Regulatory Focus™ > News Articles > FDA Proposes 'New Pathway' to Approve Drugs for Unmet Needs

FDA Proposes 'New Pathway' to Approve Drugs for Unmet Needs

Posted 14 January 2013 | By Alexander Gaffney, RAC

The US Food and Drug Administration (FDA) plans to hold a public meeting in February to discuss the formation of a "potential new pathway" intended to bring to market new products aimed at treating serious or life-threatening conditions for which there is an unmet need.

The new pathway seems likely to take advantage of FDA's new draft guidance on enriched clinical trials, which states that small, targeted subpopulations of patients may be used as the basis of approval for a drug product so long as sponsors can justify the elimination of non-relevant variables (and with it, the "randomness" of randomized clinical trials).

A New, More Efficient Pathway

The new pathway, as envisioned by FDA, "could involve smaller and more rapid clinical trials than would occur if the drug were studied in a broader group of patients with a wide range of clinical manifestations."

The labeling for such drugs would indicate that the product is "narrowly indicated for use in limited, well-defined subpopulations in which the drug's benefits have been shown to outweigh its risks," FDA explained.

Though the newly defined approval pathway would be new, the concept for it certainly isn't, even if it hasn't been used particularly often.  The now-classic example of this is Vertex Pharmaceuticals' cystic fibrosis drug Kalydeco (ivacaftor), which was approved last year to treat patients with a specific gene defect (the G551D mutation) based on clinical trials with just 213 patients with that specific gene mutation. The drug is now in studies to treat patients with other gene mutations, as well as those with a more common form of cystic fibrosis.

FDA noted-implicitly-this approval in its guidance. "In the last two decades, major advances in molecular and cellular biology have greatly expanded our understanding of a broad range of complex disease processes and have led to major advances in the treatment of conditions such as cystic fibrosis, HIV, hepatitis C, and multiple sclerosis," it explained.

Why a New Pathway?

The need for a new approval pathway, FDA said, stems from the need to make sure that industry feels comfortable enough to invest the considerable resources required to bring a product to market and has a set of expectations that are rooted not in regulatory discretion, but in a well-defined pathway.

"In some cases, however, the resource-intensive programs needed for approval of drugs to treat a broad condition with a wide range of clinical manifestations require very large study populations and can hinder the ability to make promising new drugs available in a timely manner to subpopulations of patients with important unmet medical needs," FDA observed. Those trials can constitute the bulk cost of approval, costing upward of $100 million per trial, depending on its size, scope and aims.

Though FDA already uses a number of approval pathway add-ons, such as priority review, accelerated approval, breakthrough product designations and fast-track review, "FDA believes that it is important to explore the need for and feasibility of a new process focused on developing drugs for subpopulations of patients with serious or life-threatening conditions," particularly those caused by antibiotic-resistant bacteria, it said.

Regulators were quick to point out that indications could always be broadened later to include additional patients. For some drugs, however, broader indications would be next to impossible, particularly if there are high rates of toxicity that are only marginally acceptable in narrow, life-threatening conditions.

FDA also said it wants to experiment with the idea of the designation and use of an "appropriate logo to appear on a drug's container label," which would warn consumers and physicians that a product is only intended for the small audience for which it was approved. This could be particularly useful for antibiotic products, FDA said, due to their overuse in settings where it is not appropriate, leading to increased rates of antibiotic resistance.

Questions to be Asked

The meeting is set to look at five broader questions:

  • Is this new pathway necessary considering the other ways sponsors can get a product to market, or might alternate methods outside this particular proposal be more appropriate?
  • For which conditions and subpopulations of patients would this proposed pathway be most beneficial? Could antibiotics, in particular, stand to benefit?
  • How should regulators monitor the use of drugs approved through this pathway given that some prescribing entities have a tendency to prescribe-and companies often surreptitiously promote-medicines for uses for which they do not have regulatory approval?
  • How should FDA weight the risks and benefits of a product in regard to specific subpopulations suffering from serious or life-threatening conditions?
  • Would the use of the aforementioned logo, intended to be affixed onto a product's container, be effective at controlling the use of a product?

Regulators said the new pathway was the brainchild of the President's Council of Advisors on Science and Technology (PCAST), whose September 2012 report called for more efficient clinical trials, among other regulatory developments such as better translational tools with which to validate therapeutic targets.

As Regulatory Focus wrote at the time, the report went on to recommend that FDA study ways to incentivize important but financially unattractive targets.

The meeting will be held on 4-5 February 2013 at FDA's White Oak campus in Silver Spring, MD.

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