
Sanofi’s Sarclisa combination shows positive results in the multiple myeloma patients

May 15, 2022: “Latest results from the Phase 3 IKEMA clinical trial evaluating Sarclisa® (isatuximab) in combination with carfilzomib and dexamethasone (Kd) demonstrated a median progression free survival (mPFS) of 35.7 months (Hazard Ratio HR 0.58; 95% Confidence Interval CI: 25.8 to 44.0; n=179), compared to 19.2 months in patients treated with Kd alone (95% CI: 15.8 to 25.1; n=123), as evaluated by an Independent Review Committee.

These results, presented at the Controversies in Multiple Myeloma World Congress, represent the longest mPFS among studies investigating a proteasome inhibitor backbone in the second-line setting for the treatment of relapsed multiple myeloma (MM).

These data will also be presented at the European Society for Medical Oncology on May 19.

Philippe Moreau, MD
Head of the Department of Hematology, University Hospital of Nantes, France
“The increase in progression free survival, observed consistently across all subgroups, when adding Sarclisa to carfilzomib and dexamethasone is remarkable in patients with relapsed multiple myeloma in a proteasome inhibitor combination. 

Relapse is common in multiple myeloma, creating the need for differentiated second-line treatments that provide patients a longer period of time without disease progression.

This updated analysis reinforces the potential for Sarclisa to become a new standard of care for patients with relapsed multiple myeloma.”

A PFS analysis following the U.S. Food and Drug Administration recommendations on censoring rules, as applied in the approved U.S. prescribing information, showed an mPFS of 41.7 months for Sarclisa added to Kd (Sarclisa combination therapy) compared to 20.8 months in patients treated with Kd alone (HR 0.59; 95% CI: 27.1 to Not Calculable NC).

Time to next treatment for patients treated with Sarclisa combination therapy was 44.9 months (HR 0.55; 95% CI: 31.6 to NC) versus those treated with Kd alone at 25 months (95% CI: 17.9 to 31.3).

Time to next treatment measured the interval from the date of randomization to the date of commencement of the next line of therapy, thereby allowing for measurement of the period of therapeutic benefit.

Peter C. Adamson, MD
Global Head of Oncology Clinical Development and Pediatric Innovation at Sanofi
“To observe progression free survival of more than three years in patients with relapsed multiple myeloma when Sarclisa was added to a proteasome inhibitor backbone of therapy is unprecedented and reinforces our confidence in Sarclisa as a potential best in class anti-CD38 antibody.”

The safety and tolerability of Sarclisa observed in this analysis were consistent with the safety profile of Sarclisa in other clinical trials, with no new safety signals observed.

For the Sarclisa combination therapy and Kd groups, the most common adverse events were infusion related reaction (45.8%, 3.3%), diarrhea (39.5%, 32%), hypertension (37.9%, 35.2%), upper respiratory tract infection (37.3%, 27%), fatigue (31.6%, 20.5%), dyspnoea (30.5%, 22.1%), pneumonia (27.1%, 21.3%), back pain (25.4%, 21.3%), insomnia (25.4%, 24.6%), and bronchitis (24.3%, 12.3%).

Treatment exposure in the Sarclisa combination therapy arm was 30 weeks longer than in the control arm.

Treatment emergent adverse events (TEAEs) of ≥ Grade 3 were reported in 83.6% of patients treated with Sarclisa combination therapy and in 73% of those treated with Kd alone.

Serious TEAEs were higher in the Sarclisa combination therapy arm versus Kd alone (70.1% versus 59.8%). No difference was observed after exposure adjustment.”

https://www.sanofi.com/en/media-room/press-releases/2022/2022-05-15-09-30-00-2443369

FDA Encourages Importation of Safe Infant Formula and Other Flexibilities to Further Increase Availability

admin
-
0
FDA Encourages Importation of Safe Infant Formula and Other Flexibilities to Further Increase Availability

May 16, 2022: “The U.S. FDA is announcing a guidance that outlines increased flexibilities regarding importation of certain infant formula products to further increase the availability of infant formula across the country while protecting the health of infants.

The agency is encouraging infant formula manufacturers worldwide to take advantage of these flexibilities.

“The FDA is leaving no stone unturned to further increase the availability of infant formula.

We are doing everything in our power as part of the all-of-government efforts to ensure there’s adequate product available wherever and whenever parents and caregivers need it,” said FDA Commissioner Robert M. Califf, M.D.

