Will Regulators Stop the Development of Anti-Obesity Drugs?

Regular readers may recall that I was recently called upon to present at an advisory meeting of the US Food and Drug Administration (FDA) on whether or not the obesity drug sibutramine should remain on the US market.

Readers may also recall that the vote resulted in a tie that did not stop the FDA from requesting that Abbott Laboratories “voluntarily” withdraw sibutramine from the US market.

Two other FDA advisories held this year for anti-obesity drugs also did not turn out to be positive for the sponsors.

As I, and many other observers of these proceedings, have commented, there is growing concern about the process by which the FDA (and other regulators) comes to these decisions. In fact, this process may well prove to be a major stumbling block that can stifle any further research into finding safe and effective anti-obesity drugs.

Given the remarkable failure of “Eat-Less-Move-More” (ELMM) strategies to demonstrate any lasting effect on reducing obesity rates, finding effective pharmacotherapy for obesity remains one of the most glaring and pressing unmet health care needs of our times.

As I have said before, the lack of effective obesity drugs will do little more than leave millions of people struggling with excess weight scraping together the funds to pay for the services of their friendly neighbourhood surgeon.

But the FDA is by no means alone in its rather negative (or perhaps over-cautionary) view of anti-obesity drugs. In fact, the European regulatory agency, made up its mind to banish sibutramine even before the data from the key study (SCOUT) had been fully analysed, let alone published.

These recent decisions prompted me and a few of my European colleagues to write an editorial on this issue, which has now been published online in Obesity Reviews.

The following excerpts are taken from this editorial:

“Over the past 4 months, the United States Food and Drug Administration (FDA) Endocrine and Metabolic Advisory Committee (EMDEC) met three times to evaluate antiobesity drugs. In all three cases, the outcomes were not favourable for these agents; in fact, the split vote for sibutramine was by far the most positive result.

Although the FDA may ultimately approve these agents, many aspects of these meetings are worrisome for the obesity community and warrant close scrutiny.

The first matter of concern is the composition of the EMDEC panels. For one, there was no currently practicing obesity expert on the EMDEC roster.

This situation is remarkably different from the FDA’s practice in other areas of medicine like oncology or cardiology, where Advisory Committees are composed largely of practicing doctors who actually see the target patients for new medications on a regular basis, and are therefore, in a much better position to evaluate potential risk/benefits of the agents under review.

Furthermore, there was an obvious lack of expertise on the panels for certain very specialized safety issues identified during the FDA review for each compound. This begs the question of how these advisors can be expected to make informed decisions regarding the risks/benefits of these compounds.

The fact that companies spend hundreds of millions of dollars on the development of these agents, while thousands of patients volunteer to test them, only for the fate of these efforts to be largely decided by a panel with inadequate expertise in the very issues that are to be decided is highly disconcerting.

Second, the panelists repeatedly asked for data outside of the current FDA Guidance for development of weight loss agents. The FDA publishes its guidance documents as templates for pharmaceutical companies to follow if they want to obtain the desired indications for their compounds. Not surprisingly, the companies stick to these documents to the letter. In addition, every Phase 3 programme is also discussed in detail with the FDA during so-called End of Phase 2 meetings.“

As we go on to state:

“The panelists repeatedly criticized the sponsors for recruiting ‘sanitized populations’, ‘not the typical obese’ patients or not the ‘typical patients coming to their offices’ and thus declared the data not ‘applicable to the real world’. In reality, all of these programmes included exactly the populations required by the FDA Guidance and were agreed upon by the FDA prior to the start of the Phase 3 programmes.“

Based on the many positive responses we received from colleagues, who have had a chance to read the editorial, we feel that we are justified in our concerns.

If the FDA (and other regulatory agencies) continue holding anti-obesity drugs to higher standards than drugs for other serious medical conditions, they are only perpetuating the notion that obesity is not a medical condition serious enough to warrant even the most minimal risks of pharmaceutical treatment.

This flies in the face of the reality that obesity most evidently is a condition dangerous enough to warrant the very real risks of bariatric surgery.

Forcing the pharmaceutical industry to abandon the development of obesity drugs due to “futility” is nothing short of a disservice to the millions who struggle with obesity everyday.

As I have said before, no obesity drug will ever be found to be safe enough to be taken by the wrong people for the wrong reasons. If that is the bar to which pharma companies will be held, the future for anti-obesity drugs is bleak indeed.

AMS
Deerfield, Illinois

Disclaimer: I have received research funding as well as consulting and speaking honoraria from several pharmaceutical companies involved in the development and marketing of anti-obesity drugs.

Dvorak RV, Sharma AM, & Astrup A (2010). Anti-obesity drugs: to be or not to be? Obesity reviews : an official journal of the International Association for the Study of Obesity PMID: 21054758