While XenoPort’s phase II trial readout for XP23829 concerns psoriasis, it is not these data that are exciting investors and analysts but the read-across that a positive result would have in multiple sclerosis.
XP23829 is a prodrug of monomethyl fumarate, the active metabolite of Biogen’s MS blockbuster Tecfidera. If XP23829 can show Tecfidera-like activity in a similar auto-immune disease, XenoPort could quickly develop the drug for MS and capture a share of the lucrative market that Tecfidera enjoys.
Furthermore, XP23829 has different pharmacokinetics to Tecfidera, and its proifile suggests it has a lower propensity for skin and GI irritation side-effects. This could allow it to be given in a larger dose once-daily, versus twice-daily for the Biogen drug.
Calculating the odds
Analysts at RBC speculate that the results could catalyse a 20-50% stock price movement in either direction, depending on how the data are interpreted. They describe three different possible scenarios: the study shows statistically significant results with efficacy that is better than Tecfidera with a safety/tolerability advantage; the study shows significant results with efficacy/safety that is similar to Tecfidera; and the study shows efficacy lower than Tecfidera with no differentiation on safety/tolerability. To the first scenario it ascribes a 15-20% probability, the second, 50% and the third, 30-35%.
It is therefore fair to say that the data will be very closely examined.
XenoPort’s 200-patient study tests three different doses of XP23829: 400mg once daily, 400mg twice daily – which is thought to deliver the same exposure to MMF as Tecfidera – and 800mg once daily. They are also being compared with placebo, in patients with moderate-to-severe chronic plaque-type psoriasis.
The primary endpoint is reduction in the psoriasis area and severity index score (PASI) at 12 weeks versus baseline. Secondary endpoints are the proportion of subjects who achieve a 75% or greater reduction in PASI from baseline (PASI-75) and the proportion of proportion of subjects who achieve a static Physician's Global Assessment (sPGA) score of clear or almost clear.
The real comparison is of course the efficacy seen in a phase III study of Tecfidera, also in moderate to severe psoriasis, which Biogen reported in 2005. This study showed a reduction of around 50% in PASI at 8 weeks and around 70% at 16 weeks. If XP23829 shows a PASI reduction in the 45-55% range at 12 weeks, it would be deemed comparable to Tecfidera, at least from the investor’s point of view.
Ostensibly, if the study is succesful, XenoPort intends to conduct a phase III study for psoriasis, but the investment community will be looking to see how it can tackle the larger MS opportunity.
XenoPort believes it can move directly into pivotal phase III trials, and it already has agreement with the FDA on the key aspects of its proposed clinical development programme in MS including that an NDA could be based on a single trial.
The stakes are high. Tecfidera is the top-selling MS product and continuing to grow fast. EvaluatePharma consensus data suggest it will achieve sales of $4bn this year, rising to more than $6bn by 2020.
With so much to play for it is no wonder XenoPort is in a hurry to move into MS.