Rhythm Pharmaceuticals scores first FDA approval for obesity med targeting genetic defects

FDA Building
The FDA signed off on Rhythm's new rare disease med targeting obesity. (FDA)

Obesity is a major problem worldwide, but, for a fraction of patients, genetic mutations rather than habits are driving the disease. With its new FDA approval for Imcivree, Rhythm Pharmaceuticals is taking the first step toward treating those cases.

For a subset of obesity patients, genetic mutations leave them with an “insatiable hunger,” Rhythm CEO David Meeker, M.D., said in an interview. Early onset genetic diseases can leave patients unable to control obesity with diet and exercise, and, now, Rhythm has scored the first FDA approval for a targeted medicine aimed at treating them.

Imcivree, formerly known as setmelanotide, scored an FDA nod to treat patients who have variations of the POMC, PCSK1 or LEPR genes. The drug targets the MC4R pathway responsible for regulating hunger, and the three genes included in the initial approval are just a first step, Meeker said. The company developed a test that looks at about 100 genetic mutations, and it’s testing the medicine in other genetic mutations with eyes on potential approvals down the line.

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With obesity, “you can see the forest,” Meeker said, because the problem is everywhere. The challenge is finding patients who could have an underlying genetic mutations causing excessive hunger, he said, noting that “testing becomes key.”

Most people, and most doctors, still think of obesity as a “calories in, calories out,” problem, said Michael Dedekian, medical director of pediatric specialty care at Barbara Bush Children’s Hospital in Maine. Very quickly, though, the medical community’s understanding of obesity is deepening, he said. And, as that’s happening, it’s becoming clear that genetic defects can “wildly disregulate” patients’ hunger.  

With the approval and new knowledge about genetic defects, Dedekian believes the medical community is entering a “whole new era of obesity treatment." Over time, he has no doubt awareness of the genetic mutations driving some cases will increase. When abnormal hunger presents itself in young children, doctors should strongly consider a genetic test, Dedekian said.

Rhythm isn’t planning to deploy a sales force for its initial genetic mutations and will instead focus on “intensive efforts” around disease education and making its test more available, Meeker said. When doctors are confronted with a patient with abnormal hunger, they should be “thinking deep” about the cause, he added.

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The company was originally formed as Rhythm Metabolism, and in 2016 sold a subsidiary called Motus Therapeutics to Allergan for $200 million on the heels of phase 2b data for diabetic gastroparesis treatment relamorelin. Following the deal, Rhythm focused on genetic disorders that cause obesity. Rhythm licensed Imcivree from Ipsen back in 2010.

Aside from its first approval, Rhythm is studying Imcivree in two other genetic defects in phase 3 testing, with readouts expected late next month. It’s further testing the medicine in additional mutations for readouts next year, Meeker said.

In its approved formulation, Imcivree is delivered at a 2mg-starting dose, just below the skin, once daily for two weeks—but the company is already pushing a new-and-improved formulation through the clinic that could make administration easier on patients. Interim phase 2 data recently showed a weekly Imcivree formula was as safe and effective at promoting weight loss as the daily dose, Gregory Gordon, M.D., vice president of clinical at Rhythm, said during 2020’s virtual ObesityWeek event.

The drugmaker’s weekly formula leverages Camarus’ extended-release FluidCrystal injection depot technology, licensed to Rhythm for Imcivree in 2016. Alongside similar safety and efficacy, pharmacological analyses also showed that levels of the drug in patients’ bloodstream were identical throughout treatment with both regimens—plus, when given just once a week, Imcivree levels remained stable throughout the seven-day period, with concentrations falling within the range previously pegged as effective for the daily version.

Editor's note: This story was updated to include information on Rhythm's mid-stage, weekly formulation of Imcivree.