Xenoport Gets Aftershock on Gabapentin Enacarbil

Home , Calcium channel blocker, Gabapentin enacarbil

July 08, 2010 XenoPort gets aftershock on gabapentin enacarbil

Jonathan Gardner

XenoPort’s second major clinical setback of 2010 has them in a tight spot. A phase IIb trial of gabapentin enacarbil in migraine prophylaxis did not show statistically significant improvement in the number of days with a migraine from baseline over 30 weeks in a dose ranging study, driving shares in the California company down 27% in Wednesday trading.

Coming as it does five months after receiving a complete response letter for the drug after it was submitted as Horizant in moderate to severe restless legs syndrome (RLS) (XenoPort reels from Horizant rebuff, suspends pain research, February 18, 2010), the new trial results are another blow for the transported prodrug of the commonly used epilepsy treatment. Given that the FDA’s response to the RLS submission was related to a safety signal on the development of pancreatic acinar cell tumours in rats, this newest disappointment could spell the beginning of the end for this formulation of gabapentin enacarbil.

Placebo response, CNS outlook

In announcing the failure of the phase IIb trial, executives from XenoPort and partner GlaxoSmithKline said the results may have been harmed by a greater than anticipated placebo response, a frequent claim following failed clinical studies in pain indications. With GSK walking away from CNS indications (Glaxo announces cull that could get partners squirming, February 4, 2010), it seems likely that GSK will not want to press forward with gabapentin enacarbil, and XenoPort will soon beat the same retreat.

XenoPort licensed the calcium channel blocker to GSK in 2007 worldwide, excluding some Asian countries, in a deal worth up to $641m and US co-promotion rights. Astellas Pharma has rights in Japan - where it is still considered a candidate for RLS – as well as Korea, the Phillippines, Indonesia, Thailand and Taiwan for an upfront fee of $25m and $60m in milestones.

The RLS complete response letter was a far bigger blow for XenoPort than the migraine setback, wiping two- thirds of its market value off the books in a single day – the shares dropped from $19.60 to $6.67. XenoPort had recovered some of these losses – closing as high as $11.46 on May 13 – but the phase IIb results sank the shares below their post-RLS lows, with a Wednesday close of $6.51. Shares were at $6.50 in early trading Thursday.

Dwindling cash

After Wednesday’s shock, XenoPort’s market capitalisation stands at $198m, still above cash levels at March 31 of $123m, but not by much. The company announced March 5 it was halving its workforce, a move that reduced the company’s annual cash outlay by $15.6m but incurred a $4.2m charge. With projected cash burn of $67m in 2010, $62m in 2011 and $50m in 2012 before the cut backs were announced, the workforce reduction probably leaves XenoPort with around two-and-a-half years of funding.

This is a bit of a turnaround for XenoPort’s funding picture. According to archived consensus forecasts from EvaluatePharma, as recently as December 2009 analysts were forecasting that GSK would book $93m in sales in 2010 and $116m in 2011, from which XenoPort would have collected decent royalties and co-promotion revenue.

XenoPort’s strategy has been to alter the chemical makeup of existing off-patent drugs to improve their gastrointestinal absorption. It identifies high-capacity nutrient transporter proteins in the GI tract to promote active transport and improve bioavailability.

It has two other drugs in clinical development, both of which are altered generics: XP19986, an R-isomer of the GERD drug baclofen, in phase IIb trials in patients who remain symptomatic despite use of a proton-pump inhibitor, and XP21279, an altered version of levodopa, for Parkinson’s disease, on which it would like to initiate phase II trials. Both of those drugs remain unpartnered, which of course means that all R&D costs are on the company. The current phase IIb study on XP19986 is scheduled to conclude in December 2010, according to clinicaltrials.gov. Assuming the results are positive and that the company has been unable to partner the drug prior to the results, XenoPort will have just over a year to partner the drug before the cash runs out. They will not exactly be bargaining from a position of strength.