Hyperion Hits Goal in Trial for Rare-Disease Drug, Prepping FDA Application

Hyperion Therapeutics raised $60 million in venture capital a year ago, and it should be in a position fairly soon to generate some return on that investment.

The South San Francisco-based biotech company said yesterday its experimental drug met its primary goal in a pivotal study including 46 patients with a rare phenomenon known as urea cycle disorders. The pivotal study, which the FDA signed off on in advance, should enable the company to file an application for U.S. approval of the drug before the end of next September, says Christine Nash, Hyperion’s vice president of marketing.

Treatments for rare diseases have come back into fashion this year, which my colleague Ryan described earlier this year. Even in the era of cost containment and healthcare reform, drugs for diseases affecting only a few thousand people, but which really do improve people’s lives, can still command huge payments from insurers. It’s also harder for generic competitors to swoop in to grab market share with rare-disease drugs, like they often do with conventional mass-market pharmaceuticals. Drug giant Sanofi-Aventis, knowing this all too well, has moved aggressively to acquire the standard-bearer for rare-disease companies—Cambridge, MA-based Genzyme—for $18.5 billion. Genzyme has said that price is too low.

For its part, Hyperion has developed a new drug for urea cycle disorders, which it estimates afflict about 2,000 people in the U.S., about half of whom have been diagnosed and treated. The market for this treatment is thought to be in the “$200 million-ish” range, Nash says.

Before diving into the weeds with the clinical trial data, I first wanted to know more about the company’s history, the medical problem it’s tackling, the standard of care today, and what Hyperion has that’s really any different. I figured it was worth checking in, since some familiar investors—including Bay City Capital, Sofinnova Ventures, Panorama Capital, Highland Capital Partners, New Enterprise Associates, and WRF Capital—have all thrown capital behind the idea.

Hyperion was founded in 2007 when it acquired the rights to glycerol phenybutyrate (HPN-100) from Ucyclyd Pharma, a subsidiary of Scottsdale, AZ-based Medicis Pharmaceutical (NYSE: MRX), a company better known for the anti-wrinkle injection Restylane than for the treatment of rare diseases.

The problem with urea cycle disorders, in concept anyway, is pretty to understand. These patients lack certain enzymes that clear waste nitrogen from the bloodstream. Such waste builds up every time we eat protein; if it doesn’t get cleared, it causes nerve damage.

Johns Hopkins researcher Saul Brusilow did pioneering work that led to the development of the first treatment for patients with this disorder, a drug called sodium phenylbutyrate (Buphenyl). The treatment, Nash says, “has been a true lifesaver,” for patients with urea cycle disorders.

But you knew there would be a catch, right? Adults on the existing drug have to take about 40 vitamin-size pills per day, and the drug tastes and smells bad. The dose is tailored based on weight, so children don’t have to take quite as much, but parents often find it hard to get their kids to take the medicine, Nash says.

So Hyperion’s goal is to see if it can do better with a lower dose formulation, taken in three teaspoons per day, that has no taste or smell, Nash says.

The trial whose results Hyperion unveiled yesterday was conducted with a special protocol assessment with the FDA, essentially a written agreement that said this single study, should it prove successful, ought to provide a sufficient for market approval of the drug, Nash says. The goal was to show that the new drug was considered “non-inferior” to the existing product.

The main measurement of effectiveness was how much ammonia was found in patients’ blood at days 14 and 28 of treatment. At the end, researchers found that patients on the new drug had, on average, 34.7 micromoles per liter of ammonia in their blood, while those on the older treatment had a higher level, 38.4 micromoles per liter. The result is noteworthy because doctors consider 35 micromoles per liter to be the “upper end of normal” for ammonia concentration in the blood, Nash says.

The most common side effects reported in the study were diarrhea, flatulence, headache, vomiting, fatigue, lack of appetite, and stomach pain, Hyperion said. More detailed results are expected to be presented at the American College of Medical Genetics meeting, or the Society of Inherited Metabolic Disorders conference, before the end of March, Nash says. Findings will also be published in a peer-reviewed scientific journal, she says.

The regulatory pathway for Hyperion’s drug should be pretty straightforward, as Nash assured me the company has had no indication that the FDA will require more clinical trials—as it often does with drugs for common conditions such as diabetes or obesity. If talks go well with the FDA, and the agency clears the product for sale, Hyperion will move ahead with plans to market the drug itself to this small, manageable population of patients and doctors.

“We are familiar through the clinical trials with many of the key physicians,” Nash says. “And as we’ve seen in other small markets, when new treatments come along, there’s often new interest and increasing diagnosis of these patients.”

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