The FDA on Friday approved Abbott Laboratories' Norvir(ritonavir), the second in a new class of protease inhibitors, just twomonths after the company applied for permission to market the drug.
FDA Commissioner David Kessler called the decision the fastestdrug approval "in the modern era."
"We have high-powered guns and we want to make them available topatients," Kessler said, adding, "we did the review in 72 days and didnot sacrifice requirements for safety and efficacy."
Coming up quickly behind ritonavir is Merck & Co. Inc.'s proteaseinhibitor, Crixivan (indinovir), which is expected to be approvedeven quicker than the Abbott drug, and be more accepted initially bythe AIDS and medical communities. Merck, of Whitehouse Station,N.J., filed its new drug application Jan. 31, 1996, and Crixivan wasrecommend for approval Friday. (See a related article below.)
Two other promising protease inhibitors are in late stages ofdevelopment, and another _ Hoffmann-La Roche Inc.'s Invirase(saquinavir) _ was approved in December 1995. Analysts arepredicting the Merck compound and one or both of those indevelopment will be the most widely used.
Hambrecht & Quist LLC analyst Rachel Leheny said the market forprotease inhibitors, which will cost more than the reversetranscriptase inhibitors, could be $1 billion per year "because theyreally work. There's going to be a lot of people who take them andthere's talk of giving them earlier. There's a survival benefit,"Leheny said, "so there will be an increasing population of AIDSpatients."
Leheny said there probably will be a few protease inhibitors thatdominate the market, and one of them will be Merck's Crixivan, atleast for the first year.
"Merck's going to be hard to displace," Leheny said, adding that itcould get as much as 90 percent of the market early on.
The Merck compound doesn't have the interaction problems thatcause other drugs to fail to clear when used with ritonavir, analystssaid. Nutley, N.J.-based Roche's compound is less potent than theAbbott and Merck drugs.
Agouron Pharmaceuticals Inc., of La Jolla, Calif., recently started aPhase II/III program with Viracept. And Vertex Pharmaceuticals Inc.,of Cambridge, Mass., is in a multi-dose, dose-escalating Phase IIstudy with VX 478.
A number of analysts have picked up coverage of Agouron, andinvestors, who have driven the stock up considerably in the past year,also believe it will be effective. Vertex has an apparent advantage inthat it's shown it can safely go to high doses with VX 478, and it is ina good position having London-based Glaxo Wellcome plc as apartner. Glaxo markets the nucleoside analogues AZT and 3TC.
While the market will be fragmented because of the number of drugsand combinations, Leheny surmised that the Merck drug and theVertex and Agouron compounds likely will come out the winners.
Abbott's ritonavir received full approval for use alone or with suchnucleoside analogues as AZT in people with late-stage HIV disease.The FDA based its decision on studies showing that the drug booststhe number of CD4 cells that govern immunity, slows replication ofHIV, delays disease progression and reduces mortality of people withlate-stage disease.
Ritonavir also received accelerated approval for use by patients withless advanced disease, based on Abbott's written commitment to"provide additional data on patients treated for longer periods oftime, to study the durability of response and to conduct pediatricstudies."
Abbott's commitment satisfies many complaints expressed Thursdayby the FDA's Antiviral Drugs Advisory Committee whichrecommended ritonavir be approved only for use in patients withadvanced AIDS, until the company provides protocols for studiesexamining the performance of the drug in patients with earlier stagesof the disease.
"We will provide long-term follow-up safety and clinical endpointdata from ongoing studies . . . to assess the comparative clinicalefficacy and safety data in patients with advanced disease vs. patientswith early-stage disease," said Andre Pernet, vice president ofresearch and development, at Abbott, of Abbott Park, Ill.
Kessler also said that President Clinton on Friday requested anadditional $52 million from Congress to supplement the AIDS drugAssistance Program, which helps states reimburse uninsured andunderinsured AIDS patients for the cost of their treatment.
He said the president's action was taken to counteract shortfalls thatmay develop as a result of the growing use of combination therapiesusing new drugs like protease inhibitors. Whether a savings-hungryCongress will appropriate the funds to comply with the president'srequest is an open question. _ Steve Sternberg contributed to thisreport. n
-- Jim Shrine
(c) 1997 American Health Consultants. All rights reserved.