Favourable market conditions.

The anti-obesity market is predicted to be worth $2.4 billion by 2021, growing 21% annually. High unmet need and advantageous epidemiological trends are key drivers. At first glance, the opportunity for new therapies seems considerable.

Limited success for Pharma so far.

For decades drug developers have had limited success in grabbing this opportunity. Many factors have contributed to the lacklustre performance of drugs that have made it to market so far.

Mediocre efficacy and lack of reimbursement.

There are many pathways involved in robustly ensuring energy homeostasis. Target one pathway, and others take up the slack. This helps explain the modest weight loss attributable to previous monotherapies. Targeting multiple pathways could be the way forward. But a shift towards polytherapy is challenging from a payer perspective. There’s already reluctance to reimburse long-term treatment for this sizeable patient pool, despite growing recognition of the high costs of treating obesity’s co-morbidities.

Safety issues raise the regulatory bar.

Then of course there are the side effects and serious safety issues. Think fen-phen in the early 1990s. Of the three drugs of the late 90s and early 2000s, only orlistat, with its unpleasant GI side effects, remains available. Sibutramine was withdrawn in 2010. Rimonabant never made it to the US market, and survived only two years in the EU. The regulatory bar is now far higher. Some view it as too high, querying the FDA’s risk/benefit calculations and lobbying for clarity of the regulatory pathway. No wonder Big Pharma took a step back from this increasingly uncertain arena.

Newcomers are welcomed, but are not magic bullets.

More recently biotech companies have taken up the challenge. The latest trio of treatments in the US to seek approval have moderate efficacy, and are beset with safety issues too. Not surprisingly all were initially rejected by the FDA. There are also market access issues. Two are combinations of off-patent medicines (Qsymia and Contrave). Limited insurance coverage for lifestyle diseases may see these losing out to the option of treating with two cheap generics rather than an expensive combination pill. In addition, Qsymia’s approval in 2012 came with the requirement of a Risk Evaluation and Mitigation Strategy, primarily over birth defect concerns, and its distribution is restricted to mail order. Belviq, an NCE monotherapy, approved around the same time, will probably be classified as a controlled substance. For Contrave, approval has yet to be given. CV safety trials are ongoing for all three.

Clinical optimism, but affordability pessimism.

It remains to be seen how successful these newcomers will be. They bring with them a new sense of optimism from a clinical perspective, and will pave the way for others in late-stage development. In particular the GLP-1 agonist liraglutide, which is already approved at a lower dose for type II diabetes. For the foreseeable future however, the key question of “who will pay?” will continue to be answered in the main by “affluent patients”. Public payers will remain extremely unwilling to fund treatment, for what many regard as a lifestyle disease, in all but those at the highest risk. This will continue to prevent obesity treatments gaining their full market potential.

Want to Dig Deeper?

The pharmaceutical market for obesity therapies. G. Heap et al. Nature Reviews Drug Discovery 11, p669-670, 2012

FDA Approval of Obesity Drugs. A Difference in Risk-Benefit Perceptions. E. Morrato & D. Allison. JAMA 308. p1097-1098, 2012