Blueprint drug succeeds in rare disease study important to its market prospects

Dive Brief:

• A drug developed by Blueprint Medicines helped reduce symptoms of patients with a slow-moving, early form of the rare disease systemic mastocytosis in a Phase 2 trial, positioning the company to ask for regulatory approval later this year.
• Patients who received Blueprint’s drug Ayvakit and supportive treatment experienced a meaningful reduction in symptoms after six months, compared to a placebo and additional care. Study participants who received Ayvakit had scores on a test measuring those symptoms decline by about 16 points, while placebo patients’ scores fell by roughly nine points after six months.
• Ayvakit met all of the study’s secondary goals as well, and both mild and serious side effects were more common in the control group. Blueprint said the results will support an application to expand the drug’s use beyond the much smaller number of patients with advanced disease, for whom it was initially approved last June. But shares fell more than 20% as analysts questioned the magnitude of the drug’s benefit as well as its commercial prospects. 

Dive Insight:

Over the past two years, Blueprint brought its first two drugs to market — Ayvakit and a cancer drug called Gavreto — and has since expanded use of each through secondary approvals.

The company has said it plans to stay independent and is taking steps towards that goal, including making its first acquisition last year and, more recently, shoring up its cash reserves through two creative financing transactions.

But Blueprint still isn’t making money. The company recorded a net loss of $644 million last year and lost another $265 million through the first half of 2022. Gavreto sales to date suggest the drug’s launch isn’t yet profitable, SVB Securities analyst Andrew Berens wrote in a note earlier this month. Ayvakit, meanwhile, generated about $53 million in net revenue in 2021.

Amid a sector-wide downturn, shares in the company have lost nearly 40% of their value this year.

An approval of Ayvakit in ISM — a condition characterized by the abnormal proliferation of mast cells in certain organs — could help lift the company. Blueprint estimates 90% to 95% of the roughly 32,000 systemic mastocytosis patients in the U.S. have the indolent form, or ISM, for which there are no approved medicines capable of changing the disease’s course. Berens projects Ayvakit, if approved for ISM, could generate $1.3 billion in peak yearly sales from that indication alone.

Ayvakit’s goal in the Phase 2 trial was to outperform placebo at alleviating the constellation of unpredictable, but potentially severe, symptoms of ISM, among them pain, brain fog and abdominal issues. Treatment succeeded on that measure, as symptom scores fell by about 16 after 24 weeks and by 20 points after 48 weeks. At the start of the trial, patient scores were on average about 50 points.

The drug also hit six secondary objectives, such as reducing levels of mast cells in the bone marrow and relieving patients’ most severe single symptom.

According to Blueprint, serious side effects were more than twice as common in the placebo group (11%) than among those who received Ayvakit (5%). There were no instances of intracranial bleeding events, which had been a concern with the drug. Nausea and headache were more frequent among placebo recipients, while peripheral edema occurred more commonly among those receiving Ayvakit.

Blueprint could still face commercial challenges if Ayvakit is approved in ISM. The drug costs more than $300,000 per year in advanced disease, a life-threatening condition. Indolent disease, by comparison, is “predominantly life-altering,” Berens wrote, which is why investors surveyed by SVB expect the company to face “increased commercial scrutiny by payers and providers.”

Wall Street analysts also questioned the magnitude of the drug’s benefit. Stifel analyst Bradley Canino noted the results were below investors’ high expectations and may not be strong enough to end the commercial debate. Christopher Raymond, of Piper Sandler, added that the roughly 31% reduction in symptom scores Blueprint reported “barely” cleared the 30% threshold for clinical significance set by the company and outside experts. 

”We think it may be an uphill battle for [Ayvakit] to see broad adoption in ISM patients,” particularly if it’s given the same price it has in advanced disease, Raymond wrote. “The door remains wide open for a better mousetrap.”

Shares of Cogent Biosciences, which is developing a rival ISM drug that’s in Phase 2 testing, climbed as high as 16%.

In an email, Blueprint spokesperson Andrew Law said that, while it’s premature to discuss pricing in ISM, “in the coming months we plan to engage with healthcare providers and payers to share the data and get input on our strategy.”

Editor’s note: This story has been updated to reflect company stock prices Wednesday morning and to include commentary from analysts.  

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