Drug's promise revitalizes firm

A Tampa drugmaker may hold the key to treating hepatitis C.

By KRIS HUNDLEY, Times Staff Writer
Published January 4, 2008

For the past 15 years, a little-known Tampa company has been barely breaking evenwith a drug that treats gastrointestinal illnesses in children and adults.

Now Romark Laboratories hopes to prove that the same medication is effective against hepatitis C, the leading cause of liver transplants in the United States.

If ongoing clinical trials are successful, it could transform Romark's drug, Alinia, into a billion-dollar blockbuster. And it would be a breakthrough for the more than 4-million Americans with hepatitis C, which can lead to cirrhosis, liver failure and liver cancer.

With existing treatments effective only about half the time, specialists like Dr. David Heiman in Tampa are eager to find new options for their hepatitis C patients. "Anybody who shows me the next therapy is better than the current and not significantly more dangerous, I'm on board," Heiman said.

Romark was cofounded in 1993 by veteran research scientist Dr. Jean-Francois Rossignol and Tampa investment banker Marc Ayers. While working at France's Pasteur Institute in the 1970s, Rossignol developed Alinia, known generically as nitazoxanide, as an antiparasitic medication. But it wasn't until the early 1990s, after a career that included what is now GlaxoSmithKline and the World Health Organization, that Rossignol revived his discovery for use against parasitic infections in AIDS patients.

While Romark's medication worked, the demand declined in the late 1990s with the introduction of new AIDS drugs. Moving forward with clinical trials, in 2002 Romark received FDA approval for Alinia to treat diarrhea caused by parasites in children. Last year, the privately held company had about 50 employees and $20-million in revenue.

Rossignol never considered testing Alinia against viruses until he got a call from the FDA inlate 2004. Researchers using the drug on AIDS patients found their liver functions were improving. That raised the possibility that Alinia could be effective against hepatitis C, a virus that scars the liver. Hepatitis C is spread by contact with contaminated blood, such as needles shared by drug users. Patients can carry the disease for 20 years before significant symptoms develop.

Romark initiated a clinical trial of Alinia, in conjunction with the standard hepatitis C treatment, on 96 patients in Egypt in late 2004. Atthe end of 2005, Rossignol was en route to Cairo when he got a call from an excited colleague.

"Not only were patients' liver functions improved, but the decrease in the viral load was dramatic," he said. "We were able to double the cure rate."

Romark presented the results of its Egyptian trial at a major conference of liver specialists in Boston in early November. Though the data was preliminary and the strain of hepatitis in Egypt differed from the one common in the United States, the news caused a major upset in the race to cure hepatitis C.

Front-runner Vertex Pharmaceuticals of Cambridge, Mass., reported its experimental compound, telaprevir, eliminated the hepatitis C virus in 61 percent of patients. Alinia, meanwhile, had been successful in 79 percent of its Egyptian patients. Both companies tested their drugs in conjunction with the current hepatitis C treatment of interferon and ribavirin. The standard treatment has a success rate of just 40 to 50 percent.

None of the cures is cheap. The existing, two-drug combo, costs about $30,000 for 48 weeks. Romark's drug would cost an additional $30 a day; estimates of the cost of Vertex's pill, which would be taken three times a day, are not available.

Alinia's safety and apparent effectiveness have attracted the attention of researchers at Stanford University School of Medicine. Rossignol was made an affiliate faculty member at the California school and Dr. Jeffrey Glenn, a Stanford gastroenterologist and Romark consultant, is studying how the drug works.

Alinia is unique, Glenn said, because it targets the host cell, rather than the hepatitis C virus. Other companies' compounds target the virus, attempting to inhibit its ability to reproduce. But as viruses mutate, they can become resistant, making the drugs less effective. The barrier to developing resistance might be higher with a drug like Alinia that targets the host.

"Resistance is a huge problem in infectious diseases," Glenn said. "So we're not only looking for a good drug, we're looking for how to deal with resistance."

Romark is testing Alinia, in conjunction with the standard treatment, in 120 U.S. hepatitis C patients, half of whom have failed prior treatment. It expects to announce results of the trials by year end.

The company recently received $18-million from D.E. Shaw Group of New York City. Ayers and Rossignol, who remain majority owners, expect that investment to carry Romark through development of Alinia and related drug candidates. Ayers, Romark's president and chief executive, said the company also intends to open a research operation in Tampa this year, hiring 10 to 12 scientists.

After years of working virtually unnoticed by the giant pharmaceutical companies, Romark suddenly has become a contender. The two men who have nurtured the company this far scoffed at the notion that they would need help if they find themselves with a hepatitis C blockbuster.

"It's not going to be easy, but we don't feel the need for a big pharma partner," Rossignol said.

Kris Hundley can be reached at hundley@sptimes.com or (727) 892-2996.

About the drug

1970s: Romark co-founder Dr. Jean-Francois Rossignol develops Alinia as an antiparasitic medication.

1990s: The medication is used for AIDS patients. While it works, demand declines with introduction of new drugs.

2002: FDA approves Alinia to treat parasitic diarrhea in children.

2004: Researchers find the liver functions of AIDS patients using Alinia improve, suggesting the drug could be effective against hepatitis C, which scars the liver.

About hepatitis C

What is it? A virus that can lead to cirrhosis, liver cancer and liver failure.

What are the symptoms? If the virus progresses to liver disease, patients may develop jaundice, abdominal swelling and internal bleeding.