Spotlight falls on Orexigen as Vivus jumps through FDA hoop

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After regulatory delays, a retrospective data analysis and a filing resubmission, not even a last-minute media relations snafu that caused chaos in trading yesterday could prevent Vivus’s combination pill from becoming the second obesity drug to secure US approval in under a month.

Like Arena Pharmaceuticals’ lorcaserin, to be sold as Belviq, Vivus’s drug has been given a new brand name – Qsymia, as opposed to the earlier Qnexa. Unlike Belviq, Qsymia comes with a risk-mitigation plan that will limit its market and is as yet unpartnered – something that could become important as Vivus contemplates the scope of post-marketing studies. Perhaps most interesting now will be the performance of the outsider in this three-horse race, Orexigen Therapeutics.

Qsymia has been approved for use in the same range of obese patients as Belviq, but cannot be prescribed in pregnant women because of the teratogenicity risk associated with its topiramate component. Qsymia and Belviq patients alike will have to discontinue if they fail to lose 5% of their weight within 12 weeks’ of treatment (Arena fends off the big question as lorcaserin delivers, June 28, 2012).

While Arena investors breathed sighs of relief that Belviq was approved without the need for a risk-mitigation programme, Vivus will have to put one in place to inform doctors about the risks of prescribing Qsymia to women with childbearing potential.

A question of efficacy

Restrictions aside, Qsymia is clearly more efficacious than Belviq, although whether this translates into higher revenues remains to be seen (see table below).

Perhaps this is where Orexigen comes in. Its own combination therapy Contrave, licensed to Takeda, was like Belviq and Qsymia rejected by the FDA at the first pass. Orexigen then had to begin a cardiovascular outcomes trial while Arena and Vivus were allowed to run theirs after launch.

The Contrave study, in almost 10,000 patients, is subject to an all-important interim analysis once at least 87 major adverse events have occurred, expected next year. Assuming that this analysis works in Contrave’s favour a resubmission to the FDA could be made shortly afterwards, with a regulatory decision in 2014.

True, this puts Contrave well behind Qsymia and Belviq, which will be launched over the next four to six months while Vivus completes manufacturing and trains a sales force and Arena finalises drug enforcement scheduling. But there is clearly room for three products in this market, and Vivus’s CEO, Leland Wilson, said on a call that he “fully expects the third [obesity drug] to be approved”.

Drug  Study Placebo-adjusted weight loss Patients losing ≥5% of body weight vs placebo
Qsymia Equate 7.5% 66% vs 15%
Qsymia Equip 9.4% 67% vs 17%
Qsymia Conquer 8.6% 70% vs 21%
Contrave NB-301 4.8% 48% vs 16%
Contrave NB-302 4.2% 66% vs 43%
Contrave NB-303 5.2% 56% vs 17%
Contrave NB-304 3.2% 45% vs 19%
Belviq Bloom 3.6% 48% vs 20%
Belviq Blossom 3.1% 47% vs 25%

Day of chaos

Vivus suffered a day of chaos yesterday after what looked like a PR disaster over an embargoed story led to USA Today reporting news of Qsymia’s approval hours before actual word of the all-clear came from the FDA. After a particularly volatile day’s trading, the markets currently value Vivus at $2.6bn and Arena at $1.9bn.

A remaining uncertainty for Vivus is the fact Qsymia is unpartnered. While a deal on an approved drug might secure highly advantageous terms and a hefty upfront payment, a licensee might be put off by a likely need to finance the cardiovascular trial, whose size and scope has yet to be determined. News on that should come in the third quarter, after discussions with the FDA.

It is also not known whether big pharma is interested in the obesity area, which it effectively abandoned five years ago, or Qsymia, a fixed-dose combination of two off-patent molecules. At their current market caps Arena and Vivus certainly have far to fall should their drugs not live up to the hype, and investors are no doubt braced for continued volatility beyond market launch.

With the first two entrants set to test the market, some might think that Orexigen – capitalised at just $468m - could offer a more interesting risk-reward balance.

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