Rhythm gets second OK for genetic obesity drug Imcivree, swings into royalty deal – Endpoints News

Another OK, another 2,000 potential patients.

On Thursday, Rhythm Pharmaceuticals received its second FDA green light for its obesity management drug for those with ultra-rare genetic diseases, this time for Bardet-Biedl syndrome, a disease that impacts a number of organs but with early-onset obesity as a major symptom. And the company also engineered a royalty deal netting it up to $100 million.

The FDA approved the drug, known as setmelanotide and marketed as Imcivree, for patients 6 years and up after Phase III data in 31 Bardet-Biedl patients showed it decreased BMI by around 8% compared to placebo. Rhythm chairman and CEO David Meeker noted that while BMI was not a perfect measurement, the company opted to use it over weight because its study included pediatric patients who were still growing.

“Part of the noise in the world of obesity is that [peo­ple say] ‘it’s an epidemic,’ and everybody thinks they understand it, and physicians think they understand it, and a lot of people think it’s a lifestyle choice,” Meeker, former CEO of Genzyme, told Endpoints News.

But while people are slowly understanding obesity is a disease, Rhythm is showing that it’s not one disease, but many diseases, he continued adding that researchers are finding some clear genetic drivers behind obesity.

In November 2020, Rhythm received its first approval for Imcivree for patients with disruptions to their POMC, PCSK1 and LEPR genes. The Bardet-Biedl approval is a bit different, as patients need a clinical diagnosis of the syndrome, which has been linked to 23 different genetic mutations, instead of a gene test confirmation of a specific mutation as they did with the first approval.

Only one minute after announcing the Bardet-Biedl approval, Rhythm disclosed it was entering a royalty deal with the aptly named HealthCare Royalty. As part of the deal, Rhythm will get an initial $37.5 million, followed by an additional $37.5 million pending European approval for Incivree in Bardet-Biedl syndrome and $25 million for certain sales goals. In exchange, Rhythm will pay Healthcare Royalty tiered royalties beginning in the low double digits and falling to the low single digits after certain revenue points on Imcivree’s global sales.

In 2021, Rhythm made a modest $3.2 million from Imcivree sales, though it will likely eclipse that number in 2022, with $1.5 million in sales already in the first quarter.

The money from Healthcare Royalty will keep Rhythm going until the second half of 2024, as it tries to greatly broaden Imcivree’s indication into other diseases that impact the hunger signal pathway upon which it acts. But the FDA doled out a CRL for Imcivree in Alström syndrome, another ultra-rare genetic disease that causes vision and hearing loss, diabetes and obesity, since those patients did not reach the primary endpoint for the study.

In total with its current indications, it can reach some 5,000 patients in the US, Rhythm previously estimated. However, with the studies it has going on now — including a Phase II trial in patients who got treated for a benign brain tumor and come out with extreme hunger, and a Phase III trial looking at 4 additional genes — it could add upwards of 50,000 patient, Meeker estimated.

The drug does come with some side effects though, and five patients discontinued the trial. Most notably, many of the patients experienced skin darkening since Imcivree also hits a pathway that causes melanin release. “It’s like tanning when you go out in the sun … some people note it, some people don’t, and some people like it, and some people are bothered by it,” Meeker said, adding that a few of the patients who discontinued did so due to their skin darkening.

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