Hyperion’s Pinpoint Mission Pays Off with Drug Approval

2/6/13Follow @Tansey_Xconomy

Hyperion Therapeutics (NASDAQ: HPTX) has weathered some setbacks on the way to its first drug approval, which came from the FDA last week. But many a life sciences startup would happily settle for the South San Francisco company’s timeline of progress.

Hyperion, founded in 2007, went public in July 2012, and got the FDA nod six months later for glycerol phenylbutyrate (Ravicti), a drug for a group of rare and often severe genetic disorders that prevent patients from fully metabolizing proteins. Patients afflicted with these orphan diseases, called urea cycle disorders, are unable to clear their bodies of the nitrogen in proteins by excreting it as urea. This leads to a buildup of ammonia, which can cause nervous system damage, coma, and death.

Hyperion CEO Donald Santel says the company advanced to the stage of filing a new drug application with only 13 employees and a network of consultants. The small staff faced an array of speedbumps, including litigation with its licensing partner, Medicis, and some snags at the FDA, before emerging with its first marketable product.

“We had a few near-death experiences,” Santel quips.

Now with a staff of 24, Hyperion is preparing to start selling the new drug by the end of April. Its share price has topped $19 this week, close to double its IPO price of $10 back in July.

Hyperion’s product is designed to improve on existing treatments for urea cycle disorders mainly by being less hard on the patients who take it. It provides an alternative to Medicis Pharmaceutical’s sodium phenylbutyrate (Buphenyl) pills, which not only taste bad, but also smell bad. The Medicis drug was an important step ahead for patients who had previously lacked treatments. But observers have said the pills taste like soap and smell like rancid butter.

Hyperion was founded with a pinpoint focus—to explore the potential of a single drug candidate for urea cycle disorders, which it licensed from Medicis subsidiary Ucyclyd Pharma of Scottsdale, AZ. The compound was designed todeliver the same chemical into the body as Buphenyl, but in a more palatable form.

As many as 40 times a day, patients on Buphenyl swallow the soapy-tasting pill that helps their bodies shunt ammonia out through their urine by an alternate route to the urea cycle. Hyperion’s drug uses the same alternate pathway, but it comes in the form of a clear liquid taken three times a day in amounts a bit larger than a teaspoonful.

In a pivotal trial of 44 patients, the drug controlled ammonia levels as well as the standard treatment from Medicis, Hyperion announced in 2010.

Hyperion’s formulation includes a triglyceride that the body must digest like dietary fat, which slows the release of active metabolites of phenyl butyrate into the body, says Bruce Scharschmidt, Hyperion’s chief medical officer. This means the Hyperion drug should even out the control of ammonia levels during the day and night, he says.

The FDA approved glycerol phenylbutyrate for the treatment of certain urea cycle disorders in patients over two years old whose disease can’t be managed solely by dietary changes. Those on Ravicti will still need to eat a protein-restricted diet, and possibly take amino acid supplements.

Hyperion estimates that about 2,100 people in the United States have urea cycle disorders, and about half have been diagnosed. Of those, about 575 have been taking either the Medicis drug, or they have participatedin Hyperion’s clinical trials. But the company anticipates that some patients who avoided the old drug may be willing to try the new one. The disease varies in severity, depending on the genes affected. It can be swiftly fatal in infants, while some adults can manage it with dietary changes alone.

Santel says the company is not issuing a public forecast at this point on potential Ravicti revenues or peak sales. Hyperion’s price for a year’s supply of the drug will be $250,000 to $290,000, depending on the dose indicated by the patient’s weight. The cost for the average patient taking Buphenyl is $70,000 a year, though for heavier patients taking the maximum of 40 daily pills, the price is $140,000 a year.

Hyperion secured worldwide rights to the product in March, and also has a 90-day option to acquire the older drug from Medicis, which was recently acquired by the Montreal, Canada-based Valeant (NYSE: VRX). Medicis has been focusing on drugs that have a cosmetic effect, such as Restylane, a gel injected into the skin to change the appearance of wrinkles.

Hyperion is following in the path of other orphan drug makers such as Genzyme and Biomarin Pharmaceuticals (NASDAQ: BMRN), which have shown that serving very small patient populations can be a profitable business. Health plans will reimburse for expensive drugs that treat life-threatening conditions, especially when the treatments help avoid hospitalizations.

Santel says Hyperion will develop ways to help patients get access to the drug if they can’t afford it.

“I think we’re going to do the right thing as corporate citizens,” he says.

Hyperion will probably seek a partner to market Ravicti outside the United States, Santel says.

The company has also completed a Phase 2 trial of the drug in a second indication, hepatic encephalopathy, a nervous disorder linked to liver damage or liver failure. The neurological symptoms, ranging from mild disorientation to coma, may result from toxins such as ammonia that the liver has failed to remove from the blood. The patient population for this use is much bigger. Hyperion estimates that about 140,000 people in the United States are known to suffer from hepatic encephalopathy, and about 1 million have cirrhosis, a scarring of the liver and poor liver function.

Hyperion expects to begin a Phase 3 trial in hepatic encephalopathy in 2014.

The company has raised about $160 million to date through its IPO and other fundraising rounds. Santel says the staff will have plenty to do as they prepare to start selling Hyperion’s first product, but the company suggests it may have even bigger ambitions.

“We always have our eyes open for other opportunities,” Santel says.

Bernadette Tansey is Xconomy's San Francisco Editor. You can reach her at btansey@xconomy.com. Follow @Tansey_Xconomy

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