Blueprint hits goal in midphase rare disease trial, teeing up pivotal study

Headshot of Marion Dorsch, Blueprint Medicines CSO
Blueprint Medicines CSO Marion Dorsch (Blueprint Medicines)

A phase 2 trial has linked Blueprint Medicines’ avapritinib to statistically significant improvements in the symptoms of patients with indolent systemic mastocytosis (SM). The results tee Blueprint up to move the kinase inhibitor into the pivotal efficacy part of the midphase rare disease clinical trial.

Blueprint won approval for avapritinib in a subpopulation of gastrointestinal stromal tumor (GIST) patients in January. However, at around 8,000 patients, GIST is a small piece of the opportunity facing Blueprint. At around 75,000 patients, SM is a far bigger opportunity than GIST, making it a major part of Blueprint’s plans.

Work to seize that opportunity is advancing on multiple fronts, reflecting the nature of SM. The data shared today come from the first part of a phase 2 trial in patients with non-advanced forms of SM. Those forms, which are known as indolent and smoldering SM, account for around 95% of SM cases.

To test avapritinib in the non-advanced population, Blueprint randomized 39 SM patients to receive one of three doses of the kinase inhibitor or placebo. After 16 weeks, Blueprint assessed the subjects against endpoints including two patient-reported outcome (PRO) tools. One of the PRO tools, the Indolent SM Symptom Assessment Form (ISM-SAF), will be the primary endpoint in the upcoming pivotal trial.

Across the treatment cohorts, the ISM-SAF total symptom score fell by around 30% over the first 16 weeks of the trial. The symptom score in the placebo group fell 3% over the same timeframe. 

Based on the results, Blueprint has chosen to take the 25 mg regimen, the lowest tested dose, into the pivotal trial. The trial linked the 25 mg dose to a 31% fall in the total symptom score. The decline reflects drops of 37%, 25% and 26% respectively in the skin, gastrointestinal and neurological parts of  ISM-SAF.

Blueprint also linked the 25 mg dose to placebo-beating performance against other measures of efficacy. The Mastocytosis Quality of Life scores of patients in the 25 mg cohort fell 34%, on average, underpinned by improvements in symptoms, social life functioning, emotions and skin. The average score in the placebo group rose 7% from baseline.

With Blueprint also tracking declines in serum tryptase, bone marrow mast cells and KIT D816V allele burden, and seeing no serious adverse events in the 25 mg cohort, the data encouraged the biotech to gear up to take avapritinib into part two of the midphase trial. 

Blueprint expects to begin screening patients for the pivotal portion of the phase 2 in June. The trial start joins a series of readouts on Blueprint’s schedule for 2020. Blueprint expects to share top-line data from a trial testing avapritinib in third-line GIST patients in the second quarter, and follow up with results from two studies in advanced SM shortly thereafter.

Under normal circumstances, Blueprint would be expected to share a detailed look at the readouts at in-person medical congresses. That prospect is threatened by the COVID-19 outbreak, but Blueprint’s sharing of results from the indolent and smoldering SM trial shows how researchers can continue to post and discuss data. With COVID-19 forcing the cancellation of the American Academy of Allergy, Asthma & Immunology annual meeting, Blueprint is sharing the data at the group’s virtual forum.