Vertex Pharmaceuticals Inc. and Burroughs Wellcome Co. arejoining the protease inhibitor field a little later that some of theircompetitors, but that may have helped position the partners as strongplayers in the area.

Vertex and Burroughs Wellcome said Tuesday that they started PhaseI trials of VX-478, an orally available protease inhibitor, to treat HIVand AIDS. The trial will assess the compound in 18 HIV-positivepeople at a single site in North Carolina. The dose-escalation study isdesigned to test the tolerability, pharmacokinetics and bioavailabilityof VX-478.

"Vertex did enter the research later than the other players," said LynnBrum, the Cambridge, Mass. company's director of corporatecommunications. "Perhaps we had an advantage identifying some ofthe issues they saw in the clinic. In developing the compound, wefocused on its oral bioavailability and potency, and we alsoconsidered the eventual manufacture of the compound in selecting alead, which became VX-478.

"The result," she told BioWorld, "is a compound we think is amongthe most potent, bioavailable and well-tolerated that have been advanced into clinical development."

Furthest ahead in the development of protease inhibitors for HIV areMerck & Co. Inc., of Whitehouse Station, N.J.; Hoffmann-La RocheInc., of Nutley, N.J.; and Abbott Laboratories, of Abbott Park, Ill.Products from those companies, while in later-stage trials, have haddifficulties associated with manufacturing, oral bioavailability and/ordose-limiting toxicities.

David Stone, a managing director at Cowen & Co. in Boston, saidclinicians, the FDA and patients all are excited about the class.Protease inhibitors, with a potentially better safety profile thanreverse transcriptase inhibitors, for example, could be usedcontinuously, and earlier in the disease stage, helping to slowreplication of the virus.

`The reason to be excited about VX-478," Stone told BioWorld, "isit's easy to make, it's easy to give _ at least it looks that way [inanimal studies] . . . it's highly bioavailable by oral administration andthere doesn't appear in animals to be any toxicity limits up to veryhigh doses. In terms of properties, it's very well positioned."

Agouron Pharmaceuticals Inc., of La Jolla, Calif., recently completeda Phase I study of its protease inhibitor, AG1343. The company lastmonth reported favorable safety and pharmacokinetic results, andsaid it quickly was going into a small, pilot Phase II study.

Stone said Agouron's product has advantages similar to Vertex'swhen compared to the later-stage product candidates. Agouron alsohas an edge in that AG1343 has been tested in humans.

One factor, however, that causes Stone to lean toward Vertex ishaving a partner in Burroughs Wellcome, which sells AZT, currentlythe main therapy for HIV. Kissei Pharmaceutical Co. Ltd., of Japan,also is partnered with Vertex on VX-478, and has rights in Japan andChina. Kissei filed for clearance for a Phase I trial in Japan to testVX-478 in healthy volunteers, Brum said.

Agouron, meanwhile, is developing AG1343 in collaboration withJapan Tobacco Inc., which lacks the pharmaceutical experience ofBurroughs Wellcome and Kissei.

Stone said Burroughs Wellcome plans to test VX-478 later this yearin Phase I/II studies alone and in combination with reversetranscriptase inhibitors. He went on to say that pivotal efficacystudies could begin in 1995, and given the drug's safety profile,sufficient data could be available for a new drug application filing in1996.

Vertex's stock (NASDAQ:VRTX) closed Tuesday, unchanged, at$15.75 per share. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.

No Comments