Blueprint CEO touts Ayvakit's rare disease win, but analysts flag looming 'commercial debate'

An Ayvakit trial win in the rare blood disorder of indolent systemic mastocytosis could be an inflection point for Blueprint Medicines’ commercial business. The company now has positive trial data to support that expansion, but analysts say the debate around the drug’s sales potential is just starting.

In trial results released Wednesday, Blueprint’s Ayvakit topped placebo in helping patients with non-advanced systemic mastocytosis (SM) relieve symptoms in terms of mean change in a specially designed total symptom score.

During a conference call, Blueprint CEO Kate Haviland touted the data’s “breadth and consistency,” adding that the trial showed “highly significant” improvements for the KIT inhibitor across the primary and all key secondary endpoints. Mariana Castells, M.D., Ph.D., director of Brigham and Women’s Hospital’s mastocytosis center and an investigator in the trial, said the drug “will make a tangible difference” and will “transform” the quality of life for patients.

But in a Wednesday note, SVB Securities analysts, led by Andrew Berens, M.D., suggested that while the data should enable an FDA approval, they’ll also “further magnify the commercial debate.” Other analysts on Wednesday’s call also questioned the magnitude of Ayvakit’s benefit. And investors sent Blueprint’s share price down by 23% in trading Wednesday.

On the total symptom score, Ayvakit patients enjoyed an average 15.6-point improvement from baseline at 24 weeks, bigger than the 9.2-point reduction in the control arm, translating into a difference of 6.4 points.

But as Berens noted, the new data marked a slump from part 1 of the Pioneer trial. In that first part, the difference in score change between the two arms was 16.5 points: Ayvakit patients recorded a 19.7-point improvement versus 3.2 points for placebo.

The 6.4-point difference came below the 7 to 10 points industry watchers had hoped for, a Raymond James analyst pointed out during the call. In response to the weaker showing in part 2, Blueprint’s chief medical officer Becker Hewes, M.D., noted that patients who rolled over to an open-label extension study experienced a symptom reduction widening to 20.2 points at 48 weeks. The company didn’t disclose how the control arm performed at that time point.

The trial includes patients with moderate to severe disease and those with or without steroid use, Hewes said, suggesting Ayvakit could be used in different patient populations.

As for whether a 6.4-point improvement is approvable, Hewes said, “the FDA has been very clear that the way to determine clinical significance is to look at the totality of the data,” rather than average change in total symptom score alone.

Ayvakit also triggered a response in more patients than placebo did as determined by an at-least-30% reduction in the total symptom score. That was originally the trial’s primary endpoint until the FDA asked to replace it. Blueprint didn’t disclose detailed data for secondary endpoints, saying it will present them at an upcoming medical meeting.

The Blueprint med also showed a favorable safety profile. Serious side effects occurred in 5% of Ayvakit patients versus 11.3% in the control arm. 

Ayvakit is currently approved in advanced SM, which only accounts for 5% to 10% of total SM patients. The non-advanced SM population is much larger, and with the latest Pioneer trial readout, Blueprint is targeting about 7,500 non-advanced patients with moderate to severe disease who are currently seeking treatment.

Before Wednesday’s readout, SVB analysts predicted Blueprint’s KIT inhibitor franchise could reach $1.34 billion in the U.S. and EU non-advanced SM markets, versus $486 million for advanced disease.