Oral acromegaly agent reduces IGF-1 levels below upper limit of normal for most adults
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More than 80% of adults with acromegaly achieved an insulin-like growth factor level at or below the upper limit of normal at 36 weeks with an investigational once-daily oral medication, according to topline results from a phase 3 trial.
Paltusotine (Crinetics Pharmaceuticals) is an oral selectively targeted somatostatin receptor type 2 agonist developed to treat acromegaly and neuroendocrine tumors. According to a company press release, the agent met its primary endpoint and all secondary endpoints in the phase 3 PATHFNDR-1 trial, a randomized, double-blind trial in which adults with acromegaly were randomly assigned to receive once-daily paltusotine (n = 30) or placebo (n = 28) for 36 weeks. The study population included adults with acromegaly biochemically controlled with either octreotide (Mycapssa, Chiasma) or lanreotide (Somatuline Depot, Ipsen) monotherapy.
At 36 weeks, 83% of adults receiving paltusotine maintained an IGF-1 level at or below the upper limit of normal compared with 4% of the placebo group (P < .0001). The paltusotine group also had a smaller change in IGF-1 level compared with placebo (P < .0001). Adults receiving paltusotine had a decline in Acromegaly Symptoms Diary total score of 0.6 points from baseline to 36 weeks compared with a total score increase of 4.6 points for the placebo group (P = .02). The percentage of adults maintaining a growth hormone level of less than 1 ng/mL was 87% in the paltusotine group compared with 28% in the placebo group (P = .0003).
There were no serious or severe adverse events reported for adults receiving paltusotine, and the agent had a similar percentage of adults reporting a treatment-emergent adverse event as placebo. The proportion of participants reporting an acromegaly-related adverse event was lower in the paltusotine group compared with placebo (30% vs. 86%).
“The results of PATHFNDR-1 are relevant to the patients we see every day in clinical practice who are biochemically controlled on standard of care injections,” Monica R. Gadelha, MD, PhD, professor of endocrinology at the Medical School of the Universidade Federal do Rio de Janeiro and a principal investigator in the PATHFNDR program, said in the press release. “My colleagues and I are increasingly convinced many patients would appreciate an oral alternative, which confers similar benefits without the burden and discomfort of the injections. This study demonstrated that the transition to paltusotine was done seamlessly, and the results showed once-daily, oral paltusotine maintained both symptom control as well as biochemical control when switching from monthly injections.”
Full results from PATHFNDR-1 are expected to be presented at upcoming scientific conferences, according to the release.
A second phase 3 study, PATHFNDR-2, is underway to evaluate paltusotine for adults with acromegaly who are treatment naive or not receiving medical therapy. Topline data from PATHFNDR-2 is expected to be available in the first quarter of 2024. Another open-label phase 2 study is being conducted to evaluate paltusotine for adults with carcinoid syndrome, with preliminary results expected later in 2023. In the release, Crinetics Pharmaceuticals said it plans to submit a new drug application to the FDA in 2024 for regulatory approval of paltusotine for all people with acromegaly who require pharmacotherapy.
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