The Endocrine Society

The Endocrine Society

Source:

Samson SL, et al. OR14-3. Presented at: ENDO annual meeting; March 20-23, 2021 (virtual meeting).

Disclosures: Chiasma funded this study. Samson reports she is a research investigator for Chiasma, Corcept, Novartis and OPKO Health. Please see the meeting abstract for all other authors’ relevant financial disclosures.
April 08, 2021
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Oral octreotide provides sustained biochemical control in acromegaly

Source:

Samson SL, et al. OR14-3. Presented at: ENDO annual meeting; March 20-23, 2021 (virtual meeting).

Disclosures: Chiasma funded this study. Samson reports she is a research investigator for Chiasma, Corcept, Novartis and OPKO Health. Please see the meeting abstract for all other authors’ relevant financial disclosures.
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Adults with acromegaly who responded to treatment with an oral form of the somatostatin analogue octreotide maintained response for an additional 48 weeks with no new safety signals observed, data from an open-label extension study show.

Susan L. Samson

“These findings support that the effects of oral octreotide capsules (Mycapssa, Chiasma) on insulin-like growth factor I levels are sustained and can control IGF-I in the long term,” Endocrine Today Editorial Board Member Susan L. Samson, MD, PhD, FRCPC, FACE, senior associate consultant in endocrinology and neurosurgery at Mayo Clinic in Jacksonville, Florida, told Healio. “Importantly, this helps to emphasize that oral octreotide capsules are an effective and welcome addition to our armamentarium of treatments for our patients with acromegaly, allowing us to take a personalized medicine approach.”

Acromegaly 2019
Source: Adobe Stock

Samson and colleagues analyzed data from 40 participants with acromegaly (20 from the original oral octreotide arm and 20 from the placebo arm) who enrolled in an open-label extension of CHIASMA OPTIMAL, a double-blind placebo-controlled trial with oral octreotide therapy. Within the trial cohort, 90% of participants enrolled in the open-label extension. For the extension phase, all participants initially received a 60 mg daily dose of oral octreotide, titrated up (80 mg) or down (40 mg) based on IGF-I level or based on acromegaly signs or symptoms. Trial endpoints for the open-label extension were exploratory and included the proportion of patients who completed week 48 of the extension, the proportion who completed as responders, defined as average IGF-I level less than 1 time the upper limit of normal at weeks 46 to 48, and changes in IGF-I from baseline. The findings were presented virtually at the ENDO annual meeting.

At the end of the open-label extension, three participants were receiving a 40 mg dose, 10 were receiving a 60 mg dose and 27 were receiving an 80 mg dose.

Sustained response with treatment

Researchers observed that 90% of participants who initially received octreotide (n = 18) and 70% of participants who initially received placebo (n = 14) during CHIASMA OPTIMAL completed the open-label extension study.

All participants who initially received octreotide and were considered responders to therapy at the end of the placebo-controlled trial (n = 14) completed the open-label extension, with 92.6% maintaining response at week 48. For participants who received oral octreotide during the placebo-controlled trial, average IGF-I level during the extension phase was 0.91 and 0.9 times the upper limit of normal at baseline and week 48, respectively, emphasizing the maintenance of control. The mean change in IGF-I level from baseline for the placebo-controlled trial through week 48 of the open-label extension was 0.06 times the upper limit of normal for participants who received oral octreotide for both phases of the study.

Among participants who received placebo and were considered responders at the end of the placebo-controlled trial (n = 5), all maintained response at week 48 of the extension phase after switching to oral octreotide therapy. Among patients from the placebo group who completed the placebo-controlled trial and did not revert to prior injectable therapy (n = 9), the average IGF-I values were 1.09 and 0.87 times the upper limit of normal at baseline and week 48, respectively.

Samson said the most common treatment-emergent adverse events were gastrointestinal; most were mild or moderate.

“Along with the data mentioned ... the safety data also reveals some interesting findings,” Samson told Healio. “No new safety concerns were found with longer-term use. Further, the clinical trials start patients at 40 mg, or 20 mg twice daily, which is the current label approved by the FDA; however, the extension was unique in that patients started at 60 mg per day instead of 40 mg. That means that patients entering from the placebo arm were drug-naive when starting on the higher dose of 60 mg.”

Optimal starting dose

Samson noted that there was a decrease in the rate of treatment-emergent adverse events, from 96.4% in the placebo-controlled trial in the oral octreotide arm (starting dose, 40 mg) and 57.9% for those entering the extension from the placebo arm (starting dose, 60 mg), and the rate of treatment-related adverse event also was lower, at 53.6% vs. 31.6% for both groups, so that there were fewer adverse events recorded for participants starting at the higher dose.

During a Q&A session after the presentation, Samson, responding to a question about the optimal starting dose, said data from the extension study provided investigators with a better picture of how patients tolerate a starting dose of 60 mg for oral octreotide.

“The 60 mg starting dose in the open-label extension, for those who had previously been [assigned] placebo, does let us look a little more closely at how that dose works and how patients do, safety-wise,” Samson said. “We know that treatment-emergent adverse events and treatment-related adverse events [in the placebo-controlled trial] were lower. It makes you look back at the original trial and think about the adverse events we saw in placebo vs. oral octreotide — things like the symptoms of acromegaly that can worsen during the course of a trial that are still recorded as an adverse event. Knowing those [events] are lower in oral octreotide in the placebo-controlled trial, and doing a deeper dive into safety data for this open-label extension study, will surely answer that question.”

As Healio previously reported, the FDA approved octreotide in June as long-term maintenance therapy for people with acromegaly who have responded to and tolerated treatment with octreotide injection or lanreotide (Somatuline Depot, Ipsen). It is the first and currently the only oral somatostatin analogue approved by the FDA.