A Sickle Cell Trial Delivers Mixed Results. Agios Stock Falls by 48%.

(Dreamstime)

Key Points

• Agios Pharmaceuticals’ Pyrukynd trial for sickle cell disease met its primary goal of increasing hemoglobin but showed no significant reduction in pain crises or fatigue.
• Agios shares dropped 48% following the mixed trial results, but the company still plans to seek FDA approval for Pyrukynd in sickle cell patients.
• The trial showed 40.6% of patients on Pyrukynd achieved a hemoglobin response versus 2.9% on placebo, but a 14% reduction in pain crises was not statistically significant.

For weeks, biotech investors have been bracing for the results of a large, late-stage trial of Agios Pharmaceuticals’ Pyrukynd pill in patients with sickle cell disease.

Pyrukynd is already approved as a treatment for a less common blood disorder, but sickle cell disease is a widespread, serious condition with limited treatment options most common in Black and African-American people in the U.S., and a successful trial would unlock a major market for Agios.

Last week, Cantor Fitzgerald analyst Eric Schmidt called the readout “one of the biggest remaining events in the biotech industry” this year.

Agios reported the results of the study on Wednesday, and they were mixed. The trial met its goal of increasing the concentration of hemoglobin in patients’ blood. But the difference in the number of annual pain crises caused by sickle disease wasn’t significantly lower in patients who received the drug. Fatigue wasn’t significantly better in patients on the drug, either.

In other words, the drug looked like it should be working, but most patients didn’t experience much of a difference.

Agios shares were down 48% in Wednesday trading, at $23.50. The company says that it still intends to ask the Food and Drug Administration to approve the drug for sickle cell patients, despite the lack of a statistically significant improvement in clinical outcomes.

“With the current product profile, we actually see a very compelling commercial opportunity,” Agios’ chief medical officer and head of R&D, Sarah Gheuens, said on an investor call early Wednesday. “Of course we will need to engage with the FDA…but the opportunity continues to be very, very compelling for us.”

The company also said it planned to cut costs. “We will take proactive steps to reduce our operating expenses to extend our cash runway,” Agios CEO Brian Goff said on the call. The company had $1.3 billion in cash on hand at the end of the third quarter.

The Food and Drug Administration first approved Agios’ Pyrukynd in 2022 as a treatment for hemolytic anemia in patients with a rare genetic disorder called pyruvate kinase deficiency, and is expected to decide next month whether to approve the drug as a treatment for another blood disorder called thalassemia.

Approval in sickle cell disease, however, would be transformative for the company, which has no other approved products aside from Pyrukynd. Schmidt wrote in his note earlier this year that of the $2.4 billion in 2035 sales he estimates for the drug, $1.6 billion would come from the sickle cell indication.

Sickle cell disease is a genetic blood disorder that results in malformed hemoglobin cells, which can cause episodes of extreme pain that may result in hospitalization. Treatments are limited, and they grew more limited last year, when Pfizer withdrew a sickle cell treatment called Oxbryta from the market amid safety concerns.

The Pyrukynd sickle cell trial enrolled roughly 200 people. After a year, 40.6% of the patients on the drug had achieved a hemoglobin response, meaning there was higher concentration of hemoglobin in their blood, compared with 2.9% on a placebo.

The second key measure of the trial, however, was the annualized rate of sickle cell pain crises. For patients on placebo, the rate was 3.05 crises a year, compared with 2.62 crises for patients who received the drug. The company said that the 14% reduction wasn’t statistically significant, though it noted there was a “trend favoring” the drug.

On a measure of fatigue called Promis Fatigue 13a, there was no statistically significant difference in the change in the score between patients on a placebo and those who received the drug.

The company said that among those patients on Pyrukyund whose hemoglobin concentration improved, there was a lower annualized rate of pain crises.

The question now is what the FDA will make of the Pyrukyund data.

“The unmet need in [sickle cell disease] is enormous, and the FDA may well show flexibility,” Schmidt wrote in a Wednesday note.

Write to Josh Nathan-Kazis at josh.nathan-kazis@barrons.com