Event – Gilenia’s safety the main focus of advisory committee

The stop, start nature of the race to bring the first oral drug for MS to the market reaches another critical point this week when an FDA advisory committee will review the efficacy and safety profile of Novartis’ Gilenia (fingolimod; FTY720) on June 10, with the relevant briefing documents likely to be published tomorrow afternoon.

While the experts convened by the FDA are expected to agree the efficacy of Gilenia is sufficient with data showing significant reductions in relapse rates against placebo and standard of care treatment beta interferon, the drug’s safety profile is likely to draw severe scrutiny and doubtless some concern. A positive vote on Gilenia’s safety, or at least an acceptance of risk with agreement on a manageable REMS program, would be a major boost for a drug that many analysts believe remains undervalued by the market, despite blockbuster sales forecasts and an estimated worth of $2.35bn to Novartis.

Product Gilenia Gilenia
Company Novartis Mitsubishi Tanabe Pharma
Market Cap $99.5bn $7.95bn
Product NPV $2.35bn $204m (based on royalties)
% of Market Cap 2% 3%
Event type FDA advisory committee FDA advisory committee
Date 10 June 2010 10 June 2010
Could Impact Movectro (Merck KGaA)

Safety, safety, safety

Although more recently published and longer-term clinical trial data on Gilenia appear to suggest a slightly more benign side effect profile for the drug (New data heats up race for new oral MS therapy, January 21, 2010), the problem is that safety concerns have consistently dogged Gilenia’s clinical development, an image that will be hard to shrug off.

The safety concerns include evidence of: a higher rate of melanoma, respiratory tract and herpes infections including two deaths from herpes infections, and cardiovascular irregularities such as reduced heart rate and slight increase in blood pressure which may require monitoring.

Those with a more bullish outlook on Gilenia point to the fact the bulk of these side effects were seen at the highest dose, 1.25mg, and not at the much lower filed dose of 0.5mg. The lower dose managed to maintain the same efficacy level as the high dose, yet herein lies another potential stumbling block as there is some concern the experts may question whether Novartis has really tested the full dosing range of the drug in phase II trials.

The threat here is that either the panel or the FDA requests further trials at lower doses to determine if the same efficacy can be achieved with greater safety. The FDA recently delayed Gilenia’s PDUFA review date by three months and a decision is therefore expected by September 21.

Clear blockbuster potential

Latest consensus forecasts from EvaluatePharma project Gilenia sales of $952m by 2016, although that figure could rise significantly should the advisory committee rule in favour of the drug and raise expectations for final approval by September.

Nomura, for example, has pencilled in sales of $2.1bn by 2014, three times the current consensus of $674m in that year.

Gilenia is Novartis’ second most valuable pipeline candidate, behind MenB vaccine which is currently valued at $4.41bn, so significant upgrades of Nomura proportions could yet make Gilenia its most valuable and one of the Swiss group’s biggest new product launches in recent years.

Not homegrown

Although Novartis has been fully responsible for Gilenia’s clinical and regulatory development, the drug is not actually a discovery from its own laboratories. The Swiss healthcare giant licensed worldwide rights to the drug in 1997, when pre-clinical studies were still ongoing, from Yoshitomi Pharmaceutical, one of a number of forerunner companies which make up Mitsubishi Tanabe Pharma as it is today.

As such Mitsubishi Tanabe, who will receive modest royalties on Gilenia’s sales, stands to benefit from the regulatory and commercial success of the drug. Even with projected royalties of just $60m by 2016, Gilenia is by far its most valuable pipeline candidate; shares in the Japanese group gained 9% last week to ¥1,285 which some analysts were attributing to the upcoming advisory committee review.

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