The Merck-Astra connection has a "a dopamine receptor antagonist for treatment of acute and chronic schizophrenia" in Phase III U.S. trials, Merck Chairman Roy Vagelos, MD, told a meeting of the New York Society of Securities Analysts Nov. 8. Roxiam (remoxipride) is licensed from Astra by Merck in the U.S. only. Roxiam "has already been approved in Denmark, the U.K., and Luxembourg," Vagelos noted. He maintained that the drug compares favorably to haloperidol as a treatment for schizophrenia. The new product, Vagelos said, "has been shown, and also contains in the label in the U.K., to cause fewer side-effects," particularly "abnormal movement of the limbs." Roxiam is one of four Merck development projects in the U.S. which have recently reached the point of public comment by the company. "We wait until we have demonstrated human efficacy before we discuss products openly," Vagelos reminded the analysts. The Merck approach to publicizing its R&D efforts keeps a shroud over early stage work, but it contributes to the mystique of the company's development record. Because the company only begins talking about its projects relatively late in the development process, it has a higher percentage of those projects reach fruition than other companies that begin talking about products earlier. With its size and breadth of product line and development pipeline, Merck can keep the status of its early projects murky without antagonizing the financial or scientific communities. The low visibility approach, however, is causing the company some problem with its AIDS effort. For the third consecutive year, Vagelos tried to convey optimism about the company's AIDS drug development projects (and the overall industry progress), but that was made difficult by the lack of detail (see box next page). Among the most recent additions to Merck's likely candidates in human testing, Vagelos described products for three diseases: Asthma: Venzair (MK-679) has emerged as the company's leukotriene D4 antagonist commercial candidate. Vagelos reported that the drug "is currently in Phase II trials." He added that "if Venzair proves to be as safe and effective as we expect, it should become first-line therapy for asthma." The respiratory area is a relatively new field for Merck. Glaucoma: MK-507 (a Phase III project) is "the first carbonic anhydrase inhibitor for topical treatment of glaucoma," Vagelos said. Previous clinical studies indicate, Vagelos said, "that MK-507 can be used as either stand-alone therapy or as add-on therapy to our existing product Timoptic." MK-507 "could replace pilocarpine [Ciba-Geigy's Ocusert] as the drug of choice for combining with a beta-blocker, such as Timoptic, when greater reduction in intraocular pressure is desired." Osteoporosis: Alendronate is a once-a-day orally ingested bone resorption inhibitor for the prevention and treatment of osteoporosis. "In Phase II trials, this drug was well tolerated and highly effective," Vagelos said. It is now "early in our Phase III studies" which will be completed in two years. Vagelos said the drug has the potential to "be a general use post-menopausal osteoporosis drug." The pipeline project that continues to attract the most attention outside the company is Proscar (finasteride) for the treatment of benign prostatic hypertrophy (BPH). Vagelos told the analysts that Proscar has completed its Phase III studies. Merck plans "to file worldwide applications for the regulatory approval of Proscar in the spring of 1991." "Our Phase III clinical trials consisted of two separate 12-month studies," Vagelos reported. "Both studies were completed this summer," and Merck's analyses of the data are "90%" complete. The company anticipates that it will "present the full analysis to the scientific community" at the American Urologists Society meeting in June. Vagelos said that the Phase III studies included 1,624 patients at 76 centers worldwide. "The results: significant prostate shrinkage in a majority of patients -- by significant we mean 20% shrinkage or greater," he said, adding that "an important subset of these patients experienced significant improvement in symptoms associated with BPH." Vagelos later defined "improvement" as an average peak urinary flow increase of 3 cc per minute over a baseline of less than 15 cc/min. The Merck exec stressed the "excellent tolerability" of the drug, noting that about 1,200 of the original 1,600 patients continued therapy beyond one year. Moreover, the specifically drug related dropout rate was "only 1%-2%" because "there were no serious side effects." Merck's Phase II studies were extended an additional year after "completion" in order to evaluate the long-term effects of Proscar. Vagelos said those studies, although unblinded, "demonstrated that the prostate shrinkage and urine flow improvements were sustained over the 18 months of treatment." Merck has also begun "an additional long-term study in men with early symptoms and less-enlarged prostates to determine if Proscar can arrest the disease at earlier stages." Merck acknowledges that Proscar is not an immediate relief compound. Vagelos cautioned that Proscar's effect on symptoms is not direct: "if a patient goes on the drug and expects that he's going to have symptoms improvement in the first couple of months, he has been misinformed by the person that is giving him the drug because that cannot happen." Asked to compare Proscar to the other potential treatment for BPH, alpha blockers like Pfizer's Cardura or Abbott's Hytrin, Vagelos suggested that there may be room for both approaches. Alpha blockers, he said, are probably only useful for the treatment of BPH symptoms, whereas Proscar will actually control the disease. "Therefore, if the alpha blocker can be tolerated and is doing some good, it would be taken along with Proscar," he said. When asked to comment on how long the FDA review for Proscar will take, Vagelos quipped: "I can tell you that depends on the age and the sex of the [FDA] reviewers." Vagelos discussed three other U.S. projects. The first is close to marketing: Plendil (felodipine) for the treatment of mild to moderate hypertension, which "will be Merck's first entry in the calcium channel blocker market." Another Astra-developed product, it has already been introduced in 14 countries abroad. Merck anticipates first marketing in 1991. Another treatment for hypertension, MK-954 "is now in Phase II trials." The product "is the first in a new class of drugs, angiotensin II receptor antagonists. It also will be developed for the treatment of congestive heart failure." Vagelos said that "studies thus far indicate that the product has