Blueprint met all its endpoints in bid for expanded Ayvakit label — but stock trends lower anyway
Blueprint Medicines announced this morning that the second part of its study on Ayvakit in non-advanced systemic mastocytosis (SM) — a rare disease in which a type of white blood cells known as mast cells builds up — met all endpoints, but the biopharma left key questions unanswered.
In 212 patients, with 141 in the treatment arm and 71 in the control arm, patients who got Ayvakit saw an average 15.6-point decrease in their symptom scores compared to a 9.2-point decrease in the placebo arm at 24 weeks. In an extension study, those on Ayvakit saw their symptom scores drop by 20.2 points by week 48.
Later this year, the Massachusetts biotech plans to file for a supplementary approval for Ayvakit, which was greenlit for the rarer advanced form of SM back in 2021.
Despite the apparent positive readout, Blueprint $BPMC was trading down by over 20% this morning, dropping from around $68 to $54.
For one, analysts noted that the difference between the average symptom scores of the treatment and placebo arms in the Part 2 results was just over 6 points, substantially less than the 16-point difference in the smaller Part 1 study. Not only did the treatment have a smaller effect in Part 2 than in Part 1, in which patients saw a 19-point improvement in their symptom scores, but the placebo plus standard of care fared considerably better than in Part 1 as well, where the control arm saw only a 3-point improvement in symptom scores.
When asked about the difference in the control arm, Blueprint COO Christy Rossi told Endpoints News that it was “hard to speculate,” but noted the multi-center, global scale of the second part of the study.
In addition, Blueprint didn’t share exact numbers on a key secondary endpoint — responder rate — leaving the question of how many patients the treatment worked for on the table, though it did reach statistical significance here. Rossi maintained that Blueprint would include that data in a future conference presentation.
The responder rate, or the proportion of patients with a ≥30% decrease in total symptom score, was initially the primary endpoint of the study, but following discussions with the FDA, Blueprint swapped its primary and secondary endpoints for the study.
In addition, when asked about price during the investor call, Blueprint chief commercial officer Philina Lee didn’t go into specifics, saying, “As we get closer to a potential launch, we will continue to engage with providers and payers and other stakeholders, and we will use all of these inputs to inform our ultimate pricing approach.”
All of these issues lead up to one major question: Will the expanded label into non-advanced SM make Blueprint profitable?
Ayvakit, Blueprint’s longtime lead drug, was first approved for a very specific form of intestinal cancer in 2020. At the time, the biopharma priced Ayvakit at $32,000 a month, a price point that was twice what analysts anticipated, as well as one it maintained when Ayvakit was approved for advanced SM. Last year, Ayvakit made $53 million, while Blueprint functioned at a loss of $644 million. In the first half of this year, Blueprint has made $52 million, and expects Ayvakit sales revenue to jump to $115 to $130 million for 2022.
While SVB Securities analysts described the non-advanced SM data as “approvable,” they noted:
In our view, these data will further magnify the commercial debate, as investors question the size of the addressable ISM population for a chronically used therapy with a limited treatment effect that could cost >$350,000 per year. We think some physicians, payors and patients may balk at the anticipated cost given that Ayvakit appears to add about a 10% improvement in symptoms versus best supportive care.
The analysts also added that Blueprint’s data Wednesday “opens the door for competition” from the likes of Cogent Biosciences, “while largely de-risking the concerns about a large placebo effect causing the trial to fail.” Cogent has a readout for its drug bezuclastinib in non-advanced SM slated for early next year, and its stock $COGT was trading up 18% Wednesday morning.