“Today’s action paves the way for companies who don’t normally distribute their infant formula products in the U.S. to do so efficiently and safely.

We are hopeful this call to the global market will be answered and that international businesses will rise to the occasion to assist in bolstering the supply of products that serve as the sole source of nutrition for many infants.

With these flexibilities in place, we anticipate that those products that can quickly meet safety and nutrition standards could hit U.S. stores in a matter of weeks.”

The U.S. normally produces 98% of the infant formula it consumes, with the primary source of imports coming from trading partners in Mexico, Ireland and the Netherlands.

However, given the production and distribution issues that have led to reduced supplies of infant formula in some parts of the country, the FDA has outlined a process by which the agency would not object to the importation of certain infant formula products intended for a foreign market or distribution in the U.S. of products manufactured here for export to foreign countries.

It also may provide flexibilities to those who manufacturer infant formula products domestically for export and may be able to increase further domestically produced product for the U.S. market. 

Companies seeking to take advantage of these flexibilities should submit information for the FDA to quickly evaluate whether the product can be used safely and whether it provides adequate nutrition.

For example, labeling, information on nutritional adequacy and safety testing, and information about facility inspection history.

The agency intends to prioritize submissions for products that can demonstrate the safety and nutritional adequacy and have the largest volume of product available and/or those who can get product onto U.S. shelves the quickest.

The FDA is already in discussions with some manufacturers and suppliers regarding additional supply. 

As part of a number of significant actions the FDA has undertaken since February to increase supply, the agency had already implemented a streamlined process to facilitate the importation of infant formula at U.S. ports of entry so that formula coming from abroad can be dispersed quickly throughout the country.

This work has already resulted in more infant formula coming into the U.S. Imports of infant formula year-to-date are up more than 300% from last year.

The FDA has and will continue to actively work with the U.S. Department of Agriculture, U.K., and European authorities to expedite entry for products made abroad. 

All of this around-the-clock work has already begun to improve supply and availability with most manufacturers, now producing at normal or expanded capacity.

The FDA expects that the measures and steps it is taking with infant formula manufacturers and others will mean more and more supply is on the way or on store shelves moving forward. 

Data from Information Resources Inc. (IRI) indicate that in-stock rates in retail stores are improving and the FDA’s actions are expected to continue to increase product availability.

While some data suppliers have reported lower in-stock rates, the most complete data sets available from IRI are showing nearly 80% in-stock rates at the week ending May 8.

The agency’s best current assessment is that with all of the current actions, including today’s announcement, and the potential for Abbott Nutrition’s Sturgis, Michigan, facility to safely resume production in the near-term, the supply of infant formula will continue to improve over the next couple of months.

In the meantime, the agency is encouraged to see that as of early May the amount of infant formula sold in the U.S. continues to rise. 

It is important to understand that only facilities experienced in and already making essentially complete nutrition products are in the position to produce infant formula products that would not pose significant health risks to consumers.

The agency continues to advise against making infant formulas at home.

Caregivers are encouraged to work with their child’s health care provider for recommendations on changing feeding practices, if needed.

The U.S. Department of Health and Human Services has also released a fact sheet with information to help families find infant formula.

The FDA will continue to dedicate all available resources to help ensure that infant formula products remain available for use in the U.S. and will keep the public informed of progress updates.”

https://www.fda.gov/news-events/press-announcements/fda-encourages-importation-safe-infant-formula-and-other-flexibilities-further-increase-availability

FDA Authorizes First COVID-19 Test Available without a Prescription That Also Detects Flu and RSV

admin
-
0
FDA Authorizes First COVID-19 Test Available without a Prescription That Also Detects Flu and RSV

May 16, 2022: “The U.S. FDA authorized the Labcorp Seasonal Respiratory Virus RT-PCR DTC Test for use without a prescription by individuals with symptoms of respiratory viral infection consistent with COVID-19.

This product is the first direct-to-consumer (non-prescription) multi-analyte COVID-19 test authorized by FDA and allows an individual to self-collect a nasal swab sample at home and then send that sample to Labcorp for testing.

The test can identify and differentiate multiple respiratory viruses at the same time, detecting influenza A and B, commonly known as the flu, respiratory syncytial virus, commonly known as RSV, along with SARS-CoV-2, the virus that causes COVID-19.

Results are delivered through an online portal, with follow-up from a health care provider for positive or invalid test results.

