As has been the case for many years, it is a case of two steps forward and one step back for the obesity market. Despite the tremendous market potential, a bona fide medical therapy for obesity has yet to establish itself. Potential blockbusters come and go, but therapeutic options remain limited. Off-label use of prescription medications, including SGLT-2 inhibitors and GLP-1 receptor agonists, is not uncommon as approved treatments can be ineffective, unaffordable, or intolerable.

The slim pickings from the late-phase obesity pipeline just got slimmer…

Zafgen’s beloraninb had looked particularly promising in early phase trials, but as predicted by DRG, development has been terminated. Despite demonstrating remarkable efficacy in terms of weight loss and reductions in hunger in patients with Prader-Will Syndrome and severe obesity, the occurrence of VTE events in patients receiving the drug during the Phase III program have unsurprisingly tipped the balance in favour of discontinuation. Although Zafgen were targeting patients with rare and severe disease, the risk-benefit profile for beloranib was unlikely to ever convince regulators, regardless of the underlying risks from obesity faced by potential recipients. The chequered history of obesity drug development mean that emerging prescription weight loss therapies get more scrutiny than most. Unfortunately, in many instances, the targets for reducing appetite and/or increasing satiety appear to come at the expense of cardiovascular or neuropsychiatric side effects, and authorities are increasingly interested in seeing safety and efficacy outcomes data prior to approval.

…but hope springs eternal

However, two new Phase II candidates are emerging with clinical promise and big pharma backing. Janssen are developing canagliflozin and phentermine in combination as a weight loss therapy. Phase II data presented at ADA 2016 demonstrate placebo-adjusted weight loss of up to 6.9% after 26% weeks, suggesting similar efficacy to already approved agents. Novo Nordisk also list semaglutide, their once-weekly oral GLP-1 agonists as in Phase II for obesity. Should the development of semaglutide continue in the same vein as liraglutide (Victoza/Saxenda), then another potential weight loss therapy could emerge. With physicians already confident about prescribing SGLT-2 inhibitors and GLP-1 receptors agonists, and many patient-years of experience now accrued with such agents, a sensible pricing strategy could see them rapidly gain traction in the market should their Phase III data confirm the expected risk-benefit profiles. Moreover, DRG’s forecast for the U.S. obesity market suggests that off-label use of SGLT-2 inhibitors and GLP-1 receptors agonists is likely to continue, despite the availability of several approved therapies (see figure).

 US off-label sales

In-depth analysis of obesity, with accompanying epidemiology driven sales forecast models, is presented in Decision Resources Group’s Obesity/Overweight Insights, available here.

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