Companies Weigh FDA Draft Guidance on Developing Targeted Therapies for Subsets of a Disease

Regulatory NewsRegulatory News | 20 February 2018 |  By 

Sarepta Therapeutics, Merck, Illumina and industry group PhRMA have offered their support and suggested changes for US Food and Drug Administration (FDA) draft guidance to support the development of treatments that address underlying genetic mutations that often cause or contribute to diseases.

The draft guidance, released in December 2017, seeks to help companies developing certain targeted therapies on the basis of targeting a molecular subtype that is common across different phenotypes, rather than solely on an individual disease.

While the draft is written with a focus on grouping multiple molecular alterations within the same clinical disease, PhRMA recommends in its comments released Tuesday that FDA “also reflect the scenario where one or more molecular alterations occur across multiple ‘diseases’ (e.g., a single genetic mutation which occurs in tumors of different tissue types).”

The lobbying group also reiterated its encouragement for FDA’s consideration of ways to incorporate emerging genetic data and knowledge into regulatory decisions.

“PhRMA is encouraged that FDA lists real world evidence (e.g., from observational studies or registry data) as one of the appropriate sources of evidence for generating data in the postmarket setting. Recognizing that new information about the genetic or molecular basis of disease may come from clinical experience or other ‘real-world’ settings, PhRMA encourages FDA to clarify how these data sources may be used to inform regulatory decisions (e.g., clinical trial design, benefit-risk assessments, and extrapolation of efficacy),” the comment said.

PhRMA also “recommends including examples of real world data sources that could be utilized. For example, in the case of evaluating the efficacy of a drug in a rare, genetically-defined subpopulation, the use of real world data evaluating the outcomes of a similar, propensity score-matched population may be an acceptable alternative to a randomized trial.”

Sarepta Therapeutics, meanwhile, which won approval in 2016 for the first drug to treat patients with the rare genetic disorder Duchenne muscular dystrophy (DMD), said that the draft guidance “is narrower in scope than expected relative to the clarity of scope provided in the statute” of the 21st Century Cures Act.

“Sarepta urges FDA to build upon this thinking in order to more broadly capture reasoned approaches where extrapolation can be appropriately applied to streamline the continuum of drug development and approval of targeted therapies – specifically to include drugs that, while classified as different products, rely upon a shared underlying genetically targeted technology or chemistry,” the Boston-based drugmaker said.

Genomics firm Illumina called the draft guidance “timely, concise and clear,” and said it “addresses an important issue: how to demonstrate efficacy across molecular subsets within a disease, particularly when one or more molecular subsets occur at a low frequency.”

The San Diego-based company also suggested one improvement – the addition “of a section on device labeling
that would also be transparent and would standardize how diagnostic results are reported out.”

And Merck also said it strongly supported the draft guidance, adding just one comment and one question on the draft guidance: “Question: How strong should the evidence from the preliminary studies be to support a grouping strategy? Some guidance on at least lower bounds would be helpful and appreciated. Comment: The term ‘consistent’ is used frequently in certain parts of the draft guidance, but is not clearly defined. Guidance on criteria for establishing consistency (or at least lack thereof) would be helpful.”



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