“Showing additional CV benefits is important for obesity therapies. It will hopefully remove some of the stigma against these drugs as being purely ‘cosmetic’”
-Thought leader, United States
In what has been a relatively quiet year for the obesity market, save for Orexigen’s bankruptcy in March, August brought with it the results of the long-awaited CV outcomes trial for Eisai’s Belviq (CAMELLIA–TIMI; NCT02019264), presented at this year’s European Society of Cardiology Congress in Munich and subsequently published in the NEJM1. Despite not showing any positive CV benefits to patients, the trial did confirm that long-term treatment with Belviq was not detrimental to CV health, in comparison to placebo. Given the shadow of harm caused by Fen-Phen almost 3 decades ago still hangs heavily over the obesity space, the ability to show non-inferiority to placebo in terms of CV safety is, in itself, an important milestone. Although the mainstream media proclaimed Belviq the “holy grail” in the fight against obesity following the results, it is unlikely to be the silver bullet in tackling the growing global epidemic.
Fall From Grace
Belviq was first approved by the FDA in June 2012 and became available on the U.S. market in early 2013. In May 2013, its European marketing authorization application was withdrawn by Arena Pharmaceuticals (Eisai’s co-development partner at the time). The EMA raised concerns over potential carcinogenicity, the potential risk of psychiatric disorders, such as depression, and valvulopathy. In addition to the CV results in the CAMELLIA–TIMI trial, suicidal ideation was noted in 21 patients in the treatment group (N = 5,995) and 11 of the placebo group (N = 5,992), although Eisai noted “the numerical imbalance in suicidal ideation or behavior appeared to be restricted to patients with depression at baseline”.
Whilst Belviq did initially lead the pack of anti-obesity agents in terms of sales, albeit in a fairly barren landscape, reaching peak year sales in 2014 of approximately $50m, its revenue quickly began to decline as it was eroded by agents offering greater weight loss, often at greater discounts. Belviq has never recovered from this slump, currently languishing with annual sales comparable to that of the much-maligned Xenical. A summary of Belviq’s competitors can be seen in the table below.
- a) Data leveraged from LEADER CVOT for Victoza in patients with type 2 diabetes (Novo Nordisk, press release, August 25, 2017)
- b) Retrospective analysis of previous data. Vivus are using this strategy to try and minimize/mitigate the need to undertake an additional post-marketing CVOT (Vivus, press release, August 27, 2018).
“Weight loss is one thing, but if the drug is doing something else to benefit the patient in terms of CV outcomes, that’s something else. That is really important”
-Thought leader, Germany
Too Little, Too Late?
Showing that Belviq is not damaging to CV health is undoubtedly a positive gain for the franchise and is likely to cause an, albeit modest, uptick to its sales in the United States. However, KOLs interviewed by DRG in the United States and EU frequently state that although they consider the drug to have an acceptable safety profile, weight loss efficacy in practice is often poor. Indeed, the CAMELLIA–TIMI trial showed that patients treated with Belviq lost just 4.2kg (compared to 1.4kg loss in the placebo group), equating to an average 4% weight loss, below that of the 5-10% loss recommended in treatment guidelines. In addition, questions still remain surrounding Belviq’s effect on psychological health, in addition to concerns regarding its carcinogenicity. Given these concerns, we predict that it is highly unlikely that Eisai will resubmit Belviq in Europe, limiting its revenue stream to a small pool of countries including the United States, Mexico, Brazil, and Taiwan.
CV outcomes and efficacy aside, the CAMELLIA–TIMI trial does shine the spotlight on the disparity between the companies in the obesity space. Large-cap companies such as Eisai and Novo Nordisk have the vast resources at their disposal to run large, expensive CVOT trials, to ultimately benefit the reputation of their drugs. In contrast, their micro-cap competitors continue to struggle – Vivus recently announced a retrospective analysis of its clinical data to show CV safety of Qsymia, a move to try and mitigate a long and expensive post-marketing CV outcomes trial, as mandated by the FDA.
With companies such as Novo Nordisk being able to show far stronger weight loss efficacy and positive CV outcomes data with both Saxenda and semaglutide (in addition to efficacy in related metabolic diseases such as diabetes and NASH), the question remains: how long can drugs with poor efficacy and questionable safety profiles be tolerated by physicians, patients, and payers in an increasingly competitive market?
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- Bohula EA et al. Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients. N Engl J Med. 2018 Aug 26. doi: 10.1056/NEJMoa1808721. [Epub ahead of print].
- Novo Nordisk, Annual Report 2017, March 22, 2018.
- Orexigen, press release, April 23, 2018.
- Vivus, Form 10K, February 28, 2018. Pg 78.
- Eisai, FY 2017, Full Year Financial Results, May 15, 2018.
- Decision Resources Group, Company and Drug Insights, Accessed August 30, 2018.