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Rhythm Pharma’s Obesity Drug Hits Phase 3 Goals, FDA Filing Planned

Xconomy Boston — 

A Rhythm Pharmaceuticals drug developed to reduce the weight gain and ravenous hunger in genetic obesity disorders has hit the goals of two late-stage clinical trials, and the company now plans to file for FDA approvals late this year or in early 2020.

On Wednesday, Rhythm (NASDAQ: RYTM) announced preliminary Phase 3 data for its drug, setmelanotide, in two rare, inherited obesity disorders: pro-opiomelancortin (POMC) deficiency and leptin receptor (LEPR) deficiency. In both diseases, the Boston company said its drug hit the main goals of weight reduction. Of the patients who didn’t lose enough weight to achieve the study’s main goal, Rhythm said some still reported meaningful reductions in hunger.

The company’s stock price jumped more than 19 percent to $22.63 on the news.

Rhythm’s drug targets the melancortin 4 receptor, or MC4, a protein that plays a role in regulating appetite and weight. In rare genetic obesity disorders such as POMC and LEPR, this protein does not function properly, leading to insatiable hunger that causes patients to overeat and become severely obese early in life.

Setmelanotide is an injectable peptide drug developed to boost the activity of MC4. Rhythm tested its drug in open-label, single-arm studies enrolling patients 6 years of age or older. The main goal of both one-year studies was achieving 10 percent weight loss compared to historical measures of this patient population. Secondary goals included reductions in body weight and hunger measured according to a hunger rating scale.

In POMC, Rhythm reported that eight of 10 patients achieved the study’s main goal. On average, patients lost 25.4 percent of their weight. The average reduction in the hunger rating score was 27.9 percent. After one year of treatment, the average weight loss was 70.2 pounds. Of the two patients who did not meet the main weight loss goal, Rhythm said one had other health problems that made it difficult to assess the response to the drug. The other patient had a genetic variant that may not be related to POMC, the company said.

In LEPR deficiency, five of 11 patients hit the main goal of 10 percent or greater weight reduction. The average weight loss in this group was 12.5 percent; the average reduction in hunger rating score was 41.9 percent. LEPR deficiency patients in the study lost an average 36.8 pounds in one year.

Of the six patients that did not achieve the main goal of the LEPR study, Rhythm said the data suggest that three did not receive the correct dosing, and all three experienced substantial weight gain after they stopped receiving the drug at the end of the study. A fourth patient stopped treatment early due to side effects. And the fifth and sixth patients had other health problems that made it difficult to assess the effect of the drug, according to Rhythm.

Side effects included reactions at the injection site, as well as nausea and vomiting. The patient who withdrew experienced mild hypereosinophilia, a blood disorder characterized by high numbers of white blood cells.

The reduction in the hunger scores translates to a tangible improvement in patients’ quality of life, Murray Stewart, Rhythm’s chief medical officer, told analysts on a conference call. “They’re not raiding the cupboards anymore,” Stewart said.

CEO Keith Gottesdiener said on the conference call that even though some patients did not hit the weight-loss goal established for the studies, their reduction in hunger is meaningful. He added that the company has spoken with regulators about the importance of that measure in the lives of patients, adding that “it’s our impression that the FDA will be open to it overall.”

Rhythm expects to publish the full Phase 3 data in the fourth quarter of this year. At that point, the company will be preparing to file a “rolling” submission to the FDA for both POMC and LEPR. A rolling review means that a company can submit sections of the application as they are completed, rather than waiting for the entire application to be finished.

Setmelanotide is also being tested as a treatment for two other rare, genetic obesity disorders: Bardet-Biedl syndrome and Alström syndrome. The company expects to complete enrollment for those Phase 3 studies in the second half of this year.

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