Monsanto and Pfizer Battle Merck To Launch the First COX-2 Inhibitor

21 December 1998 00:00  [Source: ICB Americas]

By Feliza Mirasol

Celebrex (celecoxib) and Vioxx (rofecoxib), the two cyclo-oxygenase enzyme (COX-2) inhibitors by Monsanto's G.D. Searle unit and Merck & Co., respectively, are drawing praise from analysts who have high expectations for each drug's performance in the arthritis market. Monsanto has now taken the lead in the race to commercialize the first drug of this type.

Analysts believe that both products will be highly successful. ABN-AMRO analyst James Keeney says that even with Monsanto's developmental lead, the products remain a toss-up as to which will have a better position in the marketplace.

Merck submitted a new drug application (NDA) for Vioxx to the Food and Drug Administration last month (CMR, 11/30/98, pg. 19). In contrast, Monsanto and its co-promotion partner, Pfizer Inc., received a recommendation for approval from an FDA advisory committee early this month (CMR, 12/7/98, pg. 22).

"Both [Pfizer and Merck] have good name recognition in the industry as well as strong marketing forces," says Susan Capps, senior manager of pricing studies at Plymouth Meeting, Pa.-based IMS Health. "I think these products will be very welcome by the market if they truly work the way studies have shown. Anything that prevents side effects [such as ulcers] will definitely play a big part in prescription and customer use."

Both products have been shown to effectively manage arthritis pain, much like traditional non-steroidal anti-inflammatory drugs (NSAIDs). But unlike traditional NSAIDs, they do not cause gastrointestinal (GI) side effects, a benefit that is expected to give this new class of NSAIDs substantial headway in the arthritis and therapy market.

"All the products heretofore have had interference with the gastrointestinal tract in producing ulceration and gastritis in sensitive individuals, whereas these drugs don't have that side effect," Mr. Keeney says. "That's the key. They don't relieve pain or inflammation any better, but they don't have that side effect."

Because of their high selectivity, celecoxib and rofecoxib can block COX-2, which is activated upon injury and proceeds to synthesize prostaglandins involved in inflammation, while not blocking the constitutive form of the same enzyme, COX-1, according to published reports.

COX-1 synthesizes the prostaglandins that protect the lining of the GI tract and maintain normal platelet and kidney function. Inhibition of this enzyme accounts for many NSAID side effects, particularly those associated with GI damage.

Both drugs were filed for the treatment of osteoarthritis and the management of arthritic pain. However, Celebrex's filing also includes the treatment of rheumatoid arthritis whereas Vioxx's does not. In addition, both are oral tablets. Rofecoxib is a once-a-day treatment and celecoxib is a twice-a-day treatment.

Analysts predict strong sales for both products. According to a report by Paine-Webber analyst Jeff Chaffkin, US sales of Vioxx could reach $125 million next year, $500 million in 2000, $750 million in 2001 and $1 billion in 2002. Non-US sales could total $100 million in 2000, $200 million in 2001 and $300 million in 2002.

Other analysts estimate higher sales. "We think that both products could sell $500 million next year. In fact, we could be accused of being conservative," says Mr. Keeney. He anticipates sales of $1.3 billion and $1.8 billion for Merck's Vioxx in 2000 and 2001. "And that might even be disappointing to some people," he adds, pointing out that many project even higher levels.

Although he does not track Monsanto, Mr. Keeney expects Celebrex to have similar sales, implying a total market for the two products of $2 billion to $3 billion in the year 2000.

Decision Resources, a Waltham, Mass.-based healthcare research and consulting firm, projects that if Celebrex can maintain a low-bleed profile, it could have sales of $500 million to $1 billion within three years of its launch. Its peak sales could approach $1.5 billion to $2 billion in 2003.

At a recent analysts meeting, Merck reported that the current market for prescription NSAIDs is static at around $2.6 billion, but 60 percent of sales come from off-label, generic products. As a result, analysts expect that this new class of drugs will "break open" the arthritis therapy market, following a trend noted in several other markets. Mr. Keeney cites as precedence Prozac's (Lilly) entrance into the anti-depressants market and Respidol's (J&J) entrance into the anti-schizophrenia market.

