After many years of significant research and development investment offset by pipeline failures and development setbacks, the obesity market yesterday (28 June) finally saw the FDA approval of a new treatment: Arena Pharmaceutical and Eisai's lorcaserin, to be branded as Belviq.
IHS Global Insight Perspective | |
Significance | Given the scale of the public health issues related to obesity and overweight patients, as well as the knock-on healthcare problems associated with the condition, the approval of a new treatment option here represents a significant breakthrough, with physicians struggling with few alternatives at their disposal. |
Implications | Although the availability of Belviq is a significant positive for Arena and Eisai, the US FDA's approval comes with notable conditions, including an enforced suspension of treatment on patients without visible results after 12 weeks; a demand for six post-marketing studies, including echocardiography testing; and the classification of the drug as a controlled substance; which will delay launch. |
Outlook | Alongside the significant conditions associated with the approval, significant uncertainty remains in terms of the size of Eisai's sales force to market a drug in a disease that requires such substantial promotional commitment, as well as how willing payors and insurance firms will be to reimburse the treatment, which has proven to inhibit growth of other treatments in this area significantly. Still, the FDA's stance appears to indicate a willingness to approve these treatments, which, although competing against each other, will largely be seen as creating a new market. As such, Belviq's approval represents a positive for Qnexa and Contrave, the other key obesity candidates awaiting final regulatory review. |
The US FDA yesterday (28 June) announced that it has approved serotonin 2C receptor activator Belviq (lorcaserin hydrochloride) as an addition to a reduced-calorie diet and exercise for chronic weight management; the drug will be marketed by commercial partners Arena Pharmaceutical (US) and Eisai (Japan). Belviq will be used in adults with a body mass index (BMI) of 30 or more (defined as clinically obese) or adults with a BMI of 27 or more (defined as clinically overweight) with at least one weight-related condition such as high blood pressure, type 2 diabetes, or high cholesterol. Dosing is twice daily with oral treatment, and Belviq's labelling recommends discontinuation in patients who do not lose 5% of their body weight after 12 weeks of treatment. The FDA's decision follows on from an assessment of three randomised, placebo-controlled trials that included 8,000 obese and overweight patients treated for between 52 and 104 weeks; treatment with Belviq for up to one year was shown to increase weight loss by 3–3.7% versus placebo, and around 47% of non-diabetes patients lost at least 5% of body weight compared with 23% on placebo. The FDA's decision is available here.
The approval comes 20 months after the FDA failed to recommend the treatment in October 2010, following its original assessment of the risk-benefit of the drug. The FDA noted that there is no evidence that Belviq activates the serotonin 2B receptor in its 10-mg twice-daily dosing; this problem is thought to lay behind the heart valve damage that resulted in the withdrawal of weight-loss drugs fenfluramine and dexfenfluramine in 1997. It has imposed a relatively stringent pharmacovigilance agenda on Eisai and Arena, however, involving six post-marketing studies (PMS): one of these will assess long-term cardiovascular outcomes, including serious adverse cardiac events such as heart attacks and strokes, and there will be five paediatric trials. The PMS will also involve echocardiography, which significantly increases complexity and cost. There is no risk evaluation and mitigation strategy (REMS) associated with the approval though.
The approval follows on from the 18–4 vote in favour of the safety and efficacy of the drug in May. Eisai, which licensed US rights to the drug in July 2010 and expanded this to other Americas rights, is expected to have around 250 primary care medical representatives dedicated to Belviq, which represents a relatively small commitment in a market that requires significant promotional support. As expected, the drug will also be a scheduled drug, classified as a controlled substance, which will require an additional review from the Drug Enforcement Administration (DEA) of around six months. This will probably mean that a launch will not be seen until the new year.
Outlook and Implications
The approval means Arena and Eisai could maintain a first-mover advantage over Vivus' Qnexa (phentermine + topiramate) and Orexigen Therapeutics' Contrave (naltrexone + bupropion), although the DEA review may prevent the companies from achieving this. Qnexa and Contrave are the next candidates in this market, which were also subjected to FDA non-approvals in October 2010 and January 2011, respectively. These regulatory setbacks raised significant questions as to whether any new drug will reach this difficult but potentially lucrative market. The initial complete response letter on Belviq called for more data in diabetic patients, as well as an assessment on cancer risks in rats, and although Arena and Eisai have addressed these concerns, the FDA continues to have a cautious stance on the safety and risk-benefit of a drug that could potentially be subject to misuse and have widespread uptake in the absence of significant conditions attached to the approval. Qnexa looks like it could be the next drug on the market following the FDA panel recommendation in February: the Prescription Drug User Fee Act date is 17 July. The drug is generally seen to have a better efficacy profile than Belviq, but also appears to have more side-effects; unlike Belviq, it is being subjected to a REMS programme.
Alongside the conditions associated with the Belviq approval, significant uncertainty remains both in terms of the size of Eisai's sales force to market a drug in a disease that requires such substantial promotional commitment and how willing payors and insurance firms will be to reimburse the treatment; this latter obstacle has proven to inhibit growth of other treatments in this area significantly. Clearly, physicians tend to prefer lifestyle changes—both dietary and physical—as the most significant treatment option for obesity and weight management. Consumer demand clearly lends itself towards pharmaceutical treatment though, at least in addition to diet and exercise, and there will now be significant consumer pressure to ensure the availability of the new treatment. Payors may resist this pressure, however, which could significantly reduce uptake. In theory, the obesity market in general, and the Belviq opportunity in particular, would be a blockbuster opportunity, but the conditions attached to the approval and uncertainty over reimbursement have led to general market expectations of peak sales of around USD500 million.
Related Articles
- United States: 11 May 2012: Lorcaserin Receives Positive Recommendation from US FDA Panel
- United States: 10 May 2012: FDA Panel Favours Tofa, Rejects Arcalyst in Gout Flares, Debates Linger on Locaserin and Quad
- United States: 23 February 2012: Qnexa Secures FDA Advisory Committee Recommendation for Approval
- United States: 5 January 2012: Arena Pharma and Eisai Pursue Lorcaserin Drug Application in US
- United States: 22 September 2011: Orexigen Revives Hope for Obesity Drug
- United States: 3 February 2011: FDA Sends Back Takeda's Contrave, Requests Another Clinical Study Due to Cardiovascular Concern
- United States: 25 October 2010: FDA Issues Complete Response Letter for Arena's Anti-Obesity Drug