Drug approval is a tricky business and pharmaceutical companies are facing more scrutiny regarding their drug applications than in the past.
Wyeth Pharmaceuticals, in particular, is having trouble coping with the regulations. The company is not only increasingly worried that it will lose a large chunk of its revenues to generic competition, it also faces the ongoing threat that its pipeline is starting to go dry. A further delay in the approval of its postmenopausal osteoporosis drug has become one more nail in the pharma company's coffin.
The Madison, N.J.-based pharmaceutical company said on Friday that it received an approvable letter from the U.S. Food and Drug Administration. These letters are standard practice when the agency wants more information before it can approve a drug. This is the third such letter Wyeth Pharmaceuticals has gotten about the drug, the first was in April 2007 and the second in December.
According to the company, the letter included similar requests as the letter issued in December. The FDA is looking for more information on the incidence of bazedoxifene causing strokes or blood clots. The company is seeking approval of the drug for both treatment and prevention of postmenopausal osteoporosis. A company spokesperson told Forbes.com that the FDA is forming an advisory committee to investigate the drug. Wyeth hopes the drug will be approved for both uses at the same time.
"In our conference with the Agency earlier this year, they stated their desire to convene an advisory committee to review the pending new drug applications for both treatment and prevention of postmenopausal osteoporosis," said Gary L. Stiles, M.D., executive vice president at Wyeth. "We remain committed to pursuing bazedoxifene as an important new option for the millions of postmenopausal women at risk for osteoporotic fracture."
The company said it will respond to the letter by the end of 2008.
Natixis Bleichroeder analyst Jon LeCroy said that the company is likely to get approval of the drug in mid-2009 if they are able to adequately answer all of the FDA's questions. He forecasts Wyeth being able to make $600 million to $700 million annually on bazedoxifene.
Wyeth laid off 1,200 employees in the first quarter and intends to cut 6% of its 50,000 workers by the end of the year. Up to 10% of its workforce could be cut by 2011. Wyeth also cut its sales force by 15% in 2005. The company would not comment on how many salespeople it has at the moment. (See: " Wyeth Redesigns And Re-evaluates")
During the quarter, Wyeth gained approval from the U.S. Food and Drug Administration to market a new anti-depressant, Pristiq, which hit the market this month. Pristiq has gotten a lackluster response within the industry. (See: " Forget Pristiq?")
The company lost patent protection for its blockbuster heartburn drug Protonix at the end of last year. It is set to face more generic competition for the anti-depressant Effexor later this year.
Shares of Wyeth were off 0.7%, or 32 cents, to $43.56 in afternoon trading on Friday.
Medicinal chemistry often involves making modifications to previously identified lead compounds to improve biological activity or physicochemical properties. However, to be patentable, a compound must be non-obvious in the context of prior art. So, how can it be shown whether or not it was obvious to get from one structure to another? The US Court Of Appeals for the Federal Circuit (CAFC) has recently ruled in two cases that consider this issue.
The first case was between Wyeth and Altana Pharma, and the generics company Teva. Wyeth is exclusive licensee of a patent (US4,758,579) that protects the proton pump inhibitor Protonix (pantoprazole). Teva asserted that Protonix was obvious in light of an earlierAltana patent and literature articles. The structure of Protonix is very similar to that of a compound (known as compound 12) that is described in the earlier Altana patent, but with a different substitution on the pyridine ring.
To establish obviousness in situations that involve new chemical compounds, a reason or motivation can be identified that would have led a chemist to select and modify a known compound in a particular manner to achieve the claimed compound. So, working in this framework, would it have been obvious to choose compound 12 as a lead compound, and then obvious to make the substitution?
Altana and Wyeth argued that one would not have selected compound 12 over the other approx90 compounds in the prior art, and suggested that a new compound would only be obvious if the prior art pointed to a single compound for further development efforts. But the Court disagreed, considering that compound 12 was a "natural choice", and that it was one of the more potent compounds described in the earlier patent. Moreover, the Court rejected Altana and Wyeth's 'single-compound' argument, as it would have imposed a "rigid test" in determining obviousness.
In addition, it was felt that, on the basis of literature references, one would have known what the pKa (the acid dissociation constant) should be to achieve optimal stability of the compound in the body, and it was known that this pKa value could be achieved by the substitution of a methoxy group (as contained in compound 12) for a methyl group on the carbon atom at the 3 position of the pyridine ring to arrive at Protonix. On the basis of this and other findings, the Court therefore denied Altana and Wyeth's injunction to prevent Teva selling its generic drug before the expiration of the '579 patent.
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