“While the FDA has now authorized many COVID-19 tests without a prescription, this is the first test authorized for flu and RSV, along with COVID-19, where an individual can self-identify their need for a test, order it, collect their sample and send it to the lab for testing, without consulting a health care professional,” said Jeff Shuren, M.D., J.D., director of FDA’s Center for Devices and Radiological Health.

“The rapid advances being made in consumer access to diagnostic tests, including the ability to collect your sample at home for flu and RSV without a prescription, brings us one step closer to tests for these viruses that could be performed entirely at home.”

This home sample collection kit can be purchased online or in a store without a prescription.

The samples can be self-collected by individuals ages 18 years and older, self-collected by individuals 14 years and older with adult supervision, or collected with adult assistance for individuals 2 years and older.

This will enable consumers to more easily determine whether they may be infected with COVID-19, flu, or RSV, which can aid in determining if self-isolation (quarantine) is appropriate and to assist with health care decisions after discussion with a health care professional.”

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-first-covid-19-test-available-without-prescription-also

First time an albuterol/budesonide fixed-dose combination rescue medication has been shown to reduce severe exacerbations

admin
-
0
First time an albuterol/budesonide fixed-dose combination rescue medication has been shown to reduce severe exacerbations

May 15, 2022: “Full results from the positive MANDALA Phase III trial showed that PT027 (albuterol/budesonide) at two different strengths of budesonide, an inhaled corticosteroid (ICS), used as an as-needed rescue medicine, demonstrated a statistically significant reduction in the risk of a severe exacerbation versus albuterol rescue in patients with moderate to severe asthma.

PT027 is a potential first-in-class inhaled, fixed-dose combination rescue medication containing albuterol, a short-acting beta2-agonist (SABA), and budesonide in the US. It is being developed by AstraZeneca and Avillion.

Globally, more than 176 million asthma attacks are experienced each year.

Compared with albuterol rescue, PT027 at the 180mcg albuterol/160mcg budesonide dose reduced the risk of a severe exacerbation by 27% (p<0.001) in adults and adolescents.

In the trial, patients were randomised to receive PT027 or albuterol rescue, on top of their usually prescribed maintenance ICS, with or without additional controller medicines.

In secondary endpoints, PT027 (180mcg albuterol/160mcg budesonide) demonstrated a 33% reduction in mean annualised total systemic corticosteroid exposure (p=0.002) and a 24% reduction in annualised severe exacerbation rate (p=0.008).

A numerically higher odds of patients experiencing an improvement in symptom control and quality of life was also observed after 24 weeks of treatment with PT027 compared to albuterol rescue.

Adverse events (AEs) were similar across the treatment groups in the trial and consistent with the known safety profiles of the individual components, with the most common AEs including nasopharyngitis and headache.

Bradley E. Chipps, Past President of the American College of Allergy, Asthma & Immunology and Medical Director of Capital Allergy & Respiratory Disease Center in Sacramento, US, said:

“The MANDALA Phase III trial results demonstrated that PT027, a novel fixed-dose combination of albuterol/budesonide used as-needed, provided additional anti-inflammatory treatment in response to patient symptoms, which led to a reduced risk of severe exacerbations compared with albuterol alone.

These data further strengthen the growing body of evidence around the value of as-needed anti-inflammatory treatment in asthma and support PT027’s potential to transform the current rescue treatment approach.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Asthma is an inflammatory, variable disease and patients are at risk of experiencing a severe exacerbation regardless of disease severity and adherence to treatment.

The results from these Phase III trials support the clinical benefit of PT027, an albuterol/budesonide rescue inhaler, which has the potential to be a first-in-class treatment approach that can prevent asthma attacks over and above their current maintenance therapies.”

In the MANDALA trial, PT027 at a lower budesonide dose (180mcg albuterol/80mcg budesonide), also demonstrated a statistically significant reduction of 17% in the risk of severe exacerbation versus albuterol rescue (p=0.041), when used as an as-needed rescue medicine in adults, adolescents, and children aged 4–11 years.

The results were published in the New England Journal of Medicine and will be presented at the American Thoracic Society (ATS) 2022 International Conference.1,2,4

Also being presented at the ATS International Conference this week are the positive DENALI Phase III trial results.

In this trial, PT027 demonstrated a statistically significant improvement in lung function measured by forced expiratory volume in one second (FEV1), compared to the individual components albuterol and budesonide, and compared to placebo in patients with mild to moderate asthma aged 12 years or older.

