BETHESDA, MD 26 October 2012—In rewriting the statute on fast-track drug products earlier this year, Congress made a point of stating that new drugs addressing the "unmet medical needs" of patients with rare diseases or conditions deserve the special considerations afforded medications for serious or life-threatening conditions.

Those special considerations, say industry insiders, should benefit the numerous small populations of patients who have rare diseases.

For 20 years FDA has had the authority to accelerate the approval of drugs intended to treat serious or life-threatening conditions.

But the agency "relatively consistently" has applied that authority only to drugs intended to treat HIV infection, HIV-related diseases, and cancer, according to Emil Kakkis, chief executive officer (CEO) of California-based Ultragenex Pharmaceutical Inc.

Only a couple of times did FDA accelerate the approval of drugs targeting rare diseases, he told an audience at an October 10 forum in San Francisco sponsored by the Biotechnology Industry Organization.

One time was for sapropterin dihydrochloride, which lowers the blood level of phenylalanine in patients with tetrahydrobiopterin-responsive phenylketonuria.

Left untreated, phenylketonuria commonly leads to severe mental retardation. Treatment before the availability of sapropterin, according to the National Organization for Rare Diseases, consisted solely of a phenylalanine-restricted diet.

Kakkis was the chief medical officer at BioMarin Pharmaceutical Inc. when the company obtained FDA's approval of the drug.

"The reason we were able to get that is there was an extensive literature of clinical studies using diet therapy which we could tap into," he said. "How many rare diseases have 20 years of therapeutic data in the literature . . . from which you can validate [a biochemical endpoint]?"

In the case of sapropterin, FDA agreed to accept blood phenylalanine concentration as a surrogate efficacy endpoint for neurocognitive development.

Kakkis said the FDA Safety and Innovation Act, enacted earlier this year, directs FDA personnel handling new drug applications through the accelerated approval pathway to be more flexible in judging endpoints.

The new law encourages FDA personnel to take into account the rarity, prevalence, or severity of the condition and the availability or lack of alternative treatments when deciding whether an endpoint likely predicts a clinical benefit.

Nick Leschly, CEO of Massachusetts-based gene therapy maker bluebird bio, nonetheless described the approval process for rare-disease drugs as a challenge in general.

"When we walked into the FDA [building] to talk about the treatment of [adreno]leukodystrophy, . . . there was one neurologist who knew a little bit, and he happened to show up" for the meeting, Leschly quipped.

Adrenoleukodystrophy was the disease at the heart of the 1992 film Lorenzo's Oil.

According to bluebird bio, the current treatment option is allogeneic stem cell transplantation from an appropriate donor, if one is available.

The company is developing a gene therapy product that, with one injection, would treat the childhood cerebral form of the disease.

A separate portion of the new law may address the concern that Leschly and other speakers at the forum had regarding FDA personnel's familiarity with rare diseases. Consultations with external experts would be permissible on issues related to the review of new medications for rare diseases.

To push the new statute on "expedited" approval into practice at FDA, Congress set a one-year deadline for issuance of "draft guidance" for implementing the changes.

Congress also set a one-year deadline for turning that document into final guidance and amending the relevant regulations.

The nearly 30-year-old Orphan Drug Act defines a rare disease or condition as one affecting less than 200,000 persons in the United States.

But the act, which names amyotrophic lateral sclerosis, or Lou Gehrig's disease, as an example of a rare disease, does not explicitly specify any rare disease or condition as being serious or life-threatening.