Sensipar Generics: US Court Victory, FDA Approval Position Piramal For Launch

Just days after Piramal was one of three generic drug sponsors found not to have infringed a Sensipar formulation patent, FDA approved company’s ANDA, threatening Amgen’s de facto exclusivity on the blockbuster calcium-sensing receptor agonist.

Launch of the first US generic of Amgen Inc.’s hyperparathyroidism treatment Sensipar (cinacalcet) moved two steps closer to reality with a federal judge’s patent noninfringement ruling for Piramal Healthcare UK Ltd., followed just days later by FDA approval of the company’s abbreviated new drug application (ANDA).

The two events position Piramal as the only cincalcet ANDA sponsor with full approval and a court ruling of noninfringement on Amgen’s formulation patent (No. 9,375,405), which expires in September 2026.

Amgen has been able to protect Sensipar from generic competition for at least five months after its drug substance patent expired in March despite FDA's denial of six-month pediatric exclusivity.

Legally, it appears Piramal could launch and get a jump on a host of other ANDA sponsors seeking a piece of the US market for the blockbuster calcium-sensing receptor agonist. Amgen reported US Sensipar sales of $739m in the first half of 2018.

Amgen has been able to protect Sensipar from generic competition for at least five months after its drug substance patent (No. 6,011,068) expired in March even though FDA denied the innovator a six-month pediatric extension – a regulatory decision that remains the subject of litigation.

Piramal told the Pink Sheet that launch plans and timing will be decided in consultation with its US marketing partner, which it did not identify.

Three Sponsors Prevail At Infringement Trial …

Amgen has sued a host of generic companies for infringement of the ‘405 patent, although many of the cases have settled.

In early March, Judge Mitchell Goldberg of the US District Court for the District of Delaware presided over a four-day bench trial between Amgen and a several ANDA sponsors limited to infringement claims, with defendants’ counterclaims for patent invalidity to be tried at a later date if necessary. (Also see "US Launch Of Sensipar Generics May Await Patent Case Even After FDA Approval" - Pink Sheet, 14 Mar, 2018.)

Four ANDA sponsors and their affiliates were the focus of Judge Goldberg’s July 26 memorandum: Amneal Pharmaceuticals LLC; Piramal; Watson Laboratories Inc.; and Zydus Pharmaceuticals (USA) Inc.

Of the four defendants, only Zydus held full approval at the time of Judge Goldberg’s decision, having been approved April 23. Three other ANDA sponsors – Aurobindo Pharma Ltd., Cipla Ltd. and Strides Pharma Inc. – hold ANDA full approval but have settled with Amgen.

At issue in the patent infringement trial was whether the four defendants’ ANDAs infringed the ‘405 patent’s claims related to the amount of specific excipients combined with cinacalcet hydrochloride.

In his July 26 opinion, Judge Goldberg ruled that the cincalcet ANDAs from Piaramal, Amneal and Watson do not infringe the ‘405 patent either literally or under the doctrine of equivalents.

However, the court concluded that Zydus’ ANDA infringes claim 1 of the ‘405 patent and several dependent claims “to the extent the claims are valid and enforceable.”

Judge Goldberg requested the parties schedule an in-person status conference and submit a joint letter setting forth their proposals for how the court should proceed with respect to the invalidity trial and pending motions filed by Amneal and Zydus.

… One Prevails At FDA

The court’s decision had no immediate impact because the only ANDA sponsor found to have infringed was also the only sponsor with full approval.

However, that all changed Aug. 1 when FDA approved Piramal’s ANDA for cincalcet tablets in 30 mg, 60 mg, and 90 mg doses.

“We are pleased with the US district court ruling in favour of our position on Sensipar. It confirms our non-infringing IP position, and validates our strategy,” Ramesh Subramanian, senior vice president of strategic marketing at Piramal Pharma Solutions, told the Pink Sheet. “We are also excited to have recently received the final ANDA approval – a testament to the hard work the Piramal team had put on the cinacalcet ANDA.”

“Any potential launch by one of the companies that the district court found not to infringe would be at risk.” – Amgen

In a statement to the Pink Sheet, Amgen said that final judgment has not been entered with respect to any of the parties subject to the district court’s decision on patent infringement.

“Amgen will be seeking an appeal of the noninfringement decision,” the company said. “Any potential launch by one of the companies that the district court found not to infringe would be at risk.”

Pediatric Exclusivity Dispute Pending

While the timing of generic market entry remains uncertain, Piramal said the pending federal appeals court decision on pediatric exclusivity for Sensipar “has no impact on our launch plans.”

The US Court of Appeals for the District of Columbia Circuit heard oral arguments May 17 on Amgen’s challenge to an FDA decision denying a six-month pediatric exclusivity extension for the ‘068 drug substance patent, which expired March 8. (Also see "Amgen’s Challenge Over Sensipar Pediatric Exclusivity Moves To US Appeals Court" - Pink Sheet, 17 May, 2018.)

Amgen is contesting the agency’s conclusion that its pediatric studies did not “fairly respond” to an FDA written request because only three of the four study requirements were satisfied.

The appeals court has not yet handed down its decision in the exclusivity dispute. However, even if it comes soon it and is favorable to Amgen, its impact on Sensipar is likely to be limited.

If awarded from the day of patent expiry, the six-month extension would run through Sept. 8. Thus, even though FDA declined to award Amgen statutory exclusivity on the ‘068 patent, litigation over the ‘405 patent has bought Amgen at least five months of de facto exclusivity, although that protection may be nearing an end.

Anju Ghangurde contributed to this report.