Global Insight Perspective | |
Significance | An FDA advisory committee has decided not to recommend Sanofi-Aventis's drug Zimulti/Acomplia (rimonabant) for weight-loss use in obese and overweight patients with associated risk factors. |
Implications | The committee's decision is based on findings revealed by the FDA earlier this week, of an apparent link to suicidal behaviour in some Acomplia users during clinical trials. The FDA's final decision is due on 26 July, and the organisation is likely to back the findings of the committee. |
Outlook | An FDA refusal would be a significant setback for Sanofi's plans to turn Zimulti/Acomplia into a blockbuster, and the safety issues linked to the drug could also damage the drug's sales growth overseas. Sanofi-Aventis is expected to present more data to the FDA, possibly including user data from countries where the drug is already being used, before re-filing for U.S. approval; a process that could take years. |
The door is shutting fast on Sanofi-Aventis's weight-loss drug Acomplia (rimonabant) in the United States, after the FDA's Endocrinologic and Metabolic Drugs Advisory Committee chose not to recommend the product—known as Zimulti in the United States—for approval as a treatment for obese and overweight patients with associated risk factors. The FDA itself still has the opportunity to rule against the committee's decision on 26 July, the PDUFA (Prescription Drug User Fee Act) action date set by the organisation for issuing a final verdict on whether to approve Zimulti. However, history suggests that the FDA is highly likely to follow the recommendation of its advisory committee.
The committee's verdict on Zimulti came just days after the FDA revealed that a 20-mg dose of the drug had a statistically significant link to incidences of adverse psychiatric events including suicidal thought or behaviour during placebo-controlled clinical trials (see France: 12 June 2007: Suicidal-Thoughts Link Threatens Sanofi-Aventis's Acomplia After New U.S. FDA Review). From the outset, rimonabant was touted as a first-in-class drug, a member of the selective cannabinoid type 1 (CB1)-blockers class, which blocks off the brain receptors that control appetite rather than working with the gastrointestinal system, as most weight-loss drugs do. It now seems that the treatment's mode of action has raised enough concerns over potential suicidal behaviour for the U.S. authorities to decide against approving it for marketing.
Yet in spite of this, Acomplia/Zimulti has already been granted regulatory approval in some 37 countries around the world, and is presently on sale in 18. These countries' drug supervisory authorities would have had access to the same clinical trial data as the U.S. FDA, and yet did not hesitate in approving Acomplia for use as an obesity treatment. With an FDA rejection on safety grounds now likely, it remains to be seen what effect the refusal will have on Acomplia's fortunes overseas. A complete market withdrawal is not on the cards, but the European Medicines Agency (EMEA) may be inclined to ask Sanofi-Aventis for additional safety data or may even conduct an in-house review of the existing data in order to potentially beef up the warning level on the drug's European label. Additionally, as news of Acomplia's link to the risk of psychiatric events filters down to the general public, a reluctance to use the drug may form, potentially resulting in slower sales growth than hoped for.
Outlook and Implications
Sanofi-Aventis will have its work cut out in what promises to be an important exercise in damage-control. The French pharmaceutical giant has said that it intends to continue working in conjunction with the FDA "to address the committee's recommendations". An FDA refusal to approve the drug is almost certain at this point, and will have a significant impact on Sanofi-Aventis's plans for Acomplia's global marketing. The weight-loss product—once touted by analysts as a potential miracle cure for anything from weight-loss to nicotine addiction—was estimated to eventually bring in peak annual sales of 3 billion euro (US$4 billion), making it a guaranteed blockbuster that would be crucial to Sanofi-Aventis's future success. The first quarterly sales figures for Acomplia came after the first three months of 2007, during which time the drug brought in some 15 million euro in global revenue. While many key European markets have approved Acomplia for marketing, only three—France, Switzerland and Sweden—have also agreed to reimburse it; another major factor behind its slow market penetration to date.
Despite the likely FDA rejection, Sanofi-Aventis is not expected to sound the death-knell for Zimulti in the United States just yet. With the Centers for Disease Control & Prevention estimating that 30% of adults aged 20 and older (or 60 million people) are clinically obese, the potential for Zimulti to succeed in the United States remains considerable. Once the FDA has issued its final opinion on the matter, Sanofi-Aventis is likely to submit additional data on Zimulti, potentially including user data from countries where the drug is already being used. It will then attempt to re-file Zimulti for U.S. approval. The whole process could take years to complete, and even if and when Zimulti is eventually approved, it will have the likes of GlaxoSmithKline's (U.K.) OTC (over-the-counter) competitor Alli (orlistat)—by then firmly established on the market—to contend with. The FDA, for its part, may be inclined to issue another approvable letter to Sanofi-Aventis, rather than a non-approvable one, which could shorten the time to a re-filing by specifically listing additional data required. However, given the continued scrutiny of the FDA in the wake of the Vioxx (rofecoxib) and Celebrex (celecoxib) safety scares, the organisation is likely to err on the side of caution in the case of Zimulti, particularly given the nature of the concerned side-effects.