all the benefits and effectiveness of ACE inhibitors," with the possible improvement of eliminating "the cough experienced by a small number of patients who use ACE inhibitors." The discussion of ACE inhibitor-induced cough refers to a recent reappraisal of the frequency of that side effect. Recent studies suggest that ACE inhibitor labeling may underrate the incidence of cough. Vasotec and Prinivil labeling currently states that chronic coughing occurred in 1.3% and 2.9% of patients, respectively. Bristol-Myers Squibb's Capoten (captopril) labeling does not include data on coughing incidence, but lists it as a side effect reported after introduction. A paper presented by two researchers from the Chinese University of Hong Kong to the American Heart Association meeting in Dallas Nov. 12 indicated that, in double-blind controlled studies, chronic cough was seen in 55.6% of captopril patients, and 45.7% of enalapril patients. In response to a question about the commercial potential for MK-954 in the crowded antihypertensive market, Vagelos said "the point is that it is a new mechanism of action of drug for controlling high blood pressure and congestive heart failure, and that is an enormous market, will always be an enormous market, and those companies that have new products that have some advantages in that area will always capture a large and significant portion of that market. And I would be very nervous if I were in Merck and [someone] had this drug in another company." Also nearing the market for Merck is Varivax, a vaccine for chicken pox. "We have applied for a U.S. license for this live attenuated varicella vaccine and are providing the FDA with additional information that is required for licensing," Vagelos said. Merck is also "improving the production process for making the vaccine." He added that Merck intends to combine Varivax with its M-M-R vaccine that protects against mumps, measles, and rubella. Two of the products in Merck's pipeline, Roxiam and Plendil, are licensed from Astra under the terms of a 1982 deal which gave Merck "U.S. rights to develop and market Astra discoveries forever, in a joint venture, if a trigger amount of sales is reached by the end of 1993." Merck is "on track to do that readily," Vagelos said. The joint-venture, which is rarely listed among the big pharmaceutical deals of the last decade, has been a boon to Merck, providing Prilosec (omeprazole) and Tonocard (tocainide) as well as the current research projects. Vagelos discussed Merck's two newer, larger, joint ventures. Vagelos declined to identify any of the upcoming new products from the Merck-J&J OTC joint venture (other than to say that "development candidates include Pepcid"). He indicated that Merck would like to see the new company "do business worldwide, eventually." He also suggested a conservative growth pattern for the project, predicting that the arrangement would begin to be profitable for Merck in the mid- to late-1990. Coinciding with the public appearance, Merck announced that the DuPont joint venture has closed. "Merck and DuPont...have signed the principal agreements to establish The DuPont Merck Pharmaceutical Company, with operations of the new venture to begin Jan. 1," a Nov. 8 press release reads. "Through this agreement," Vagelos said, "we will gain access to future profits from the joint venture company's current and, most important, future products." As of Jan. 1, the new company "will have a research staff of about 1,500, a first-year R&D budget of $230 mil., a professional sales staff of 600 people, and first-year sales of an estimated $700 mil.," Vagelos reported. "This company is going to take off pretty much at a gallop," he said. The joint venture company will copromote the angiotensin II antagonist with Merck (the drug was originally developed by DuPont, and licensed to Merck in an earlier deal). Merck also "will be the first partner choice" under the agreement, should the joint venture seek a partner for any future products. Vagelos again suggested that Merck would begin to see profits from the deal in the "mid- to late-90." AIDS RESEARCH EFFORT: MERCK CHAIRMAN VAGELOS SAYS INDUSTRY IS CLOSE TO A PRODUCT We've said before that we have two approaches to the AIDS epidemic. One is to make a drug. And the approach that is being done by [Merck] is an enzyme inhibitor drug. We have an enormous effort, probably the largest ever dedicated to a single disease process going on at Merck. We are sure it will succeed at some point, [but] we just don't have a product candidate that we can discuss today. Nor do I predict that we will be number one to do that. But I will predict that we will see a product within the next couple of years. It's that close. Now from the point of view of the vaccine, we also have a major effort...along with Repligen. Merck scientists have demonstrated recently that there are specific peptides which are similar enough as you go from one strain to another of the AIDS virus that one could now theoretically start to think seriously about a vaccine because you wouldn't have to make 75 to 100 strains of this peptide, but could make maybe six or 10 or 12. And so there is a basic research effort going on very strongly in the vaccine area as well. But that will not come as fast as the drug.
Join thousands of industry professionals who rely on Pink Sheet for daily insights
Already a subscriber?
Advanz Pharma would have had to show that the European Commission’s decision to revoke Ocaliva’s conditional marketing approval risked causing serious and irreparable harm, according to lawyers from Van Bael & Bellis.
This is your final call to participate in the survey to better understand our subscribers’ content and delivery needs. The deadline is 20 September.
We are conducting a survey to better understand our subscribers’ content and delivery needs. If there are any changes you’d like to see in coverage topics, article format, or the method in which you access the Pink Sheet – or if you love it how it is – now is the time to have your voice heard.
A new pilot aims to take Brazil closer to ‘digital transformation.’
The European Medicines Agency’s chief medical officer Steffen Thistrup argued that patients are able to understand the “complex regulatory and scientific issues” that the EMA committees discuss when they assess drugs.
Monitoring the use of decentralized elements in clinical trials is a priority for the European medicines regulatory network.
Pfizer told the Pink Sheet it would work with the health technology assessment institute, NICE, with the hope of making Hympavzi available to patients with hemophilia A via the National Health Service.
