By Lisa Seachrist
WASHINGTON ¿ The FDA granted an accelerated approval to Agenerase (amprenavir), Vertex Pharmaceuticals Inc.¿s protease inhibitor, for use in combination with other anti-retrovirals in the treatment of HIV infection.
Agenerase, discovered by Vertex, has been guided through clinical development by Glaxo Wellcome plc, of London, and will be co-promoted by the two companies once the drug becomes available in about two weeks. The new twice-daily protease inhibitor will have a wholesale cost of $16.80 per day, or $6,132 annually.
The approval triggered a $5 million milestone payment from Glaxo to Cambridge, Mass.-based Vertex.
¿We are very excited, obviously,¿ said Lynne Brum, Vertex¿s vice president for corporate communications. ¿The drug was designed using structure-based drug design, which first involves solving the structure of the HIV protease, and designing and optimizing the drug.¿
In co-promoting the drug, Vertex has a staff of 10 ¿specialists¿ who are technical experts on Agenerase and protease inhibitors in general, Brum said, adding that the corps is a start upon which a future sales force can be built.
¿This really gives Vertex visibility among infectious disease providers,¿ she said.
Agenerase was granted approval in combination with other anti-retroviral agents to treat HIV infection. The companies got the approval based on an analysis of two studies that examined Agenerase¿s role in triple combination therapy. One study pitted Glaxo Wellcome¿s reverse transcriptase inhibitors, Retrovir and Epivir, against Retrovir, Epivir and Agenerase. The other study added Agenerase to the mix of any reverse transcriptase inhibitors.
Agenerase reduced the plasma HIV RNA levels to less than 400 copies per milliliter in a significant number of patients. There are no results evaluating Agenerase¿s ability to sustain long-term suppression of HIV RNA or slow disease progression. Those data will be gathered in the post-market setting in order for the drug to receive full approval.
Boasts More-Flexible Dosing
Unlike reverse transcriptase inhibitors, which target the virus early in its replication cycle, protease inhibitors intervene late in the viral life cycle, and are the only therapies that block virus production in cells that are already infected with HIV. Since being introduced in late 1995, protease inhibitors have been largely responsible for the decrease in AIDS-related deaths and slowing of progression of the disease.
However, most protease inhibitors need to be taken three times a day, and some require the patient to fast before taking the drug. Agenerase, because of its long half-life, is taken only two times a day either with or without food. The standard dose for adults is eight, 150-milligram capsules twice a day. There is also a liquid pediatric formulation.
¿There is a much more flexible dosage design with Agenerase,¿ Brum said. ¿We think this will be an advantage to patients.¿
In addition to Agenerase, Vertex has several products in Phase II clinical development. Incel (formerly VX-710) is in five Phase II studies, testing the drug¿s ability to stymie the multi-drug resistance mechanism by which many cancers develop resistance to chemotherapy. The company is studying the drug in breast cancer, prostate cancer, ovarian cancer, soft tissue sarcoma and small-cell lung cancer.
Vertex is also conducting Phase II tests of an inhibitor of inosine monophosphate dehydrogenase, VX-497, as a treatment for hepatitis C. The drug has shown itself to have direct antiviral activity, as well as blocking liver inflammation. Its anti-inflammatory effects are the basis for Vertex testing the drug as a treatment for psoriasis. That research also is in Phase II studies.
Vertex¿s stock (NASDAQ:VRTX) closed Friday at $24.187, up $0.187.