XenoPort sees little hope beyond the Horizant


The failure in phase III and subsequent abandonment of arbaclofen placarbil by its developer, XenoPort, has precipitated a 15% drop in share price and wiped $49m off the company’s market cap.

If this weren’t enough, the loss of the MS spasticity drug removes any shred of hope that XenoPort will achieve profitability within the next decade – the firm’s one marketed drug, Horizant, will bring in just $9m this year and $36m in 2018, according to EvaluatePharma. Intriguingly, though, XenoPort is still trading comfortably above cash. Investors must think that the company’s most-advanced remaining candidate, a Parkinson's disease therapy in phase II, has an extraordinary future.

Déjà vu

XenoPort did not release a great deal of detail about the trial beyond saying that arbaclofen failed to provide a statistically significant improvement relative to placebo in the co-primary endpoints of the study. These were change from baseline in the patients’ maximum score on the Ashworth scale, which measures spasticity, and patients’ assessments of pain reduction.

The results must have given the company a nasty case of déjà vu. Arbaclofen had already failed so badly in gastro-oesophageal reflux disease that the company had to ditch it in phase II (XenoPort GERD data disappoints, December 3, 2008).

Arbaclofen placarbil is a sustained-release prodrug of the generic muscle relaxant baclofen. To have stood a chance in the market arbaclofen would have had to demonstrate not just equivalence with, but superiority to, generic baclofen (Event – XenoPort gets a second shot on goal with arbaclofen, January 15, 2013). A miss when compared with placebo meant it did not even get to that stage. This is a grave disappointment, and casts doubt on the company’s platform.

And both of XenoPort’s surviving clinical-phase products have been developed using the same approach. XP21279, in phase II trials for Parkinson’s disease, is a prodrug of levodopa; XP23829 is a precursor to monomethyl fumarate (MMF) intended as a therapy for MS.

Tecfidera II

The company is talking up its MS candidate in particular, and this is because there is already a MMF prodrug on the market for MS: Biogen Idec’s Tecfidera, the unstoppable hit of 2013. XenoPort’s CEO Ronald Barrett said on a conference call yesterday that current trials of this product are aimed at building confidence that ‘829 “is a prodrug of MMF in the same way the dimethyl fumarate [Tecfidera] is”.

The company hopes to include a Tecfidera arm in a future multiple ascending dose trial of ‘829 in order to compare the drugs’ pharmacokinetics. If XenoPort can demonstrate pharmacokinetic bioequivalence with Tecfidera, ‘829’s path to US approval will be quicker and cheaper, according to analysts at Leerink Swann.

Perhaps this explains XenoPort’s above-cash value: investors are placing a very high-risk bet that ‘829 will be as successful as Tecfidera. Horizant sales have been disappointing, and arbaclofen is a failure twice over. The California group is due some good fortune, and maybe ‘829 will bring it. The question is whether XenoPort can hang on till that good news arrives – if arrive it does.

Trial  Trial ID
Phase III trial of arbaclofen placarbil in spasticity due to MS  NCT01359566 

To contact the writer of this story email Elizabeth Cairns in London at elizabethc@epvantage.com or follow @LizEPVantage on Twitter

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