Onset of action and duration of effect were similar for PT027 and albuterol. The safety and tolerability of PT027 in DENALI was consistent with the known profiles of the components.”

https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2022/pt027-significantly-reduced-the-risk-of-a-severe-exacerbation-compared-to-albuterol-in-patients-with-asthma.html

FDA Approves Novel, Dual-Targeted Treatment for Type 2 Diabetes

admin
-
0
FDA Approves Novel, Dual-Targeted Treatment for Type 2 Diabetes

May 13, 2022: “The U.S. FDA approved Mounjaro (tirzepatide) injection to improve blood sugar control in adults with type 2 diabetes, as an addition to diet and exercise. Mounjaro was effective at improving blood sugar and was more effective than the other diabetes therapies with which it was compared in clinical studies.   

“Given the challenges many patients experience in achieving their target blood sugar goals, today’s approval of Mounjaro is an important advance in the treatment of type 2 diabetes,” said Patrick Archdeacon, M.D., associate director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research.

Type 2 diabetes, the most common form of diabetes, is a chronic and progressive condition in which the body does not make or use insulin normally, leading to high levels of glucose (sugar) in the blood.

More than 30 million Americans have type 2 diabetes. Despite the availability of many medications to treat diabetes, many patients do not achieve the recommended blood sugar goals.

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are hormones involved in blood sugar control. Mounjaro is a first-in-class medicine that activates both the GLP-1 and GIP receptors, which leads to improved blood sugar control.

Mounjaro is administered by injection under the skin once weekly, with the dose adjusted as tolerated to meet blood sugar goals. 

Three different doses of Mounjaro (5 milligrams, 10 milligrams and 15 milligrams) were evaluated in five clinical trials as either a stand-alone therapy or as an add-on to other diabetes medicines.

The efficacy of Mounjaro was compared to placebo, a GLP-1 receptor agonist (semaglutide) and two long-acting insulin analogs.

On average, patients randomized to receive the maximum recommended dose of Mounjaro (15 milligrams) had lowering of their hemoglobin A1c (HbA1c) level (a measure of blood sugar control) by 1.6% more than placebo when used as stand-alone therapy, and 1.5% more than placebo when used in combination with a long-acting insulin.

In trials comparing Mounjaro to other diabetes medications, patients who received the maximum recommended dose of Mounjaro had lowering of their HbA1c by 0.5% more than semaglutide, 0.9% more than insulin degludec and 1.0% more than insulin glargine. 

Obesity was common among study participants, with an average body mass index of 32 to 34 kilograms/height in meters squared reported at the time of enrollment.

Among patients randomized to the maximum recommended dose, the average weight loss with Mounjaro was 15 pounds more than placebo when neither were used with insulin and 23 pounds more than placebo when both were used with insulin.

The average weight loss with the maximum recommended dose of Mounjaro was 12 pounds more than semaglutide, 29 pounds more than insulin degludec and 27 pounds more than insulin glargine.

Those patients receiving insulin without Mounjaro tended to gain weight during the study. 

Mounjaro can cause nausea, vomiting, diarrhea, decreased appetite, constipation, upper abdominal discomfort and abdominal pain. 

Mounjaro causes thyroid C-cell tumors in rats.

It is unknown whether Mounjaro causes such tumors, including medullary thyroid cancer, in humans. Mounjaro should not be used in patients with a personal or family history of medullary thyroid cancer or in patients with Multiple Endocrine Neoplasia syndrome type 2. 

Mounjaro has not been studied in patients with a history of pancreas inflammation (pancreatitis), and it is not indicated for use in patients with type 1 diabetes. 

Mounjaro received priority review designation for this indication.

A priority review designation directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions. 

The FDA granted the approval of Mounjaro to Eli Lilly and Co.”

https://www.fda.gov/news-events/press-announcements/fda-approves-novel-dual-targeted-treatment-type-2-diabetes

Novo Nordisk and Flagship Pioneering collaborates to create a portfolio of transformational medicines

admin
-
0
Novo Nordisk and Flagship Pioneering collaborates to create a portfolio of transformational medicines

May 10, 2022: “Flagship Pioneering and Novo Nordisk A/S announced a collaboration to create a portfolio of novel research programmes to develop transformational medicines.

The companies will explore opportunities to apply Flagship’s innovative bioplatforms – an ecosystem that currently comprises 41 companies – to scientific challenges in disease areas within cardiometabolic and rare diseases and initiate research programmes based on these.

