GlaxoSmithKline/XenoPort: generic competition and safety warnings cast mist over Horizant's horizons

Horizant's approval by the FDA offers patients with postherpetic neuralgia an improved dosing regimen over available treatment options. However, Horizant will face fierce competition in the US from generic gabapentin and the once-daily gabapentin formulation Gralise (Depomed). Moreover, safety warnings surrounding significant driving impairment are likely to serve as a deterrent to prescribing.

On June 7, 2012, the FDA approved XenoPort's Horizant (gabapentin enacarbil) for the management of postherpetic neuralgia (PHN) in adults, 10 months after GlaxoSmithKline's submission of a supplemental New Drug Application. The approval represents Horizant's first indication expansion beyond its original label of restless leg syndrome (RLS), for which it gained FDA approval in April 2011. Horizant is to be marketed in the US by GlaxoSmithKline.

The approved dosing regimen of Horizant in the management of PHN is 600mg dosed twice daily. This dosing schedule represents an improvement over available gabapentin products that have historically been dosed up to four times daily, as well as Lyrica (pregabalin; Pfizer), which is dosed three times daily. However, this clinical benefit is overshadowed by the prior entry into the market of the once-daily Gralise (extended-release gabapentin; Depomed), which received approval from the FDA in January 2011 for PHN.

Furthermore, Horizant will face fierce competition from generic versions of gabapentin that have been available in the US since the 2004 expiration of Neurontin's (gabapentin; Pfizer) patent. This will create additional challenges in securing reimbursement from payers.

In common with other gabapentin-based products, the side-effect profile of Horizant includes somnolence and dizziness. However, Horizant's uptake in PHN is likely to be hampered by a warning of significant driving impairment associated with Horizant's use. According to the product's prescribing information, patients are advised that they should not drive until they have had sufficient experience with Horizant to judge whether their driving ability will be impaired. Datamonitor believes that this side effect will raise significant safety concerns with physicians and patients alike.

Datamonitor expects Horizant to achieve modest sales of $157m in the US by 2020. However, the sales of Horizant will not surpass Gralise's peak sales of $256m, which are predicted to be achieved in the US in 2016. Datamonitor is unaware of further expansion beyond the indication of RLS for Horizant in Japan, therefore the EU remains a potential marketing opportunity for XenoPort. However, to achieve growth in the EU, XenoPort will need to secure a commercialization partner with strong sales and marketing presence in the region.