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Background Analysis: US FDA Advisory Committee to Review the Cardiovascular Risk Assessment of Diabetes Drugs – OCT 24-25, 2018 (EMDAC)

Announcement

The US FDA has scheduled a meeting of its Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) for Wednesday to Thursday, October 24-25, 2018. The committee will discuss the cardiovascular risk assessment of drugs for the treatment of type 2 diabetes mellitus and related FDA guidance.

Background

Description of Indication

Type 2 diabetes mellitus is characterized by insufficient insulin production from beta cells of the pancreas, combined with insulin resistance, the inability of cells to respond to normal levels of insulin, occurring in the muscles, liver, and fat tissue. The proportion of insulin resistance versus beta cell dysfunction differs among individuals with type 2 diabetes mellitus.

Approximately 29.1 million Americans have diabetes, including an estimated 8 million Americans who are undiagnosed and unaware of their condition. Among American adults, approximately one in ten suffers from diabetes, and for American adults 65 years of age and older, the number is one in four. Ninety percent of diabetes cases are type 2 diabetes mellitus.

The cause of type 2 diabetes mellitus is unknown, although genetics and environmental factors, such as excess weight and inactivity, are believed to contribute.

The classic symptoms of diabetes are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), weight loss, fatigue, blurred vision, slow healing sores, and frequent infections. The disease has been associated with increased cardiovascular disease, including ischemic heart disease and stroke, nerve damage, lower limb amputations, blindness, hypertension, and renal failure.

Regulatory Background

US Regulatory Background

In December 2008, in the context of controversy over the uncertain cardiovascular (CV) safety of Avandia (rosiglitazone), and with the support of the EMDAC from a June 2008 meeting, the FDA issued guidance for evaluating the cardiovascular (CV) risk of antidiabetic therapies to treat type 2 diabetes. The guidance required, in general, that starting in 2009, all new antidiabetic therapies should rule out an 80% or greater increased risk for major adverse CV events (MACE), based on a composite outcome of CV-related death, nonfatal myocardial infarction, and nonfatal stroke, in premarket assessment and a 30% MACE risk in postmarket assessment. This move by the FDA resulted in the conduct of several large CV outcomes trials (CVOTs) by the makers of several diabetes drugs and drug candidates. Results from some of these CVOTs have been used not only to rule out CV risk, but also to support label claims.

The potential for the upcoming EMDAC meeting to result in changes to the FDA’s approach to CV risk assessment for antidiabetic therapies was made clear by the FDA Commissioner, Dr. Scott Gottlieb, who tweeted “Over the last 10 yrs we've accrued a body of data about this topic. Join us …  to review what we've learned and consider how we should move forward with cardiovascular risk assessment for future glucose lowering therapies.” Because the focus of the meeting will be on forging a path forward for diabetes drug development, the meeting is expected to garner the interest of a wide variety of companies who are participating in, or who are considering, the development of diabetes drugs. A reduction in FDA’s requirement to conduct CV safety studies would be expected to spur development, as CVOTs have been notoriously large and costly trials. In addition, the meeting will serve to inform industry and the broader medical and patient community about what the FDA and its advisors make of a huge body of data that has amassed on the topic of CV safety of antidiabetic therapies. Details of the upcoming meeting will be revealed more fully in briefing materials for the meeting, which will be summarized on the day they are posted, in our subsequent report, the Briefing Summary.

EU Regulatory Background

On January 29, 2018, the European Medicines Agency (EMA) revised its existing 2002 guideline on the clinical investigation of medicinal products for the treatment or prevention of diabetes. The main change to the guideline involved revision of the information on the long-term safety of antidiabetes medicines, particularly the addition of a new section on CV safety, following consultation by its Committee for Medicinal Products for Human Use (CHMP) and Efficacy and Cardiovascular Working Parties (CPMP/EWP/1080/00 Rev. 2).

What’s Next?

Tarius will send a Briefing Summary after briefing materials are posted to FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA and the Sponsor’s, if applicable, briefing materials.

Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.

METADATA: Sponsor: none Drug Name: several Drug Class: none Indication: type 2 diabetes


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DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.