Hemispherx Biopharma Inc. achieved its primary endpoint in a pivotal Phase III trial of Ampligen to treat chronic fatigue syndrome (CFS), giving the Philadelphia-based company the data it needs to seek approval in the U.S. and internationally.

Patients received Ampligen for 40 weeks and gained a statistically significant increase in physical performance on a treadmill as compared to patients receiving placebo.

"One of the things I'm personally very pleased about with this study is this is actually the first time a pivotal study in this disease category has actually reached its primary endpoint," said William Carter, chairman, president and CEO of Hemispherx.

Ampligen, which acts as an immunomodulator and antiviral, is part of a new double-stranded RNA drug class aimed at treating CFS. It is believed to modulate the immune system and inhibit virus directly. In addition to the Phase III trial in CFS, it is being studied in two Phase IIb trials to treat HIV/AIDS. The product has orphan drug status in the U.S.

A new drug application filing could occur later this year, although Carter declined to give a specific timeline. Best-case scenario: Ampligen could be on the market in 2005, with a Hemispherx sales force selling it directly to specialty physicians, assuming priority review of the NDA and an approval. The company also plans to file for approval with certain international regulatory authorities.

Carter said companies such as Indianapolis-based Eli Lilly and Co. and Shire Pharmaceuticals Group plc, of Basingstoke, UK, as well as the National Institutes of Health and Johns Hopkins University, have conducted CFS compound studies, all of which failed to meet their endpoints.

"This tells you that the achievement in this disease category is very challenging," Carter told BioWorld Today. "It's got a very high barrier because unlike HIV or hepatitis C or B, where you have a proven ideologic agent, we don't have such a proven ideologic agent in this disorder yet."

Carter, who co-invented Ampligen, said Hemispherx has spent more than $100 million developing the technology for the better part of 10 years. He believes the market potential is significant, considering a wide range of medications currently are used to treat the symptoms of CFS.

CFS is a debilitating disease affecting more than 1 million people in the U.S. and Europe combined. Those patients suffer from disabling fatigue associated with flu-like symptoms, such as headaches, sore throat and muscle pain, mental fogginess, depression and sleep disorders. There are no FDA-approved therapies specifically for the condition.

"Generally, one can assume that this disease is having a very significant impact on the medical economics of the U.S.," Carter said.

To keep the Ampligen value in-house, Hemispherx intends to build its own sales force, marketing to medical specialists who would prescribe long-term medication for a disease such as CFS. It also would use distributors to help with reimbursements of the product's costs.

"We have partners in certain non-U.S. markets, in Canada and certain European countries, and we have partnerships in parts of Africa and South America," Carter said. "But we've deliberately decided to maintain the marketing rights for this disorder in the U.S."

The Phase III study was a double-blind, placebo-controlled trial evaluating Ampligen 400 mg, given twice weekly, vs. placebo. The trial randomized 234 patients at 12 U.S. centers to assess the effects of 40 weeks of treatment, with improved physical performance as the primary endpoint as measured by Treadmill Exercise Tolerance Testing.

Statistical significance was reached by patients who showed a medically significant increase - greater than or equal to 6.5 percent - in mean exercise duration. Patients taking Ampligen improved their exercise treadmill duration by more than twice the minimum considered medically significant, and the drug was well tolerated.

Specifically, patients receiving Ampligen improved exercise treadmill performance by 19.4 percent, as compared to 5.1 percent in the placebo group. Similar results were found in an intent-to-treat analysis, which included patients who completed less than 40 weeks of Ampligen treatment. Those patients showed a 17.7 percent improvement, compared with 4.3 percent of patients receiving placebo.

As for serious adverse events, there was no significant difference between Ampligen and placebo.

The FDA's Antiviral Advisory Committee previously reviewed the study design, and the Centers for Disease Control and Prevention recommended the case definition of CFS.

"The primary endpoint was substantially agreed upon by the various parties prior to commencing this trial, and this particular endpoint - physical performance as measured by treadmill duration - is one that has been largely time-honored by regulatory agencies worldwide in trying to evaluate potential recovery from chronic debilitating disease associated with limited capacity for movement," Carter said.

Hemispherx presented results from the Ampligen study Monday at the 17th International Conference on Antiviral Research in Tucson, Ariz.

Aside from Ampligen, Hemispherx has one marketed product, Alferon N, which was acquired in March 2003 from New Brunswick, N.J.-based Interferon Sciences Inc. The injectable formulation of natural alpha-interferon was approved in October 1989 for venereal warts. At the preclinical stage of development, Hemispherx is studying Oragens through a strategic relationship with Temple University, which provided the company with an oral formulation of a group of potential antiviral drugs.

Hemispherx's stock (AMEX:HEB) fell 5 cents Monday to close at $4.65.