As Rhythm Pharmaceuticals preps for first approval, CEO hits the exit

FDA Building 2
As Rhythm Pharmaceuticals' drug is set to be reviewed this year by the FDA, its longtime CEO is set to leave the biotech. (FDA)

Fierce 15 winner Rhythm Pharmaceuticals is on the cusp of gaining its first approval in 2020, but it will be ushering in this potential milestone without its chief.

The Boston biotech, which last year saw positive results for its late-stage genetic obesity drug setmelanotide, said after-hours Monday that Keith Gottesdiener, M.D., “intends to step down” as CEO, president and board member.

He will stay on until the company’s rolling submission to the FDA is complete; a successor is now being sought. This comes as the biotech preps for the major transition from a small startup to a commercial biotech, and clearly it wants a leader with that shift in mind.

Back in August, several phase 3 trials of Rhythm’s setmelanotide in patients with genetic obesity hit their primary endpoints, teeing them up for a rolling NDA with the FDA.

The two clinical trials investigated the melanocortin-4 receptor agonist in patients with pro-opiomelanocortin (POMC) or leptin receptor (LEPR) deficiency obesity. The POMC and LEPR trials enrolled 10 and 11 patients, respectively, and assessed the effect of one year of once-daily subcutaneous setmelanotide injections on their weight and hunger.

Eight of the 10 patients enrolled in the POMC trial experienced a reduction in body weight of 10% or more, resulting in the trial hitting its primary endpoint with a p-value of less than 0.0001. Among the participants who hit a weight loss threshold after 12 weeks, the mean reduction in body weight over the course of the trial was 25.4%. Rhythm reported a 27.8% drop in hunger in those participants.

The LEPR trial recorded smaller but still statistically significant changes. Five of the 11 subjects in the LEPR trial experienced a 10% or more reduction in body weight. The average weight loss across the course of the trial was 12.5%.

As a single-arm, open-label trial, the study lacked a comparator to show how patients would have performed without setmelanotide. Rhythm offset that shortcoming by including a four-week placebo withdrawal period. During this period, subjects “almost immediately gained weight,” according to Rhythm, and had on average gained more than 11 pounds by the end of their time on placebo.

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“On behalf of the entire Board of Directors, I want to thank Keith for his significant contributions to Rhythm,” said David Meeker, M.D., chairman of the board. “As Rhythm prepares to enter its next chapter as a commercial company, now is an appropriate time to initiate this transition. We believe Rhythm has a strong management team, is well capitalized, and all of its major milestones are on track, including the planned submission of our first NDA to the FDA. We are confident this will be a smooth transition as we work to identify the next leader for Rhythm and continue to execute on our mission of transforming the standard of care for people with rare genetic disorders of obesity.”

“For the more than eight years that I have been CEO, it has been an honor to lead the talented Rhythm team, and I am immensely proud of our work to advance setmelanotide and bolster the understanding of rare genetic disorders of obesity,” added Gottesdiener.

“With the completion of our first phase 3 trials and our pending NDA submission, it is a natural time for me to pass the baton and for Rhythm to welcome new leadership. I am confident that Rhythm is in an excellent position to deliver on the potential of setmelanotide, and I look forward to working with the Board and leadership team over the next several months to ensure a smooth transition.”

If Rhythm can gain approval this year (and the submission should be done by the first quarter), attention will turn to the question of the market opportunity for the drug. A National Institutes of Health analysis of the medical literature found around 50 reported cases of POMC deficiency. The prevalence of LEPR deficiency is unknown, leaving scope to doubt whether setmelanotide will be a significant drug commercially even if it makes it to market. A key question will also be how it decides to price its drug, should it gain approval, in an election year when high price tags are gaining more and more attention.

There are, however, other opportunities for the drug, including top-line data from that are slated from its phase 3 in Bardet-Biedl and Alström syndromes within the next year.

Rhythm said it “is well capitalized” and believes it has sufficient resources to fund its operations through at least the end of 2021.