Battles over drug patents expand to biotech arena
By John George
Philadelphia Business Journal
[The article demonstrates if nothing else the problems journalists run into when small speciality pharmas are called biotechs. Provigil is definitively a small-molecule based drug and the same seems to hold true for Periostat]
As the biotechnology industry matures, a growing number of companies are finding themselves facing a new competitor: generic drug manufacturers.
Once viewed primarily as a thorn in the side of Big Pharma, but an ally of cost-conscious health insurers, generic drug maker are increasingly seeking approvals for generic equivalents of products made by biotech companies.
Locally, two biopharmaceutical concerns -- West Chester-based Cephalon Inc. and CollaGenex Pharmaceuticals Inc. of Newtown -- are engaged in efforts to protect the intellectual property rights of their flagship products from generic competitors.
Both companies filed patent infringement suits earlier this year: Cephalon for Provigil, its narcolepsy treatment, and CollaGenex for Periostat, a gum disease therapy. Both are also developing new and improved formulations of their drugs to preserve market share.
"The drug business is all about patenting your products and selling your products under patent protection," said Frank Baldino Jr., the founder, chairman and CEO of Cephalon. "Unfortunately, patents don't last forever. You know when your patents are running out, or can be threatened, so what you do is build your business so as to mitigate the impact [of losing a patent battle]. We believe we have a very strong patent position for Provigil, but we've seen pharmaceutical companies with seemingly insurmountable patents lose. You can never guess what a judge or jury will say. ... It's all part of doing business in the pharmaceutical world."
Provigil was approved by the Food and Drug Administration in 1998 as a treatment for the excessive daytime sleepiness associated with narcolepsy. Cephalon is seeking FDA approval to expand the drug's label to include its use as a treatment for adults suffering from disorders where excessive sleepiness occurs.
In March, Cephalon sued four generic drug companies -- Teva Pharmaceuticals USA Inc., Mylan Pharmaceutical Inc., Ranbaxy Pharmaceuticals Inc., and Barr Laboratories Inc. -- after they submitted proposals with the FDA to produce generic versions of modafinil, which is the active ingredient in Provigil.
"We have reviewed each of these filings in detail," said John E. Osborn, senior vice president and general counsel of Cephalon. "We have not found anything in them that is surprising or unanticipated. Our patent was approved by the United States Patent and Trademark Office based on the results of extensive research by Cephalon, and we continue to believe that our patent position for this product is strong."
If the generic drug companies are successful at contesting Cephalon's Provigil patent, the earliest they would be able to enter the market with a generic modafinil product is mid-2006.
Cephalon officials believe they have pharmaceutical composition patents that protect Provigil until 2014.
In the second quarter of this year, sales of Provigil hit $69.5 million, a 40 percent increase over the comparable period last year. Provigil generated total sales of $196.3 million last year.
"Provigil is today our largest product and we believe it will be a successful product for many years," Baldino said.
The company is now developing a new "R-isomer" version of modafinil as well as a proprietary formulation of Provigil for children suffering from attention deficit hyperactivity disorder.
Baldino said Provigil contains two substances known as "R" and "S" isomers. The company discovered modafinil containing just the R-isomer has a longer duration and a better metabolic profile than the original version of Provigil. The longer duration means the drug's dosage can be lower, resulting in fewer side effects, and the improved metabolic profile means it can be better tolerated when used with other pharmaceutical products.
Cephalon expects to have the R-isomer version approved before any generics could hit the market in 2006.
"One way of getting around potential generic competition is to launch ahead of it and get a better product in the market," Baldino said.
Cephalon expects to begin late-stage testing of its ADHD formulation of Provigil, which has already generated encouraging clinical trial results, this fall.
Baldino said while Provigil is now the company's lead product, he has high expectations for Gabitril, a drug Cephalon acquired in 2001 and is now approved as a treatment for epilepsy. Cephalon is testing the drug for a variety of other conditions including anxiety, insomnia and neuropathic pain.
"The timing is such," Baldino said, "that we believe Gabitril will be ramping up into larger markets" in 2006, the earliest time Provigil could face generic competition.
Last month, CollaGenex received a preliminary injunction that temporarily prevents the FDA from approving any abbreviated new drug applications submitted for a generic capsule or tablet dosage form of its gum treatment Periostat.
Under the ruling, the FDA cannot approve any generic version of Periostat until the U.S. District Court of the District of Columbia makes a final ruling on whether Periostat should be classified as an antibiotic.
Brian Gallagher, CollaGenex's president and CEO, said that while his company continues to remain confident in its ability to withstand challenges based on the validity of its patents, the U.S. District Court ruling may provide CollaGenex with an additional opportunity to seek enforcement of its intellectual property.
CollaGenex earlier this year initiated patent infringement litigation against two generic drug manufacturers, Mutual Pharmaceutical Co. and West-ward Pharmaceutical Corp.' that are seeking to introduce generic versions of doxycycline hyclate, the active ingredient in Periostat, into the U.S. market.
In its complaint, CollaGenex said it is the exclusive licensee of patents, assigned to the Research Foundation of State University of New York, that cover, among other things, the use of doxycycline to treat adult periodontitis.
Mutual responded last month by filing a complaint at U.S. District Court in Philadelphia alleging that CollaGenex has engaged in "tortuous and anticompetitive" behavior in an effort to prevent Mutual from commercializing a generic form of Periostat.
Periostat was OK'd by the FDA in 1998 as a treatment for gum disease in adults. The drug works by inhibiting the enzymes found in inflamed gums that damage the gums and the bones which hold teeth in place.
CollaGenex is testing Periostat as a potential treatment for a variety of skin disorders, including acne.
The company also completed its initial phase-I clinical study of a new sustained release, once-daily version of Periostat -- called Periostat SR -- that could help CollaGenex ward off generic competition.
CollaGenex worked with Shire Laboratories Inc. on the development of Periostat SR, which incorporates Shire's proprietary controlled-release delivery technology. CollaGenex has already filed for intellectual property protection for the new formulation of Periostat.
"Patent protection is always a significant area of concern," said Fritz Bittenbender, president of the Pennsylvania Biotechnology Association. "A lot of our early-stage companies are looking for venture capital money and one of the things that attracts venture capital companies is having a strong patent."
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