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Amgen, Wyeth Defy Odds as U.S. FDA Advisory Committee Recommends Approval for Paediatric Enbrel
20 Jun 08
Enbrel clears the first hurdle on the way to U.S. approval, but as an anti-TNF drug still faces a major challenge in the shape of an FDA safety review.
Global Insight Perspective | | Significance | The U.S. FDA's Dermatologic and Ophthalmologic Advisory Committee (DODAC) has voted to recommend Amgen's drug Enbrel for approval as a treatment for paediatric patients with moderate-to-severe plaque psoriasis. | Implications | Despite the majority vote, there remains uncertainty within DODAC over the drug's potential link to cancer and infectious disease. Amgen has proposed a risk-management scheme to inform patients and alleviate concerns. | Outlook | The FDA is currently reviewing the wider anti-TNF drug class—of which Enbrel is a part—and assessing the strength of a link to cancer in paediatric patients. If the link is proven to be stronger than that already noted in adults, Enbrel's approval is unlikely to materialise despite its proven efficacy. |
An advisory committee to the U.S. FDA has voiced support for the approval of a paediatric formulation of psoriasis drug Enbrel (etanercept), produced by Amgen and co-marketed by Wyeth Pharmaceuticals. Both the FDA itself and the two U.S. drug-makers have confirmed that the Dermatologic and Ophthalmologic Drug Advisory Committee (DODAC) voted eight to five in favour of extended the drug's approved indications to include the treatment of patients aged between four and 17 years with chronic moderate-to-severe plaque psoriasis. The recommendation is an important step on the way to a potential FDA approval for Enbrel's new indication, which Amgen and Wyeth have been seeking since they first filed a supplementary Biologics License Application (sBLA) for the drug in September 2007. Enbrel's Black Box Label (partial text) | WARNING RISK OF INFECTIONS Infections, including serious infections leading to hospitalization or death, have been observed in patients treated with Enbrel (…). Infections have included bacterial sepsis and tuberculosis. Patients should be educated about the symptoms of infection and closely monitored for signs and symptoms of infection during and after treatment with Enbrel. Patients who develop an infection should be evaluated for appropriate antimicrobial treatment and, in patients who develop a serious infection, Enbrel should be discontinued.
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The eight-to-five split of the DODAC vote suggests persistent concerns within the advisory committee as to Enbrel's safety. Indeed, according to FDA News, several DODAC members would have preferred the recommendation for Enbrel's paediatric form to be limited to severe cases of psoriasis, rather than moderate-to-severe. Enbrel, which is already approved for various forms of arthritis, ankylosing spondilitis, and psoriasis in adults, was hit with a black-box warning last month. The black box is the strongest form of warning label that the FDA can impose on drug packaging, and in Enbrel's case it mentions the risk of developing serious infectious diseases such as tuberculosis (see United States: 2 May 2008: Black-Box Label for Enbrel as Amgen and Wyeth Warn Of TB Risk). More recently, the FDA has begun a review of the risks associated with anti-tumour necrosis factor (anti-TNF) treatments—the drug class to which Enbrel belongs—after growing evidence suggests that they could have a possible link to cancer in children and young adults (see United States: 5 June 2008: FDA Reviews TNF Inhibitors' Link to Cancer in Children, Young Adults). Secondary votes taken during the DODAC meeting revealed that while 12 committee members agreed (one abstained) that Amgen successfully demonstrated Enbrel's efficacy in treating paediatric psoriasis, only four members believed that the biotech had provided enough information on the potential risk of malignancy. To counter some of these concerns, Amgen has proposed a risk-management programme to DODAC, under which prescribers, patients, and their parents or guardians would be educated as to the potential risks of taking the drug. According to the biotech, some 7.5 million people in the United States have psoriasis, with approximately one-third developing the condition during childhood. Despite this, Amgen says that paediatric psoriasis patients are underserved by the market, with no topical or systemic psoriasis treatments approved for chronic paediatric use. Amgen's U.S. sales of Enbrel grew by 11.5% year-on-year (y/y) and reached US$3.1 billion in 2007, positioning it as the top-selling drug in light of plummeting sales of the company's anaemia franchise (see United States: 25 January 2008: Amgen Posts Slow but Steady Full-Year Growth Despite 2.3% Revenue Dip in Q4). According to IMS Health, Enbrel was also the seventh biggest drug in the United States by sales last year, from any company. Outlook and Implications The green light from DODAC is excellent news for both Amgen and Wyeth, but it does not necessarily imply a straightforward marketing approval from the FDA. While the agency does tend to agree with the verdict of its advisory committees, it is not under any obligation to follow their advice. If the FDA decides that further safety data are required, one possible course of action could be to demand a post-marketing study taken from existing off-label use of Enbrel in paediatric patients. This would come as a blow to Amgen in particular, requiring more funding to be injected into a Phase IV trial, while a potential approval would be delayed by at least a year. A more drastic approach would be for the FDA to issue a non-approvable letter, effectively refusing to approve Enbrel for marketing in a paediatric setting. While the potential link to cancer is already mentioned on the U.S. labelling of all anti-TNFs, the outcome of the FDA's ongoing review may determine that the link is stronger in paediatric patients, in which case the agency would almost certainly refuse to endorse the approval of Enbrel for this patient population and could also choose to clamp down on off-label prescribing.
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