Vertex Pharmaceuticals Inc. and its partner, Glaxo Wellcome plc,said a clinical study of Vertex's protease inhibitor, VX-478, forAIDS demonstrated the drug's anti-HIV effect increased as the doseescalated and the compound was safe at all dosage levels.
The Phase I/II trial data, which evaluated VX-478 in 42 patients over28 days as a monotherapy, showed patients who received the largestdose, 1,200 mg two times daily, experienced a 99 percent medianreduction in viral load, which is the amount of HIV in the blood.Patients taking the largest dose also saw a median CD4 countincrease of 110.
Joshua Boger, Vertex's president and CEO, said the datademonstrates VX-478 as a single drug is as potent as or more potentagainst AIDS than other protease inhibitors.
Although Glaxo, of London, and Vertex, of Cambridge, Mass., aretargeting VX-478 for use in combination with other antiviral drugs totreat AIDS, the Phase I/II data were so encouraging the companiesare launching a broader Phase II study to test VX-478 as amonotherapy. (See BioWorld Today, Sept. 16, 1996, p. 1.)
Data on Vertex's protease inhibitor were presented at the 36th annualInterscience Conference on Antimicrobial Agents and Chemotherapy(ICAAC), in New Orleans, Monday.
Within the last 10 months, the FDA has approved protease inhibitorsmade by Roche Holding Ltd., of Basel, Switzerland; AbbottLaboratories, of Abbott Park, Ill.; and Merck & Co. Inc., ofWhitehouse Station, N.J.
Of the three marketed protease inhibitors, those made by Merck andAbbott have nearly the same anti-HIV strength and are consideredstronger than Roche's drug. However, neither Merck's proteaseinhibitor, Crixivan (indinavir), nor Abbott's drug, Norvir (ritonavir),achieved a level of potency comparable to Vertex's VX-478.
Studies have shown combinations of protease inhibitors andnucleoside analogue reverse transcriptase inhibitors, such as Glaxo'sAZT and 3TC, represent the best therapy to treat the disease.
In the crowded field of protease inhibitors, Wall Street analysts saidVertex's drug could emerge as a favorite based on potency, safetyand convenience. For example, VX-478 has demonstrated itsantiviral strength in twice daily administrations while other proteaseinhibitors are taken three times a day.
In the Phase I/II study of Vertex's protease inhibitor, patientsreceived one of four dosage levels: 300 mg twice daily, 300 mg thricedaily, 900 mg twice daily or 1,200 mg twice daily. Antiviral activityincreased with each dose, investigators said, and adverse reactionswere "generally mild."
Another ICAAC presentation Monday showed a combination ofAbbott's Norvir and Roche's protease inhibitor, Invirase(saquinavir), reduced median viral load by 99.9 percent and increasedmedian CD4 counts by 95 cells. Patients received either 400 mg ofboth drugs or 600 mg of Norvir and 400 mg of Invirase twice dailyover 12 weeks.
In addition, the study showed patients receiving either 400 mg of theRoche and Abbott drugs three times a day or 600 mg of bothcompounds two times a day for six weeks experienced median viralload drop of 99.3 percent and median CD4 cell count increase of 75.
Agouron Pharmaceuticals Inc. also is developing a protease inhibitor.The La Jolla, Calif., company's Viracept (nelfinavir) is beingevaluated in Phase II/III trials. Agouron expects to file for FDAapproval in the first quarter of 1997.
Agouron Monday said it was broadening distribution of Viracept toAIDS patients who have not been able to use one of the threemarketed protease inhibitors. The drug will be provided free ofcharge under an FDA-approved expanded access program.
More News From ICAAC
* Merck said a pilot study of Crixivan and a non-nucleoside reversetranscriptase inhibitor, DMP 266, showed the combination therapyproduced a mean reduction in viral load of 99.9 percent after 12weeks of treatment and a mean increase in CD4 counts of more than100. Patients received 200 mg of DMP 266 once daily and 800 mg ofCrixivan every 8 hours. DMP 266 is under development by DuPontMerck Pharmaceutical Co., a joint venture between Merck andDuPont Co., of Wilmington, Del.
* Gilead Sciences Inc., of Foster City, Calif., said a Phase I/II studyof GS 840, a nucleotide reverse transcriptase inhibitor, showed thedrug achieved a mean reduction of 97 percent in the amount ofhepatitis B virus in patients' blood. GS 840 also is being tested inPhase II/III trials for AIDS in combination with other antiviralcompounds, such as protease inhibitors and nucleoside analoguereverse transcriptase inhibitors. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.