More Progress with a Super Targeted Obesity Drug

Two years ago, Rhythm Pharmaceuticals made a big splash with a study showing impressive efficacy for their super targeted obesity drug, setmelanotide. That paper in the New England Journal of Medicine showed setmelanotide could reverse obesity in patients with a rare POMC gene defect. Now, researchers have published new data showing promise in patients with another rare genetic defect – leptin receptor deficiency.

Of course, these are small studies – just three patients in the latest study. The genetic defects under study are rare and devastating. Because of this defect, patients suffer with insatiable hunger and severe obesity. These symptoms show up early in life and resist conventional treatments. Yet in the latest study, patients lost 10-20% of their starting weight.

A New Pathway for Treating Obesity

Setmelanotide acts to stimulate very specific receptor in the brain called a melanocortin-4 receptor. So scientists call it an MC4R agonist. Research suggests that these receptors lie in a critical pathway for regulating appetite and body weight. In this pathway, many different hormones – leptin, ghrelin, NPY, and AgRP – interact to regulate energy balance and, thus, body weight.

Because this pathway has such importance for regulating energy balance, it’s become a subject of intense focus for obesity researchers.

An Encouraging Milestone

This milestone provides encouragement in two ways. It suggests the drug can work with yet another type of obesity. And it shows that the responses can last for up to a year. Yet much work lies ahead. Phase 3 studies are ongoing. These studies will provide an important foundation of evidence for safety and efficacy in both POMC deficiency and leptin deficiency. The company expects to have data for the POMC indication in the first half of next year. If all goes well, an application for FDA approval could follow soon afterwards.

Pointing to the Promise of Precision Obesity Care

But perhaps the most important development we’re seeing is a confirmation that obesity is not a single disease. It comes in many different forms. As a result, no one single form of treatment will deliver ideal results for every patient. We need obesity care tailored to the physiology of individual patients.

Right now, obesity medicine physicians and other skilled care providers do this through trial and error. However, the science is accumulating to permit ever more precise approaches.

Click here for the study in Nature Medicine and here for further perspective from FierceBiotech.

Target, photograph © 8 Kome / flickr

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May 11, 2018

4 Responses to “More Progress with a Super Targeted Obesity Drug”

  1. May 11, 2018 at 9:08 am, Angie Golden said:

    Thank you for this information. I really enjoy the diversity your writing brings. Of course, not just physicians are treating obesity. NPs and PAs are as well 🙂 through trial and error with the attempts at precision in both medications and the correct eating plan for each individual patient.
    Dr. Angie Golden, Family Nurse Practitioner

    • May 11, 2018 at 11:17 am, Ted said:

      You are right, Angie. I appreciate the reminder that it takes many kinds of skilled providers to deliver effective obesity care, Angie.

  2. May 19, 2018 at 11:03 pm, Ajit Venniyoor said:

    I don’t agree with the author’s statement that “obesity is not a single disease….., no one single form of treatment will deliver ideal results for every patient.”. It is like saying that lung cancer is not a single disease. True, at a molecular level, there are multiple mutations that cause lung cancer and treatment can be tailored to target these driver mutations (such as mutations involving EGFR, ALK, ROS, BRAF, Her2, etc). But the vast majority of lung cancers occur in smokers, do not have driver mutations, and is preventable
    Similarly, though a small percentage of obesity can be due to rare mutations (such as those mentioned in the article) and endocrine causes, the vast majority are due to lack of exercise and over eating. Statements such as these are self defeating as they provide obese patients with an excuse not to control their weight by simple measures, while they wait for their “rare mutation” to be detected and targeted.

    • May 20, 2018 at 4:30 am, Ted said:

      Thanks Ajit, for sharing your views. The causes of obesity are far more complex than you might believe. If you want to know more, this Viewpoint from JAMA would be a good place to start:

      Patients are looking for help, not excuses. And when I hear a healthcare professional blaming a patient for a health problem, it sounds a lot like an excuse for being unhelpful.