Event - FDA on parallel track with Europe on Potiga

Analysis

Potiga (ezogabine) may get a judgement in the US before it does in Europe (Event - Valeant’s recent efforts reduce dependence on retigabine, June 10, 2010). An FDA advisory committee will make its recommendation on August 11, yet it is anybody’s guess what the panel will do with the Valeant Pharmaceuticals International adjunctive treatment for partial onset seizures.

Observers believe the FDA’s increasing caution in central nervous system drugs, as well as ezogabine’s high dropout rate from adverse events, will raise some question marks among panellists and FDA staff members assessing the novel potassium channel/GABA agonist. The FDA has already turned back one epilepsy drug so far this year, Dainippon’s Stedesa (Dainippon receives an unwelcome knock back to Stedesa, May 4, 2010).

Product Potiga (retigabine)
Company Valeant Pharmaceuticals International
GlaxoSmithKline
Market cap Valeant $4.37bn
GSK $85.6bn
Product NPV Valeant $193m
GSK $188m
% of market cap Valeant 4%
GSK 0%
Event type FDA advisory committee
Date August 11, 2010

In addition, ezogabine’s pivotal trials were against placebo, rather than marketed drugs, raising questions as to whether it will be a success in an already-crowded and genericised anti-epileptic market. Thus, observers are not overly excited about the prospects for ezogabine, formerly known generically as retigabine.

Although the FDA is still scheduled to deliver its final verdict on Potiga by the drug's PDUFA date of August 30, the chances of a standard three-month postponement seems high.

Urge to merge

As it awaits regulatory rulings on both continents, Valeant is in the midst of its own merger with Canada’s Biovail (Biovail and Valeant join forces to drive growth, June 22, 2010). Shares in both companies have been on an upward trend since the announcement of the $3.2bn merger.

The merger will create both a catalogue of established products and a pipeline of promising candidates – although it is worth noting that in addition to ezogabine only Biovail’s schinzophrenia treatment AZ-004 and Parkinson’s disease treatment JP-1730 have sales estimates attached to them. As such, a win on ezogabine would set an early positive tone for the merger.

According to EvaluatePharma data, ezogabine is projected to have worldwide sales of $219m in 2016 for Valeant’s partner GlaxoSmithKline, earning Valeant $97m in royalties and giving it a net present value of $193m for the California company.

Novel target, ho-hum results

In its favour, ezogabine has a novel target in the potassium channel. By opening the potassium channel, ezogabine dampens neuronal excitability and reduces the risk of seizures. It is being developed for patients with simple or complex partial seizures who are inadequately-controlled on one to three anti-epileptic drugs, and would give physicians another tool to control seizures in refractory patients.

While ezogabine showed statistically significant reduction in the frequency of seizures when compared to placebo, it also had a higher dropout rate from adverse events; in the pivotal Restore I trial, the dropout rate was 27% for patients on 1,200mg a day of ezogabine compared with 8.6% for placebo, and in the Restore II trial the dropout rate was 14.4% for patients on 600mg a day and 25.8% for those on 900mg, compared with 7.8% for placebo. Dizziness, somnolence, fatigue, and nausea were among the adverse events that subjects in the ezogabine arms reported.

Added to the adverse events is the relatively short half-life of ezogabine, which therefore requires it be dosed three times a day, presenting patient compliance challenges.

Meanwhile, the market is becoming heavily genericised. Former top-sellers Topamax, Lamictal, Depakote and Keppra all lost patent protection in 2008, meaning that new drugs must significantly differentiate themselves on efficacy or safety grounds to gain commercial traction. So far, many observers do not seem to believe ezogabine has that ability.

The dim commercial prospects did not stop GSK from licensing the candidate in 2008 for $125m upfront and milestones of up to $545m, plus royalties, along with co-promotion rights in the key US market. How enthusiastic the UK company is about the drug is not clear, and it requires a suprisingly positive regulatory clearance in the US and Europe for GSK to see any return on this investment.

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