This is a novel approach to collaboration, between companies providing extensive access to innovation, leveraging the technology platforms of multiple biotech companies to create a portfolio of medicines across several disease areas.

“We are excited about this new agreement which will give Novo Nordisk access to Flagships’ large and diverse portfolio of companies, representing a wide variety of novel cutting-edge technologies and therapeutic modalities,” said Marcus Schindler, PhD, professor, executive vice president and chief scientific officer of Novo Nordisk.

“This is a new and innovative way of collaborating, which combines the strength of Flagship Pioneering’s bioplatforms with Novo Nordisk’s cardiometabolic and rare disease expertise.”

Novo Nordisk will provide funding for initiated research programmes and have an exclusive option to license each program.

The ambition is to initiate three to five research programs within the first three years of the collaboration.

“We enter into this collaboration with Novo Nordisk with a shared vision of creating transformational medicines in disease areas where there continue to be significant needs,” said Paul Biondi, president, Pioneering Medicines and executive partner, Flagship Pioneering.

“This strategic partnership demonstrates the unique advantages of our Pioneering Medicines model in which we bring together complementary capabilities and expertise from multiple companies to deliver life-changing medicines to patients.”

Through the collaboration, Flagship’s Pioneering Medicines and the Novo Nordisk Bio Innovation Hub will jointly select the most promising product concepts and conduct research programmes.

Pioneering Medicines is a strategic initiative within Flagship Pioneering that is dedicated to conceiving and developing a broad portfolio of life-changing treatments by leveraging and expanding the use of Flagship’s innovations.

The Novo Nordisk Bio Innovation Hub is a cross-functional R&D team within Novo Nordisk based in Cambridge, Massachusetts, with an ambition to establish and drive an externally anchored portfolio of co-created breakthrough therapeutic concepts and technologies and delivery projects.

The Bio Innovation Hub, together with the recently acquired Dicerna Pharmaceuticals Inc. in Lexington, Massachusetts, are two of four transformational research units (TRUs) in the Novo Nordisk R&D organisation.”

https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=114563

WHO launches new Nursing and Midwifery Community of Practice for International Nurses Day

admin
-
0
WHO launches new Nursing and Midwifery Community of Practice for International Nurses Day

 May 12, 2022: “On International Nurses Day, 12th May, we celebrate Nurses from all over the world and the important work that they do to save lives and to keep their communities safe.

Today the WHO Chief Nursing Office is officially launching a Nursing and Midwifery Global Community of Practice https://nursingandmidwiferyglobal.org  – a network for nurses, midwives and stakeholders to connect, communicate and collaborate.

We are encouraging everyone to become a member of this growing network to share and learn from one another and from experts in the their specialty areas.

https://www.who.int/news/item/12-05-2022-who-launches-new-nursing-and-midwifery-community-of-practice-for-international-nurses-day

Novartis receives EC approval for Jakavi® for acute and chronic graft-versus-host disease

admin
-
0
Novartis receives EC approval for Jakavi® for acute and chronic graft-versus-host disease

May 5, 2022: “Novartis announced the European Commission has approved Jakavi (ruxolitinib) for the treatment of patients aged 12 years and older with acute or chronic GvHD who have inadequate response to corticosteroids or other systemic therapies.

“Today, 30-60% of patients with GvHD do not respond to first-line steroid treatment, underscoring the need for new approaches to ensure long-term treatment goals are met,” said Dr. Robert Zeiser, University Hospital Freiburg, Department of Haematology, Oncology and Stem Cell Transplantation, Freiburg, Germany.

“The approval of Jakavi offers healthcare providers and patients with GvHD who remain dependent on or refractory to steroids a new way to manage this debilitating and life-threatening condition.”

The approval of Jakavi follows the positive opinion granted in March by the Committee for Medicinal Products for Human Use of the European Medicines Agency, based on the Phase III REACH2 and REACH3 trials in which Jakavi demonstrated superiority in overall response rate (ORR) compared to best available therapy (BAT). \

Results of REACH2 showed 62% ORR with Jakavi at Day 28, compared to 39% for BAT; and REACH3 demonstrated a significantly improved ORR at week 24 (50% vs. 26%) with a higher best ORR (76% vs. 60%) vs. BAT, among steroid-refractory/dependent chronic GvHD patients.

“Five out of ten patients who receive allogeneic stem cell transplants experience the serious and sometimes fatal symptoms of graft-versus-host disease,” says Marie-France Tschudin, Novartis President of Innovative Medicines International and Chief Commercial Officer.

