Regeneron/Sanofi, Amgen PCSK9 Rivalry Continues, But Not In US Courts
Federal Circuit Affirms Invalidation Of Two Amgen Patents
Executive Summary
The battle for PCSK9 inhibitor market share continues with Amgen’s Repatha outselling Praluent, but a now-ended patent dispute no longer threatens Regeneron’s ability to sell its product in the US.
Regeneron Pharmaceuticals, Inc. is the victor in a long-running US patent dispute with Amgen, Inc. over patents pertaining to antibody therapies targeting PCSK9 for the reduction of LDL cholesterol in the treatment of hypercholesterolemia. Regeneron and its partner Sanofi continue the commercial battle for market share, however, with Amgen’s PCSK9 inhibitor Repatha (evolocumab) generating hundreds of millions of dollars more in global sales than their product Praluent (alirocumab).
Regeneron announced on 11 February that the US Court of Appeals for the Federal Circuit upheld a US District Court for the District of Delaware August 2019 decision that invalidated two Amgen patents related to anti-PCSK9 antibodies. The Federal Circuit decision, which agreed with the lower court and with Regeneron that the patents were too broad, means that all five of Amgen’s patent claims relevant to Praluent are invalidated.
Amgen initiated the long-running patent dispute in 2014 and sought an injunction to stop the manufacture, use and sale of Praluent as long as the product – sold in the US by Regeneron and outside the US by Sanofi – infringed its PCSK9 antibody patents. The litigation went through two district court jury trials and moved back and forth between the Delaware court and Federal Circuit before the appellate court finally ruled in Regeneron’s favor.
Regeneron noted that Praluent was developed with its proprietary technology and the Federal Circuit decision validates the company’s stance that Amgen has no claim to Praluent, “helping to provide closure on this matter.”
Amgen told Scrip that it is “disappointed” with the Federal Circuit’s decision, noting that “Amgen believes that patent protection is essential not only for Amgen but also for the entire biotechnology and pharmaceutical industry to make the significant investments required to discover and develop new innovative therapeutics that serve unmet patient needs. Amgen firmly believes in the validity of its patent.”
Patent Battle Lost, Repatha Winning Commercial War
The company may have lost its patent battle, but it has won the commercial war so far. Amgen reported $887m in Repatha sales in 2020, up 34% from $661m in in 2019. Regeneron reported global Praluent sales of $358.8m, which was up 24% from $288.7m in 2019. Sanofi recognized €261m ($316.3m) in Praluent sales in 2020, up 2.3% from the prior year.
While Praluent sales are more than $300m away from blockbuster status, Amgen noted that with $253m in Repatha sales in the fourth quarter of last year the product is now annualizing at more than $1bn in sales.
Even so, it has taken a long time for the PCSK9 inhibitors to get as far as they have, since first-line treatment of high LDL cholesterol begins with now-generic, oral, small molecule statins that are highly effective in many patients. Blockbuster status has eluded both biologics for more than half a decade.
Praluent was approved in the US in 2015 with a wholesale acquisition cost (WAC) of $14,600, which was higher than a $10,000 to $12,000 estimated WAC. (Also see "Sanofi/Regeneron win 1st US PCSK9 OK with Praluent" - Scrip, 24 Jul, 2015.) Repatha was approved a month later in the US and Amgen set a WAC price of $14,100. (Also see "Repatha OK'd; Payers Eye PCSK9 Rebate/Discount War" - Scrip, 28 Aug, 2015.)
Amgen and Regeneron/Sanofi have had to convince doctors to prescribe a biologic with a new mechanism of action, convince patients that they’ll benefit from treatment with a relatively expensive injection, and negotiate steep discounts with payers accustomed to reimbursing the cost of inexpensive pills for hypercholesterolemia.
By October 2018, when Amgen said about 75% of US patients covered by Medicare were abandoning their Repatha prescriptions at the pharmacy counter due to the biologic’s high out-of-pocket cost, the company announced plans to introduce a different version of the product with a 60% lower WAC cost of $5,850. (Also see "Amgen Drops Repatha List Price 60% To Cut Medicare Co-Pays And Boost Use" - Scrip, 24 Oct, 2018.) Five months later, Regeneron and Sanofi said they also would cut Praluent’s list price to $5,850. (Also see "Sanofi/Regeneron Cut Praluent List Price As PBMs Look To Maintain Rebate Status Quo" - Scrip, 12 Feb, 2019.)
Regeneron won US Food and Drug Administration approval of a new biologic approach to reducing high cholesterol on 11 February when the agency cleared Evkeeza (evinacumab) for homozygous familial hypercholesterolemia (HoFH) – a 1,300-patient rare disease population versus the millions of Americans eligible for Praluent treatment because they can’t tolerate statins or their hypercholesterolemia isn’t well controlled by statins.
While Evkeeza, a first-in-class angiopoietin-like 3 (ANGPTL3) inhibitor, is not being positioned as a competitor to Praluent and Repatha, Pfizer Inc. and Ionis Pharmaceuticals, Inc. are developing the ANGPTL3 inhibitor vupanorsen for a broader population of patients with planning under way for an extensive Phase III program, including a cardiovascular outcomes trial (CVOT).
CVOT trial results for Repatha and Praluent were seen as necessary not only to give regulators comfort with the medicines’ use in a large patient population, but also to boost commercial prospects for the Amgen and Regeneron products. (Also see "Can Sanofi Catch Up With Amgen Now That Praluent Has CV Risk-Reduction Claim?" - Scrip, 29 Apr, 2019.)
A near-term competitor to Repatha and Praluent – administered once or twice monthly – was delayed in December when the US FDA issued a complete response letter rejecting Novartis AG’s PCSK9 inhibitor Leqvio (inclisiran), which is given twice-yearly. Novartis CEO Vas Narasimhan said last month that the CRL related to manufacturing questions from the FDA and the company plans to resubmit its Leqvio biologic license application to the agency in the second or third quarter of this year. (Also see "Long Wait Ahead For Novartis's Leqvio In US" - Scrip, 26 Jan, 2021.)
Outside the US, Sanofi said in its fourth quarter earnings statement that Q4 Praluent sales decreased 8% to €65m due to lower US sales that were more than offset by a 44% increase in sales in Europe. Sanofi launched the product in China in April.
Patent litigation between Amgen and Sanofi began in Europe in 2016. Lawsuits have been filed by or against Amgen in the UK, Germany, France, the Netherlands, Italy, Spain and Japan. The European Patent Office Technical Board of Appeal invalidated certain functional claims of Amgen’s European PCSK9 antibody patent in October.
“As a result of the TBA’s decision, national litigations regarding Praluent in Europe are in the process of being resolved,” Amgen said in its annual report filed with the US Securities and Exchange Commission on 9 February.
The Japan Supreme Court ruled in Amgen’s favor in April and damages proceedings against Sanofi are ongoing there, but the French big pharma has initiated new invalidity challenges in Japan, according to Amgen’s annual report.