Without delay, FDA sends Lorqess back for more work

In the end the FDA’s rejection of Arena Pharmaceuticals’ Lorqess weight-loss drug was more damning than predicted. In addition to citing cancer signals debated in a negative advisory committee meeting last month, the announcement of the complete response letter also reveals that the agency questioned whether the drug works at all in non-diabetics (Arena falls through floor with adcom vote, September 17, 2010).

It goes without saying the product known generically as lorcaserin is in a battle for its life. News that the FDA has requested data from the Bloom-DM study in type 2 diabetics, due within weeks, suggests that Lorqess still has a possible path forward in obese patients with medical complications, although that road would have many potholes. Whether US partner Eisai would be pleased with additional clinical trials or a smaller indication is not clear, although its chief executive did express continued support for Lorqess.

Fait accompli

Given the FDA’s tendency to agree with negative adcom votes, the complete response letter announced early Saturday morning was a fait accompli (Event - Obesity race enters the final straight, October 19, 2010).

The remaining question was whether FDA would yield to political sensitivities and kick the decision forward at least until the adcom had an opportunity to consider Orexigen Therapeutics’ Contrave, which has a review scheduled for December 7. The answer was an emphatic “no,” made easy perhaps by Lorqess’ efficacy and safety concerns.

Arena's chief executive Jack Lief put his best face on the situation by describing the document as “an important step for us toward the FDA's approval of lorcaserin.” But with the threat of additional trials to assess the safety of Lorqess, the odds of it coming to market soon look especially long.

The complete response letter asks Arena to provide more information related to breast cancer and adenocarcinoma in rats, along with information to model the risk of astrocytoma, a certain type of brain tumor, in humans. In addition, the FDA wants data from the Bloom-DM trial of lorcaserin in diabetics, as it describes its weight-loss efficacy in non-diabetics to be “marginal,” according to Arena’s release.

In the conference call, Arena executives would not be drawn on a timetable for supplying the data to the FDA, other than to state that they will be requesting a type A meeting for clarification of data requirements. Those meetings, if granted, are typically scheduled within 30 days of a request.

As for the specifics of the carcinogenicity data, the request asked Arena to explain the tumour mechanisms, which chief medical officer William Shanahan described as requiring short term studies.

Arena's shares edged 3% higher to $1.68 in early trade today, still significantly lower than the $7 they traded at before the negative adcom last month, suggesting investors do not share the optimistic outlook being spun by Arena's managers.

Reversal of fortune

Lorqess is the only novel product in the current crop of obesity candidates, and although it was thought to have the best safety profile, trailed on efficacy (Unpartnered obesity drugs under starter's orders at the FDA, April 23, 2010). Since release of its pivotal Blossom trial, there had been questions around whether lorcaserin had even met FDA's basic 5% weight-loss efficacy guidelines at all (Weaker data could mean slim pickings for Arena in the obesity market, September 18, 2009).

Vivus’ Qnexa had the best efficacy, although psychiatric safety concerns also derailed its day at the adcom, boding poorly for its PDUFA this week (Vivus sheds more weight after Adcom rejection of Qnexa, July 16, 2010). A complete response letter is also expected for Qnexa, although there is a chance the content of that letter will make for easier reading for the company and its investors.

With the obesity field a graveyard of drugs that caused as many health problems as they cured, safety was always going to be paramount. Unless and until Arena’s scientists can provide a good explanation about the cancer signals, that edge has gone.

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