“Jakavi, with this new indication in GvHD, will help to redefine treatment for patients who do not respond to first-line care.”

GvHD occurs when donor cells see the recipient’s healthy cells as foreign and attack them. Symptoms of GvHD can appear in the skin, gastrointestinal tract, liver, mouth, eyes, genitals, lungs and joints.

Approximately 50% of allogeneic stem cell transplant recipients will develop either acute or chronic GvHD.

Both acute and chronic GvHD can be fatal and until now both have lacked an established standard of care for patients who do not adequately respond to first-line steroid treatment.

Currently, there are no other approved therapies for the treatment of GvHD after steroid failures.

About Jakavi® (ruxolitinib)
Jakavi® (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases.

Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease- related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF, and also for patients aged 12 years and older with acute or chronic GvHD who have inadequate response to corticosteroids or other systemic therapies.

Jakavi is approved in over 100 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 85 countries for patients with PV, including EU countries, Switzerland, Japan and Canada.

The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.

Novartis licensed ruxolitinib from Incyte for development and commercialization outside the United States.

Ruxolitinib is marketed in the United States by Incyte as Jakafi® for adults with PV who have had an inadequate response to or are intolerant of hydroxyurea, for adults with intermediate or high-risk MF, for adult and pediatric patients 12 years and older with steroid-refractory acute GvHD, and adult and pediatric patients 12 years and older with chronic GvHD after failure of one or two lines of corticosteroids or other systemic therapy.

Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte.

The safety and efficacy profile of Jakavi has not yet been established outside of its approved indications.”

https://www.novartis.com/news/media-releases/novartis-receives-european-commission-approval-jakavi-be-first-post-steroid-treatment-acute-and-chronic-graft-versus-host-disease

Novartis provides update on production of radioligand therapy medicines

admin
-
0
Novartis provides update on production of radioligand therapy medicines

May 5, 2022 — “Novartis announced a temporary, voluntary suspension of production at its radioligand therapy production sites in Ivrea, Italy and Millburn, New Jersey.

The company has taken this action out of an abundance of caution as it addresses potential quality issues identified in its manufacturing processes.

Novartis is conducting a thorough review of the situation and currently expects to resolve the issues and resume some supply in the next six weeks.

As a result, the company is temporarily suspending delivery of Lutathera® (USAN: lutetium Lu 177 dotatate; INN: lutetium (177Lu) oxodotreotide) in the US and Canada, and 177Lu-PSMA-617 (INN: lutetium (177Lu) vipivotide tetraxetan), marketed as Pluvicto™ (lutetium Lu 177 vipivotide tetraxetan) in the US.

Some doses of Lutathera® (lutetium (177Lu) oxodotreotide) will be available in Europe and Asia from Novartis radioligand therapy production site in Zaragoza, Spain, although there may be some delays in supply.

In addition, Novartis is putting a temporary hold on screening and enrollment for 177Lu-PSMA-617 clinical trials globally, and Lutathera clinical trials in the US and Canada.

Quality and patient safety are our top priorities.

There is currently no indication of any risk to patients from doses previously produced at these sites.

Novartis has notified treatment sites to closely monitor patients who have recently been injected and asked them to report any adverse events to Novartis patient safety.

We recognize that this situation affects patients, their families and care teams. Novartis takes this very seriously and the company is doing everything it can to resolve this issue and resume patient doses as quickly as possible.

Health authorities have been informed and will receive additional updates as they are available.”

https://www.novartis.com/news/media-releases/novartis-provides-update-production-radioligand-therapy-medicines

Pfizer to Acquire Biohaven Pharmaceuticals

admin
-
0
Pfizer to Acquire Biohaven Pharmaceuticals

May 10, 2022: ” Pfizer Inc.and Biohaven Pharmaceutical Holding Company Ltd. announced that the companies have entered into a definitive agreement under which Pfizer will acquire Biohaven, the maker of NURTEC® ODT, an innovative dual-acting migraine therapy approved for both acute treatment and episodic prevention of migraine in adults.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20220510005676/en/

Under the terms of the agreement, Pfizer will acquire all outstanding shares of Biohaven not already owned by Pfizer for $148.50 per share in cash.

Biohaven common shareholders, including Pfizer, will also receive 0.5 of a share of New Biohaven, a new publicly traded company that will retain Biohaven’s non-CGRP development stage pipeline compounds, per Biohaven common share.

