By Kim Coghill
An HIV protease inhibitor being tested by Vertex Pharmaceuticals Inc. for once-a-day dosing entered Phase III clinical trials.
The product, VX-175 (also known as GW433908), is a prodrug of the approved protease inhibitor Agenerase (amprenavir) and is licensed to Glaxo Wellcome, of Research Triangle, N.C., in the United States, Europe and other countries. Glaxo Wellcome is responsible for product formulation and manufacture of VX-175, design and implementation of clinical trials, and regulatory submissions. Vertex retains co-promotion rights.
VX-175 has been formulated for a dosing regimen in clinical trials of three pills twice daily, and has the potential for once-daily dosing.
Vertex's first approved product, Agenerase, also promoted by Glaxo Wellcome, is an HIV protease inhibitor that is taken in eight-pill doses twice daily.
"The difference between Agenerase and VX-175 is that there's a minor chemical modification to the new drug that allows it to be formulated in a more compact way," said Michael Partridge, associate director of corporate communications for Cambridge, Mass.-based Vertex. Upon approval, VX-175 will replace Agenerase.
VX-175 will undergo two separate 48-week, Phase III pivotal trials.
Study 30001 is an open-label, randomized study comparing three tablets of VX-175 dosed twice daily with the protease inhibitor nelfinavir dosed twice daily in patients who have not previously received antiretroviral therapy. All patients will receive the reverse transcriptase inhibitors abacavir and 3TC twice a day. The trial will enroll 210 patients at more than 30 centers in the United States and will assess the safety and antiviral efficacy of each regimen.
Study 30002 also is an open-label trial and will enroll more than 600 HIV-infected patients at 50 research centers worldwide who have not previously received antiretroviral therapy. Patients will be randomized to receive either a combination of three tablets of VX-175 and ritonavir once a day, or 1250 mg of nelfinavir twice a day. Each patient also will receive abacavir and 3TC twice daily. A Phase III study in treatment-experienced patients is planned for 2001.
Partridge said the completion date is dependent upon the speed of patient enrollment. "But it is possible, for example, for a [new drug application] to be filed in 2002," he said.
Agenerase was introduced in April 1999 and currently has about 8 percent (14,000 patients) of the market share in the United States, Partridge said. In October, Glaxo Wellcome received approval from the European Commission to market the product in all 15 countries of the European Union. A $3 million milestone payment related to that approval was to be paid to Vertex this quarter.
"Agenerase has done quite well despite the flat or declining market for protease inhibitors," Partridge said.
He attributes the declines to physicians becoming less aggressive in treating patients in the early stages of infection.
Vertex has 12 other drug candidates in development to treat viral diseases, inflammation, cancer, autoimmune diseases and neurological disorders.
Vertex's VX-497, for hepatitis C, is expected to enter Phase III trials next year. VX-497 is an inhibitor of inosine monophosphate dehydrogenase, a cellular enzyme that is essential for production of guanine nucleotides, one of the building blocks of RNA and DNA.
Vertex's stock (NASDAQ:VRTX) closed Monday at $73.625, up $8.68, or 13 percent.