Upcoming events – a legal verdict for Enbrel and a clinical one for Cymabay

Amgen awaits a make-or-break US verdict on its best-selling drug, while Cymabay looks for evidence that it could become a Nash contender.

Welcome to your weekly digest of approaching regulatory and clinical readouts. It is scarcely believable that 21 years after its launch Amgen’s rheumatoid arthritis drug Enbrel is still going strong. And if a US court ruling against a Sandoz biosimilar goes Amgen’s way it might continue going strong for another decade.

2029 is when Amgen says Enbrel’s US patent expires, and this claim is being challenged by Sandoz, whose product Erelzi was approved by the US FDA three years ago but has not yet been launched. A simple yes or no verdict is expected to be handed down imminently.

As ever in US litigation, a simple decision is unlikely to have a simple outcome. A Sandoz victory would not necessarily imply immediate Erelzi launch since Amgen would likely appeal; then there is the likelihood that Amgen would want to settle, something that analysts speculate the parties have already been discussing for months.

This is where a separate but possibly related dispute between Amgen and Sandoz’s parent company, Novartis, comes into play. Last week Amgen told Novartis that it wanted to terminate a collaboration focusing on the migraine drug Aimovig, alleging a material breach.

That breach was Sandoz’s signing of a separate 2015 deal to manufacture Alder’s Aimovig competitor eptinezumab. Novartis claims that it was unaware that Sandoz had struck this deal, and is seeking to terminate the Alder deal – though not soon enough for Amgen.

Evercore ISI analysts speculate that Amgen might not have moved to terminate until now because its deal also included rights to Novartis’s phase III Alzheimer’s project CNP520, which looks worthless after the recent failure of Biogen’s aducanumab, which similarly targets amyloid.

Why is all this relevant to Enbrel? Simply put, by making its allegation Amgen could be twisting Novartis’s arm over an eventual Enbrel settlement. Whether this is even necessary will not be clear until the US verdict is delivered, but with Enbrel accounting for 21% of Amgen’s 2018 revenues there is no harm in attacking early.

Amgen's sales of Enbrel ($m)
2018
2019e
2020e
2021e
2022e
2023e
2024e
5,014
4,620
4,272
3,844
3,479
3,060
2,790
Source: EvaluatePharma consensus forecasts. Note: biosimilars entered the EU in 2016.

Better than Genfit?

Meanwhile, expected mid-stage data from Cymabay's PPAR agonist seladelpar are not as momentous as some of this weekend’s Easl presentations, but the company is firmly in on 2019's Nash party.

Seladelpar is also being tracked by followers of Genfit, whose similarly acting elafibranor faces make-or-break readout of the pivotal Resolve-It trial by the end of 2019. Elafibranor has already failed in phase II, and Cymabay has made much of the claim that it has the best-in-class PPAR agonist.

Cymabay investors’ immediate focus is on a phase II study in which 10mg, 20mg and 50mg seladelpar doses are being compared against placebo in 181 Nash subjects. In the current quarter topline data are expected concerning 12-week change from baseline in liver fat by MRI-PDFF, one of several co-primary endpoints.

Cymabay reckons a 30% reduction in fat is associated with histological Nash improvement, and says such a result would suggest a competitive profile.

A strong showing would bode well for full 52-week results concerning fibrosis and Nash activity score, due in the first half of next year; those, in turn, will determine whether a phase III trial begins in Nash – a far bigger indication than primary biliary cholangitis (PBC), in which a pivotal study is already under way.

Analysts believe that seladelpar could have better efficacy than Intercept's approved Ocaliva, based on mid-stage PBC data.

Though PPAR agonism has caused toxicity concerns for the glitazone class of diabetes drugs, such worries are now thought to concern the gamma receptor subtype. Cymabay argues that seladelpar is highly selective for PPAR delta; Genfit’s elafibranor, meanwhile, is an agonist at PPAR alpha and delta.

Inventiva’s pan-PPAR agonist lanifibranor recently failed in systemic sclerosis. However, Intercept recently licensed Aralez’s broad-acting agonist bezafibrate, showing continuing interest in this mechanism. There is still plenty for Cymabay to play for. 

Cymabay's upcoming seladelpar results
Study Use Data
Phase II (NCT03551522) Nash Q2 2019 (12wk MRI-PDFF)
    H1 2020 (52wk fibrosis & NAS score)
Phase III, Enhance (NCT03602560) Primary biliary cholangitis Dec 2020

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