Phase 3 Trial Data Shows Positive Results for Oral Treatment of Acromegaly

  • Apr 2021

Data presented last month at ENDO 2021 from Phase 3 of the MPOWERED study showed that oral octreotide capsules improved clinical symptoms and other patient-reported outcomes compared to long-acting injectable somatostatin receptor ligands (iSRLs) in patients with acromegaly. In addition, oral octreotide capsules met the pre-specified non-inferiority margin compared to long-acting iSRLs in maintenance of biochemical response. Chiasma is marketing the drug as MYCAPPSA.

“The new encouraging data from all five late-breaking poster presentations further expand our understanding of oral octreotide capsules’ potential positive impact for patients with acromegaly who would otherwise need monthly, frequently burdensome SRLs injections,” says Endocrine Society member Maria Fleseriu, MD, FACE, lead investigator of the MPOWERED study, professor of Medicine and Neurological Surgery, director of the Pituitary Center at Oregon Health and Science University in Portland, Oregon, and immediate past president of the Pituitary Society. “As a practicing endocrinologist, I believe that these data provide valuable insights to physicians on the potential benefit of a twice daily oral drug versus long-acting injections for most patients.”

Data highlights from five late-breaking poster presentations at ENDO 2021 are outlined below:

A Phase 3 Large International Noninferiority Trial (MPOWERED): Assessing Maintenance of Response to Oral Octreotide Capsules In Comparison to Injectable Somatostatin Receptor Ligands

  • Data showed that MYCAPSSA demonstrated non-inferiority to iSRLs in maintaining biochemical response, 91% (CI, 80%-97%) of the MYCAPSSA patients maintained insulin-like growth factor 1 (IGF-1) response during the randomized controlled treatment (RCT) phase.
  • MYCAPSSA demonstrated stable IGF-1 levels during the RCT phase comparable to iSRLs, supporting efficacy of MYCAPSSA.

Oral Octreotide Capsules Lowered Incidence and Improved Severity of Acromegaly Symptoms Compared to Injectable Somatostatin Receptor Ligands—Results from the MPOWERED Trial

  • A statistically significant (p = 0.001) reduction from baseline (time of first dose of MYCAPSSA in run-in) was noted in the number of active acromegaly symptoms. Reduction in the number of active symptoms by individual symptom was statistically significant for swelling of extremities (p = 0.01) and fatigue (p = 0.03).
  • The overall mean symptom score decreased from 4.5 to 3.5; the mean change from baseline was statistically significant (p < 0.001) and clinically meaningful (> 1 point reduction is equal to a shift of 1 symptom from severe to moderate, or moderate to mild or resolution of 1 symptom).
  • Overall, 80.4% of the randomized patients maintained or improved their symptoms score during the run-in phase compared to baseline.
  • We believe these findings validate previous results from the open-label, Phase 3 CH-ACM-01 study of MYCAPSSA in which patients switching to MYCAPSSA from iSRLs reported significant reduction in joint pain, extremity swelling and fatigue.

Improved Acromegaly Patient Satisfaction with Oral Octreotide Capsules Compared with Injectable Somatostatin Receptor Ligands in The MPOWERED Trial

  • For the 92 patients randomized, 3 of 5 domains (emotional reaction, treatment convenience, and treatment satisfaction) of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ) showed significant improvement at the end of the run-in (n=37) phase (reflecting outcomes on MYCAPSSA) as compared to baseline (reflecting outcomes on iSRLs). Improvements not reaching statistical significance were also noted for symptom interference and GI interference.
  • Patients receiving MYCAPSSA demonstrated a significant improvement in the Acro-TSQ domain of treatment convenience over the RCT phase in comparison to those receiving iSRLs (p = 0.04).
  • At the end of the RCT phase, breakthrough acromegaly symptoms were reported by 15% of patients in octreotide capsules group and 31% of patients in the iSRLs group.
  • Of note, 47% of patients receiving SRL injections during the RCT phase reported injection site reactions via the Acro-TSQ. 81% of these patients reported that iSLRs interfered with their daily activities.

Addition of Cabergoline to Oral Octreotide Capsules May Improve Biochemical Control in Patients with Acromegaly Who Are Inadequately Controlled with Monotherapy

  • IGF-1 levels improved in most patients over the 36-week study (n=12; 85.7%).
  • Of nine patients with IGF-1 ≥1.3 × ULN at sub-study start, five patients (55.6%; 95% CI, 21.2% -86.3%) exhibited decreases to predefined responder range (<1.3 × ULN) by week 36.
  • Adverse event incidence and nature were similar to the known octreotide safety profile and acromegaly disease burden.
  • For the first time, a study demonstrated the potential benefit of an all-oral combination treatment for acromegaly with avoidance of injection-related burdens.

Safety Results From MPOWERED, A Phase 3 Trial of Oral Octreotide Capsules in Adults with Acromegaly

  • No new or unexpected safety signals were identified during the trial.
  • 39 patients (70.9%) in the MYCAPSSA group and 26 (70.3%) in the iSRL group had ≥1 treatment-emergent adverse events (TEAE). Gastrointestinal AEs were the most common TEAEs within both groups.
  • Safety results were similar between both groups, but the MYCAPSSA group did not have injection site reactions, whereas 24.3% of patients reported injection site reactions as TEAEs from the iSRL group during the RCT phase.

 

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