MERCK CRIXIVAN SUPPLY WILL REACH 350,000 KG IN 1998; COZAAR/HYZAAR HAVE 2% SHAREOF ANTIHYPERTENSIVE/HEART FAILURE MARKET, COMPANY TELLS ANALYSTS

The protease inhibitor Crixivan has been used by over 70,000 people in the U.S., up from 50,000 in mid-September, according to data from the primary distributor Stadtlanders. Merck presented the Crixivan figures at a Dec. 18 securities analysts meeting at the company's Whitehouse Station, N.J. headquarters.

At its launch price of $12 per day of therapy, that patient population represents an annualized total of over $300 mil. Crixivan was launched March 25, following an accelerated approval by FDA March 13 ("The Pink Sheet" March 18, p. 3).

"Demand for Crixivan is very strong, and it is doing...extremely well everywhere it has been launched," commented Merck CEO Raymond Gilmartin, noting that the drug has been taken by "more than 100,000 patients worldwide." Crixivan has the "leading market share among all protease inhibitors everywhere it has been launched," Gilmartin said.

Merck hopes to increase its manufacturing supply to a level sufficient to treat 350,000 patients annually by the end of 1997. That amount of drug represents $1.5 bil. in revenue.

To meet demand for the drug, Merck has cut design and construction schedules by half. Patients on Crixivan require one kilogram per patient per year. Merck Exec VP-Science & Technology Edward Scolnick reported that by the end of 1996 manufacturing capacity will reach more than 200,000 kg and would increase to 350,000 kg by the end of 1997.

Merck is expecting endpoint data on mortality benefits by the end of 1997. "The question is not whether it will work -- that is clear -- [but] how large the benefit will be," Scolnick declared. Merck must complete two clinical endpoint studies, study 028 and ACTG 320, to gain full approval for Crixivan. The company is also continuing a triple therapy study.

Scolnick declared that AIDS, "at least in certain parts of the world, is a manageable problem, and as more drug becomes available, it will become increasingly so." However, he stressed the need for adequate dosing of the drug to prevent viral resistance. "If you have a choice," he maintained, "you should never start with a low dose of the drug to treat this disease." If you start lower, he added, "you preclude long-term control."

Merck's osteoporosis therapy, Fosamax (alendronate), is generating over 130,000 scripts per month, the company indicated.

Merck compared the Fosamax launch to that for the cholesterol lowering agent Mevacor. In both cases the drug was viewed as a breakthrough in a common condition of aging, creating a strong initial spike of demand. Thirteen months after launch, Mevacor had roughly 100,000 scripts per month, Merck said.

Merck U.S./Canada Human Health President David Anstice noted that Fosamax is outselling Sandoz's osteoporosis drug Miacalcin by a four-to-one ratio based on days of therapy prescribed for both drugs since October 1995. "We'd like that to be higher," he maintained. As with the cholesterol category, Merck maintains that there is a vast untapped patient population for osteoporosis agents. The company believes there are 16 mil. patients with undiagnosed osteoporosis, compared to 5 mil. diagnosed and 2 mil. receiving drug treatment.

Merck filed a supplemental NDA for Fosamax for prevention of osteoporosis in April. The basis of the claim is from the Early Menopausal Interventional Trial that showed that Fosamax (5 mg/day) prevented bone loss at the spine, hip and total body and induced increases in bone mass at these sites ("The Pink Sheet" May 27, p. 8). Anstice said Merck expects FDA to act on the submission during the first half of 1997.

Merck is also expecting action on a second supplemental NDA to have fracture prevention data for hip, vertebral and wrist fractures from the Merck-funded Fracture Intervention Trial added to Fosamax labeling. The data were published in the Dec. 7 issue of The Lancet. Results from the second arm of FIT in women with osteoporosis who did not have a prior spinal fracture are expected to be available in late 1997, Scolnick said.

In addition, Merck is studying Fosamax for prevention of steroid-induced osteoporosis, males with osteoporosis, hip prosthesis loosening and prevention of periodontal disease. Scolnick noted that "the aggregate of these claims is a very large patient population over and above" the current population.

The angiotensin II inhibitor family Cozaar/Hyzaar has captured a 2% share of the hypertension/heart failure market, Anstice reported.

At 18 months since launch, the market is showing "strong acceptance" of the two products, Anstice said. The company is planning "substantial" promotional support for Cozaar, Hyzaar and the ACE inhibitor Vasotec. Merck is planning an "aggressive contracting strategy" for its second ACE, Prinivil.

Scolnick reported that "good, but surprising, data" from a trial of Cozaar in heart failure are set to be announced at the American College of Cardiology meeting in March. The drug is approved only for hypertension. Merck is also developing Cozaar for renal protection in Type II diabetics and is collecting data on endpoint reduction in hypertension that will be available at the end of the decade.

In ophthalmics, Merck reported that it holds the top three positions in the market with Trusopt (dorzolamide), launched in May 1995, its anti-glaucoma beta blocker Timoptic XE (timolol), and Timoptic with U.S. sales approaching $300 mil. and growth approaching 40%. The company is expecting to file an NDA for the dorzolamide/timolol combo Cosopt in 1997.

Merck has several other products nearing submission to FDA. The company is on the verge of filing an NDA for its 5-alpha reductase inhibitor Propecia (finasteride) for the treatment of men with male pattern baldness to increase hair growth and prevent further hair loss. Scolnick said that a 12-month trial of the drug showed that 48% of men versus 7% on placebo "had significant increase in hair." The company plans to expand the estimated market of 18 mil. by gaining a prevention indication. Unlike Pharmacia & Upjohn's Rogaine, Scolnick asserted, Propecia does not promote hair growth in "abnormal places."

Merck markets finasteride for treatment of benign prostatic hypertrophy as Proscar. Growth of the agent has leveled off at approximately $180 mil. annually in the U.S. Merck believes it can sustain growth through continued study results showing a long-term effect on prostate size and eventually through long-term prostate cancer prevention trials.

Merck is submitting an NDA for Singulair (montelukast) for the treatment of chronic asthma, including the prevention of day and night-time symptoms, in the first quarter of 1997. Scolnick said the advantages of the drug compared to Zeneca's Accolate are the drug's once daily dosing; possible use in children over six years of age; and its clean safety profile. The estimated market for the drug is about 20 mil. patients, Merck reported. Singulair will also compete with Abbott's Zyflo. Merck also plans to file an NDA for its oral migraine drug Maxalt (rizatriptan) in the first half of 1997.

Scolnick reported that plans to file Aggrastat (tirofiban) to reduce adverse cardiac events in treatment of unstable angina and angioplasty have been delayed until the second half of 1997, pending results of two clinical trials in unstable angina and angiography patients. The drug had previously failed to meet the primary endpoint in the RESTORE post-angioplasty trial.

Merck reported that its COX-2 inhibitor arthritis agent MK-966 "is now in full Phase III." The follow-on compound L-783,003 is now in Phase II trials. The drug will be dosed at 10-20 mg once daily.