The boards of directors of both Biohaven and Pfizer have unanimously approved the transaction. Pfizer will pay transaction consideration totaling approximately $11.6 billion in cash.

Pfizer will also make payments at closing to settle Biohaven’s third party debt and for the redemption of all outstanding shares of Biohaven’s redeemable preferred stock.

The $148.50 cash consideration represents a premium of approximately 33% to Biohaven’s volume weighted average selling price of $111.70 over the three months prior to the announcement of the transaction.

The proposed transaction includes the acquisition of Biohaven’s calcitonin gene-related peptide (CGRP) programs including:

  • Rimegepant:
    • Approved in the United States (U.S.) under the trade name, NURTEC® ODT, for both the acute treatment of migraine and preventive treatment of episodic migraine
    • Approved in the European Union under the trade name, VYDURA®, for both acute treatment of migraine and prophylaxis of episodic migraine
  • Zavegepant:
    • On track for a 2Q2022 acceptance (based on March 2022 submission) in the U.S. as an intranasal spray for the acute treatment of migraine and in development as an oral soft gel for chronic migraine prevention
  • A portfolio of five pre-clinical CGRP assets

“Today’s announcement builds on our legacy of delivering breakthroughs for patients living with complex pain disorders and diseases that disproportionately impact women,” said Nick Lagunowich, Global President, Pfizer Internal Medicine.

“NURTEC® ODT, which is already the #1 prescribed migraine medicine in its class in the United States, coupled with Biohaven’s CGRP pipeline, offers hope for patients suffering from migraine worldwide.

We believe Pfizer is uniquely positioned to help the portfolio reach its full potential given our leading scale and capabilities, including comprehensive field force engagement with Primary Care Physicians, specialists and health systems delivering the right information at the right time.”

This agreement follows on the November 9, 2021 collaboration for the commercialization of rimegepant and zavegepant outside the United States, in connection with which Pfizer invested $350 million to acquire 2.6% of Biohaven’s common stock at $173 per share.

“We are excited to announce Pfizer’s proposed acquisition of Biohaven, recognizing the market leadership of NURTEC® ODT, our breakthrough all in one migraine therapy, and the untapped potential of our CGRP franchise,” said Vlad Coric, MD, Chairman and Chief Executive Officer of Biohaven. “Pfizer’s capabilities will accelerate our mission to deliver our migraine medicines to even more patients, while the new R&D company is well positioned to bring value to patients and shareholders by focusing on our innovative pipeline for neurological and other disorders. We believe this transaction represents significant future value creation for patients and our collective shareholders.”

Following the closing, New Biohaven will continue to operate under the Biohaven name.

New Biohaven will be led by Vlad Coric, MD, as Chairman and CEO, and include other members of the current management team of Biohaven.

Biohaven common shareholders will receive, for each Biohaven share, 0.5 of a share of New Biohaven distributed via a pro rata distribution of SEC-registered, publicly listed shares.

At distribution, New Biohaven will be capitalized with $275 million of cash. New Biohaven will also have the right to receive tiered royalties from Pfizer on any annual net sales of rimegepant and zavegepant in the United States in excess of $5.25 billion.

Pfizer expects to finance the transaction with existing cash on hand.

Pfizer’s acquisition of Biohaven is subject to the completion of the New Biohaven spin-off transaction and other customary closing conditions, including receipt of regulatory approvals and approval by Biohaven’s shareholders.

The companies expect the transaction to close by early 2023.

Due to the proposed transaction, Biohaven will not hold a conference call to discuss its first quarter 2022 financial results and will issue a press release and file a quarterly report on Form 10-Q with the U.S. Securities and Exchange Commission announcing those results on May 10, 2022.

J.P. Morgan acted as Pfizer’s financial advisor for the transaction with Ropes & Gray LLP acting as its legal advisor. Centerview Partners acted as Biohaven’s financial advisor for the transaction with Sullivan & Cromwell LLP acting as its legal advisor.”

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-acquire-biohaven-pharmaceuticals

1...181920...156Page 19 of 156

EDITOR PICKS

POPULAR POSTS

POPULAR CATEGORY

ABOUT US

LifeProNow provides guidance and high quality contents to help job seekers to get their dream Job. All the contents are written by experienced folks and peer reviewed by experts.

Contact us: [email protected]

FOLLOW US

© LifeProNow | All Rights Reserved