AZIMILIDE--Procter & Gamble Pharmaceuticals has submitted a NDA with FDA for azimilide, its investigational anti-arrythmic drug. The company is seeking an indication for the maintenance of sinus heart rhythm in patients who have irregular heartbeat.

CYTOMEGALOVIRUS Immune Globulin--Gaithersburg, Md.-based MedImmune Inc. has received FDA approval for an expanded indication of CytoGam (cytomegalovirus Immune Globulin Intravenous, human), also known as CMV-IGIV. CytoGam is now indicated for prophylaxis against cytomegalovirus disease associated with kidney, lung, liver, pancreas and heart transplants.

NYSTATIN--Abbott Laboratories has signed a licensing agreement with Aronex Pharmaceuticals Inc., a Woodlands, Tex.-based biopharmaceutical company, to commercialize Nyotran, Aronex Pharmaceuticals' proprietary injectable formulation of nystatin for the treatment of systemic fungal infections. Payments under the agreement include upfront payments, milestones and developmental support. Aronex Pharmaceuticals will also receive royalties based on product net sales following product launch.

Under a related stock purchase agreement, Abbott will purchase 837,989 shares of Aronex Pharmaceuticals common stock for $3 million in cash. Abbott's total payments to Aronex Pharmaceuticals, under both agreements, could total up to $40 million, exclusive of royalties on product net sales.

OMEPRAZOLE--Astra AB has signed an agreement with Schering-Plough Corporation to reacquire from Schering-Plough's subsidiary, Essex Chemie, the rights to market Losec (omeprazole, anti-ulcer) and Perfudal/ Prevex (felodipine, anti-hypertension) in Italy and Spain. In exchange, Essex Chemie will receive payments and revenues from Astra based on sales. The agreement is effective January 1, at which time Astra will make payments to Essex Chemie for a minimum period of five years.

QUININE--The Defense National Stockpile Center has awarded roughly 158,000 av. oz. of quinine sulfate to Rambach Corporation, Newark, N.J., at an approximate market value of $111,000.

RIBAVIRIN--FDA has approved Schering-Plough's Rebetron Combination Therapy containing Rebetol (ribavirin, USP) capsules and Intron A (interferon alfa-2b, recombinant) injections for the treatment of chronic hepatitis C. The treatment is for patients who have compensated liver disease previously untreated with alpha interferon therapy.

ROSIGLITAZONE MALEATE--SmithKline Beecham has submitted a marketing authorization application to the European Agency to market Avandia (rosig- litazone maleate), an investigational drug for the treatment of type II diabetes.

SELEGILINE HYDROCHLORIDE--Food and Drug Administration has approved Ivax Corporation's selegiline hydrochloride 5 mg tablets for use as an adjunct in the management of Parkinson's disease. Ivax's product is the generic equivalent of Eldepryl, by Somerset Pharmaceuticals Inc. Zenith Goldline Pharmaceuticals Inc., Ivax's wholly owned subsidiary, will market the product.

THALIDOMIDE--Rockville, Md.-based EntreMed Inc. has signed a collaborative sublicensing agreement with Warren, N.J.-based Celgene Corporation to advance the development of thalidomide (anti-autoimmune and anti-inflammatory). The agreement gives Celgene exclusive worldwide rights to EntreMed's patents and technology for the drug, as well as FDA orphan drug designations achieved by EntreMed.

THYROTROPIN--Genzyme General has received marketing approval from FDA for Thyrogen (thyrotropin alfa for injection), an adjunctive diagnostic tool for use in the follow-up screening of patients treated for thyroid cancer. Genzyme will begin marketing the product immediately in conjunction with Knoll Pharmaceuticals Company, Mount Olive, N.J.

VERAPAMIL HYDROCHLORIDE--FDA has approved Elan Corporation PLC's Verelan PM, a chronotherapeutic form of verapamil hydrochloride, for the management of hypertension. Schwarz Pharma Inc., the US affiliate of Monheim, Germany-based Schwarz Pharma AG, will market and distribute the product in the US following its anticipated launch in the first quarter of 1999.

P53 GENE--Schering-Plough Research Institute reported the interim results of ongoing phase I clinical studies of its recombinant adenovirus encoding human p53 gene therapy at the Seventh International Conference on Gene Therapy of Cancer held in San Diego, Calif.

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