Positive response to oral octreotide seen for adults with acromegaly across three trials
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Key takeaways:
- Most adults with acromegaly maintained or improved IGF-I levels with oral octreotide in three phase 3 trials.
- Fewer adults reported moderate or severe joint pain and swelling at 6 months compared with baseline.
BOSTON — The majority of people with acromegaly receiving oral octreotide achieve a biochemical response, regardless of their baseline insulin-like growth factor I level, according to data from a post hoc analysis.
As Healio previously reported, oral octreotide (Mycapssa, Chiasma) was approved by the FDA in 2020 as a long-term maintenance therapy for people with acromegaly who previously responded to an injectable somatostatin receptor ligand. At ENDO 2024, researchers presented a pooled analysis of the CH-ACM-01, OPTIMAL and MPOWERED phase 3 trials to further explore key points on biochemical response maintenance and predictors of response, according to Maria Fleseriu, MD, FACE, professor of medicine and neurological surgery and director of the Oregon Health & Science University Pituitary Center and a Healio | Endocrine Today Co-editor.
“Oral octreotide has a comprehensive set of phase 3 studies that, when pooled, confirms the overall maintenance of biochemical control in the studied population with a potential for improvements on measures of symptom control,” Fleseriu told Healio. “Tolerability of the drug was consistent with the safety profile of the somatostatin receptor ligand class with gastrointestinal-related events being the most common, albeit largely transient in nature.”
The pooled analysis included 318 adults aged 18 years and older with acromegaly who responded to injectable somatostatin receptor ligand therapy before initiating oral octreotide (mean age, 54 years; 59.4% women). Researchers analyzed data from the dose escalation and core treatment phases of CH-ACM-01, the double-blind, placebo-controlled phase of OPTIMAL and the run-in phase of MPOWERED. Maintenance and improvement of IGF-I levels were assessed according to baseline IGF-I.
“Each of the studies were unique in design, but across all, patients received 6 months or more of oral octreotide with a large majority starting therapy at the time of the next scheduled injection,” Fleseriu said. “Dose titration was performed similarly across all studies based on biochemical and symptom measures. Biochemical criteria for enrollment and assessment of outcomes was the same for each individual study, but the definition of response was defined differently across all three. In two of the three studies, symptoms were collected as an outcome. In the third, OPTIMAL, they were only recorded as an adverse event of special interest.”
Most respond to oral octreotide
Oral octreotide maintained or improved IGF-I levels for most adults in all baseline IGF-I categories. Among 214 adults with an IGF-I at or less than one time the upper limit of normal, 72% maintained their IGF-I level. Of 81 adults with a baseline IGF-I level more than one time but less than 1.3 times the upper limit of normal, 44% maintained their IGF-I level with oral octreotide and 20% improved their level to one time or less the upper limit of normal. For 23 adults with an IGF-I level 1.3 times the upper limit of normal or higher at baseline, 65% maintained their level, 30% reduced their level more than one time and less than 1.3 times the upper limit of normal and 4% had an IGF-I reduction to one time or less the upper limit of normal.
IGF-I change was similar across all three baseline IGF-I groups. Response to oral octreotide rates were also similar between adults who previously received a low, moderate or high injectable somatostatin receptor ligand dose.
“For a long-term treatment, maintenance of control is as important as achieving initial control,” Fleseriu said. “The majority of patients maintained biochemical control, and when we specifically look at the group with a [baseline] IGF-I one time or less the upper limit of normal, 72% achieved that target. One interesting point — 14% of this group were technically allowed to have IGF-I levels up to 1.3 times the upper limit of normal, as we have recognized that variability of IGF-I could be 20%.”
Change in symptoms
Among 134 responders to oral octreotide, the percentage reporting moderate or severe joint pain dropped from 36% at baseline to 22% at 6 months (P = .0001), and the proportion reporting swelling declined from 15% at baseline to 10% at 6 months (P = .018). Of 194 oral octreotide responders who had symptom data available, 56% reported one symptom or less at baseline, 32% had two symptoms and 20% reported three symptoms. At 6 months, 39% of the group had one or fewer symptoms, 20% reported two symptoms and 12% reported three symptoms.
Of the study group, 45.3% reported at least one gastrointestinal event with a median time to onset of 22.5 days. The median duration of an event was 14 days, and 6.4% discontinued their trial due to a gastrointestinal-related adverse event. Gastrointestinal medical history was reported by 50.5% of adults in the analysis.
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Fleseriu M, et al. MON-124. Presented at: ENDO annual meeting; June 1-4, 2024; Boston.
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