Positive phase III top-line results from CHIASMA OPTIMAL trial of Mycapssa for the maintenance treatment of adults with acromegaly

Chiasma, Inc. announced positive top-line data from the company’s pivotal Phase III CHIASMA OPTIMAL clinical trial evaluating its octreotide capsules product candidate, conditionally trade-named Mycapssa, for the maintenance treatment of adults with acromegaly.

In the CHIASMA OPTIMAL trial, a randomized, double-blind, placebo-controlled, nine-month clinical trial of octreotide capsules conducted under special protocol assessment, or SPA, agreement with the FDA: The primary endpoint was met: 58% of the patients on octreotide capsules maintained their IGF-1 response compared to 19% of the patients on placebo (p = 0.008) . All secondary endpoints were met.

Mycapssa Secondary Efficacy Data : 78% of patients treated with octreotide capsules maintained their growth hormone (GH) levels below 2.5 ng/mL at the end of the core study vs. 30% of patients treated with placebo (p = 0.001). Median time to loss of response (IGF-1 >1.0 × ULN) was not reached (>36 weeks) for patients treated with octreotide capsules vs. 16 weeks for patients treated with placebo (p <0.001). Median time to loss of response (IGF-1 ? 1.3 × ULN) was not reached (>36 weeks) for patients treated with octreotide capsules vs. 16 weeks for patients treated with placebo (p <0.001). 25% of patients treated with octreotide capsules required rescue medication with injectable SSAs (octreotide LAR or lanreotide depot) anytime throughout the study vs. 68% of patients treated with placebo (p =0.003) . Additionally, in a pre-specified exploratory endpoint, mean IGF-1 values across all patients treated with octreotide capsules (including primary endpoint non-responders per protocol), remained within normal limits (? 1.0 x ULN) up to the end of oral treatment. For purposes of this analysis, the end of oral treatment value was the average of week 34 and week 36 values for all patients who completed the study on octreotide capsules and for those patients that required rescue medication, it was their last observed value prior to the use of rescue medication.

Mycapssa Safety and Tolerability : In the CHIASMA OPTIMAL trial, octreotide capsules appeared safe and well tolerated. No new or unexpected safety signals were observed. The overall number of treatment emergent adverse events (TEAEs) was comparable between the octreotide capsules and placebo treatment groups. Two patients on octreotide capsules and one patient on placebo discontinued treatment due to TEAEs. Two patients on octreotide capsules and one patient on placebo had serious adverse events, or SAEs, assessed as not related to study drug. Severe TEAEs as well as TEAEs of special interest (acromegaly symptoms) were more common in placebo treated patients than in patients treated with octreotide capsules.

Comment: Chiasma plans to submit a New Drug Application (NDA) by the end of the year (2019) for octreotide capsules for the maintenance treatment of adults with acromegaly. The CHIASMA OPTIMAL trial was conducted under a SPA agreement with the FDA, which indicates that the FDA agreed the design and planned analysis of the CHIASMA OPTIMAL results adequately address the objectives necessary to support a regulatory submission.