Fact checked byJill Rollet

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March 20, 2024
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Oral medication lowers IGF-1 levels below upper limit of normal for most with acromegaly

Fact checked byJill Rollet
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Key takeaways:

  • The PATHFNDR-2 trial enrolled adults with acromegaly who didn’t previously receive pharmacotherapy.
  • Of the paltusotine group, 56% had an IGF-1 level at or below the upper limit of normal at 24 weeks.

More than half of adults with acromegaly receiving a novel once-daily oral medication achieved an insulin-like growth factor-1 level at or below the upper limit of normal, according to topline results from the PATHFNDR-2 trial.

Paltusotine (Crinetics Pharmaceuticals) is a once-daily oral selectively-targeted somatostatin receptor type 2 agonist. The agent is currently being investigated in phase 3 trials for the treatment of acromegaly. As Healio previously reported, the oral medication met its primary endpoint during the phase 3 PATHFNDR-1 trial, with 83% of adults receiving paltusotine maintaining an insulin-like growth factor-1 (IGF-1) level at or below the upper limit of normal. Participants in PATHFNDR-1 had their acromegaly previously controlled by another medication at baseline.

Acromegaly 2019
Once-daily paltusotine lowered IGF-1 levels below the upper limit of normal for 56% of adults with acromegaly who didn't previously receive pharmacological treatment. Image: Adobe Stock

In PATHFNDR-2, 111 adults with acromegaly who did not previously receive pharmacologic treatment were randomly assigned to receive paltusotine (n = 54) or placebo (n = 57) for 24 weeks, followed by an optional open label extension study. The primary endpoint was the percentage of adults who achieved an IGF-1 level at or below the upper limit of normal.

At 24 weeks, 56% of adults receiving paltusotine had an IGF-1 at or below the upper limit of normal compared with 5% of the placebo group (P < .0001). Adults receiving paltusotine also had a greater reduction in IGF-1 level from baseline to 24 weeks, a higher percentage of participants who achieved an IGF-1 level of 1.3-times or less below the upper limit of normal by the end of the randomized control phase, a greater improvement in self-reported acromegaly symptoms from baseline and a higher proportion of participants who had a growth hormone level of less than 1 ng/mL at the end of the randomized control phase than those receiving placebo.

According to a company press release, paltusotine was well-tolerated. The most common treatment-emergent adverse events with paltusotine were diarrhea, headache, arthralgia and abdominal pain. The proportion of adults with at least one treatment-emergent adverse events were similar in the paltusotine and placebo groups. No serious adverse events occurred for adults receiving paltusotine, according to the release.

“These positive topline results of PATHFNDR-2 are incredibly exciting for both patients with acromegaly and the health care providers who treat them,” 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 release. “This study demonstrates that paltusotine can provide both symptom control as well as biochemical control in patients who are not currently on pharmacologic treatment. If approved, the prospect that paltusotine can offer an innovative, once-daily oral alternative represents a significant step forward in improving the treatment experience for patients.”