PCSK9 wrangle opens can of worms for antibody makers

Regeneron and Sanofi's PCSK9 court win could reverberate across the whole monoclonal antibody space.

Last week’s US court victory for Regeneron and Sanofi could help the companies’ PCSK9 antibody Praluent catch up with Amgen’s rival product Repatha, reversing gains made by the latter since January’s injunction.

But the case could also have implications for the rest of the industry by dealing a blow to the so-called “antibody exception” rule – if this falls by the wayside, competition in the antibody space is expected to heat up. The picture should become clearer with the re-trial of the case, which is likely to take place next year.

Ultimately, success for Amgen could make it more important for antibody developers to be first to market for intellectual property purposes; if Regeneron and Sanofi prevail, existing antibody IP could become vulnerable, Mizuho analysts noted.

No exceptions?

Much of the outcome hinges on how the court views the “antibody exception” doctrine, which has allowed patents based solely on a description of the target antigen, rather than the antibody itself – something that Amgen relied on heavily for Repatha’s composition of matter patent.

Previous decisions by the US Court of Appeals have hinted at eliminating antibody exception, but this was the first time the court said it “had no justification in law, and that the rules for antibodies should be no different than the rules for small molecule”, Leerink analysts wrote.

This decision plays into Regeneron’s hands: the company has long argued that Amgen’s patents for Repatha are invalid, citing an insufficient written description for its broad claim for any antibody that binds to specific residues on the PCSK9 antigen.

However, Regeneron was not allowed to present evidence supporting this stance in the original trial in January, which resulted in an injunction against Praluent (Amgen in position to dictate terms in PCSK9 tussle, January 6, 2017). 

The court of appeals has now ruled that this was an error, dismissing the injunction and setting up a new court battle, during which Repatha’s composition of matter patents could be invalidated.

As well as being a blow to Amgen, this would have a knock-on effect on existing, similar broad antibody patents – and maybe also royalties on these – as well as raising standards for new antibody patents. 

It could also potentially hasten the entry of biosimilars, if it makes it harder for the originator to defend a broad portfolio of patents.

But, even if this does happen, it will be a while before any changes filter through. For now, Regeneron and Sanofi will be celebrating a decision that at least gives Praluent a chance to regain ground from its arch rival.

Thanks to a stay against the injunction, the companies had been able to keep selling their PCSK9 inhibitor, but Praluent had already begun to fall behind Repatha (Praluent stay not enough to save Regeneron, February 9, 2017). 

Expectations for both drugs have been on the slide, but the fall in EvaluatePharma sellside consensus for Praluent in the past year has been more dramatic.

The changing fortunes of the PCSK9 inhibitors
2022e sales ($bn)
Product Current forecast Forecast in Oct 2016 Change ($m)
Repatha 3.19 4.14 -950
Praluent 1.60 3.06 -1,460
Source: EvaluatePharma.

The Leerink analysts estimate that, in light of the latest decision, Praluent could now bring in $2.5bn in 2022, giving it a 42% share of the PCSK9 inhibitor market.

Of course, this will also depend on data from Praluent’s cardiovascular outcomes trial, Odyssey Outcomes, due in the first quarter of 2018. If this betters the 15% reduction in cardiovascular events seen with Repatha in the Fourier trial, Regeneron and Sanofi will be back in the game.

But the latest court decision means that, even if it produces a similar result, Praluent cannot be written off just yet.

Study Trial ID
Odyssey Outcomes NCT01663402

To contact the writer of this story email Madeleine Armstrong in London at madeleinea@epvantage.com or follow @ByMadeleineA on Twitter

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