Angiomax Generics Imminent After Court Rules Patents Are Invalid
This article was originally published in The Pink Sheet Daily
Executive Summary
Exactly when The Medicine Co.'s top seller will see competition isn't clear – highlighting industry concerns with FDA review times for ANDAs. Hospira and Sagent have tentative approval and several other firms have pending applications.
The Medicines Co. could face generic competition for its anticoagulant Angiomax (bivalirudin) four years earlier than expected now that the U.S. Court of Appeals for the Federal Circuit has ruled two patents covering the drug are invalid.
Last year, a district court found that Hospira Inc. failed to prove that claims in the patents were invalid but it said that TMC had not proven that Hospira infringed them (Also see "Angiomax Generic From Hospira Might Launch At-Risk Launch In 2015" - Pink Sheet, 1 Apr, 2014.).
In a July 2 opinion, the Federal Circuit reversed the district court’s ruling on validity as it found that the claims in patent Nos. 7,582,727 and 7,598,343 are invalid under the on-sale bar provision of patent law, which holds that an invention cannot be patented if it has been for sale for more than one year prior to the patent filing and was ready for patenting.
Company CEO Clive Meanwell said in a release that the company is evaluating the ruling and considering its next steps. TMC could seek a review of the decision by the full court.
“We remain committed to interventional cardiovascular medicine and will continue to support bivalirudin,” Meanwell stated. The company has been preparing for its post-Angiomax existence for a while, though (Also see "The Medicines Co. Sets The (Commercial) Stage For New Launches" - Pink Sheet, 5 May, 2015.).
TMC’s composition of matter patent, No. 5,196,404, expired in June. The patents before the Federal Circuit cover pharmaceutical formulations of bivalirudin and processes for making the pharmaceutical batches or formulations. They are set to expire in July 2029 and then would have an additional six-month period of pediatric exclusivity.
Hospira and Sagent Pharmaceuticals Inc. have tentative approvals, according to FDA, but when they would launch remains unclear. Hospira had been contemplating an at-risk launch, but unless the firms had been stockpiling product, both would have to ramp up production.
When other firms could enter the market is even less clear, especially since no others appear to have been approved. While that's good news for Hospira and Sagent, the lost launch opportunity will probably be a reminder to other generic firms just what a critical impact FDA review times can have on their business.
Teva Pharmaceutical Industries Ltd. and Fresenius Kabi AG had settled patent infringement suits with TMC under terms that allowed them to begin selling their generic versions of Angiomax in 2019 or earlier under certain conditions, which would presumably include the launch of other generics. Teva confirmed that it has an ANDA pending at FDA.
TMC has also sued Mylan NV, Dr. Reddy's Laboratories Ltd., Sun Pharmaceutical Industries Ltd. and Apotex Inc.
Specialty pharma company Eagle Pharmaceuticals Inc. submitted a 505(b)(2) NDA for a ready-to-use formulation of bivalirudin that requires neither reconstitution nor initial dilution. It has a user fee review deadline of March 2016 (Also see "Keeping Track: Bristol Has HCV ‘Breakthrough’ Again, Invega Trinza Approved" - Pink Sheet, 25 May, 2015.).
Analysts at Cantor Fitzgerald said in a note that they assume Eagle will be able to generate $9 million in revenue in 2016 based on capturing 10% market share in 60% of the year, at a 75% discount.
Angiomax is TMC’s top-selling drug with worldwide sales of $635.7 million in 2014, including $599.5 million in the U.S.
Batch Production Undermines Patent
The Federal Circuit’s invalidity finding under on-bar sale was based on Ben Venue Laboratories Inc.’s preparation of batches of bivalirudin using the patented method. The district court concluded that no commercial sale occurred because Ben Venue only sold manufacturing services, not pharmaceutical batches, and the batches fall under the experimental use exception.
But the Federal Circuit said the sale of manufacturing services provided a commercial benefit to the inventor more than one year before a patent application was filed and constituted a commercial sale.
“Ben Venue’s services were performed to prove to the FDA that The Medicines Company’s product met the already-approved specifications for finished bivalirudin product,” the ruling states. “Additionally, Ben Venue marked the batches with commercial product codes and customer lot numbers and sent them to The Medicines Company for commercial and clinical packaging, consistent with the commercial sale of pharmaceutical drugs.”
“This commercial activity was not insignificant; The Medicines Company admits that each batch had a commercial value of over $10 million,” the opinion says.