FDA should accept “a reasonable likelihood of patient benefit” as the appropriate standard for approving therapies for unmet medical needs, the National Venture Capital Association and its Medical Innovation & Competitiveness Coalition contend.

“It is always possible to ask for more proof of safety and efficacy before making a decision to release a new product,” according to NVCA/MedIC proposals for improving the approval process.

The quest for more certainty delays market access, harming patients and deterring investment in innovation, NVCA/MedIC says. So “it should be made clear that the evidence of benefit required should depend on the level of unmet medical need and the likely safety risk of a new product.”

NVCA formed MedIC, a coalition of life science investors, innovators and entrepreneurs, to examine the medical innovation ecosystem and determine how it can be revitalized.

Having determined where changes are needed, the group now is seeking support for them on Capitol Hill and among other stakeholders, such as patient advocacy groups.

Leaders at the House Energy and Commerce Committee indicated their willingness to examine the venture capitalists’ contentions during a July 7 hearing that began the debate on reauthorization of the Prescription Drug User Fee Act with the focus on medical innovation, jobs and patients (Also see "Woodcock Defends Speed Of FDA Reviews, Cites 20 Approvals In First Half Of 2011" - Pink Sheet, 7 July, 2011.).

The NVCA/MedIC efforts coincide with those of the Biotechnology Industry Organization, which released its own proposals June 29 to revitalize medical science investment through improved operations at FDA (Also see "BIO’s "Big Ideas" For FDA Reform Are Too Big For PDUFA" - Pink Sheet, 4 July, 2011.) and tax incentives (see story, Also see "Tax Incentives To Spur Innovation: BIO's "Big Ideas" Beyond FDA" - Pink Sheet, 11 July, 2011.

Balancing Risk And Efficacy

Restoring balance to the benefit/risk ratio used to assess medical products is one of NVCA/MedIC’s key goals.

The agency has moved to a position in which its requirement for substantial evidence of efficacy is analogous to the proof beyond a reasonable doubt required in criminal trials, NVCA board member and Warburg Pincus Management Director Jonathan Leff said in an interview.

That standard fails to account for the trade-offs that are acceptable when a disease is life-threatening or life-altering and there are no available therapies, he said.

In such instances, he suggested, it is appropriate to use “a standard of preponderance of the evidence, where a reasonable person, taking into account all of the available clinical data, can conclude that it is likely that a product is going to provide more benefit to patients than risk.”

There is a more balanced assessment of risk and benefit in Europe, Leff contended.

As an example, he cited InterMune’s Esbriet (pirfenidone). The drug was approved for idiopathic pulmonary fibrosis by EMA in March following a positive recommendation from its Committee for Medicinal Products for Human Use (Also see "Pleasant Surprise For InterMune With Early Positive Opinion On Pirfenidone From CHMP" - Pink Sheet, 17 December, 2010.).

Yet, Leff noted, FDA asked for a third Phase III clinical trial despite an advisory panel’s willingness to support the drug, which showed mixed results in two trials (Also see "Despite Positive Advisory Committee Vote, InterMune Gets Complete Response For Pirfenidone" - Pink Sheet, 4 May, 2010.).

EMA has approved Amylin/Lilly/Alkermes’ diabetes drug Bydureon, which is the subject of a complete response letter from FDA seeking more data, as well as a thorough Qt study, Leff added (Also see "Amylin's Once-Weekly Bydureon Clears Major Cardiac Safety Hurdle" - Pink Sheet, 7 July, 2011.).

FDA Open To New Pathways

Now appears to be a propitious moment for NVCA/MedIC’s quest for a new FDA attitude in weighing benefit and risk, and a BIO recommendation for drug reviewers to consider evidence beyond clinical trials when assessing benefit (Also see "BIO Seeks Weight-Of-Evidence Standard For Drug Approvals" - Pink Sheet, 29 June, 2011.).

FDA Commissioner Margaret Hamburg told a session at the BIO international conference in Washington, D.C., June 28 that the agency is looking at different approval pathways for different products (Also see "FDA Thinking "Seriously, Deeply" About Range Of Approval Strategies – Hamburg" - Pink Sheet, 4 July, 2011.).

NVCA/MedIC also recommends that FDA’s statutory mission be amended to include the promotion of accelerated access to novel therapies and technologies and to strengthen the role of health care providers in decision-making.

FDA should routinely assess the impact of its decisions, policies and priorities on unmet medical needs and medical innovation, NVCA/MedIC says.

Other recommendations include: placing an innovation advocate, drawn from investors or entrepreneurs, on advisory committees; establishing a well-defined regulatory pathway for approving new therapeutics and companion diagnostics or drug/device combinations; setting approval milestones for combination products.

By Cathy Dombrowski

FDA Approval Standards Need To Be Relaxed, Venture Capitalists Say

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