Agios Pharmaceuticals first made its mark in cancer, but it sold that business in order to focus on rare, genetically defined diseases. That strategy shift is paying off with FDA approval of mitapivat, the first drug that treats a particular rare form of anemia.
Cambridge, Massachusetts-based Agios will market its new product, a twice-daily tablet, under the name “Pyrukynd.” The FDA’s Thursday approval covers use of the drug in adults who have an inherited deficiency of pyruvate kinase, an enzyme that is key to red blood cells. Lacking this enzyme leads to hemolytic anemia, in which the body destroys red blood cells faster than they can be made.
Anemia in PK-deficient patients can be treated with blood transfusions. However, repeated transfusions come with additional complications, including the buildup of iron in the blood. The condition can also lead to gallstones and an enlarged spleen.
Pyrukynd is a small molecule designed to bind to PK enzymes in the body and increase their activity. The FDA based its approval on the results of two Phase 3 clinical trials. The first was a double-blind and placebo-controlled study that evaluated the drug in 80 adults who did not regularly receive blood transfusions. In that 24-week clinical trial, the Agios drug met the main goal of showing a statistically significant increase in hemoglobin.
The additional trial was a 40-week single-arm study that evaluated Pyrukynd in 27 adults who receive regular blood transfusions. The main goal was reducing transfusions compared to the historical transfusion burden of the trial participant. The results showed that 33% of study participants met this goal; in 22% of participants no transfusions were needed over the last 24 weeks of the trial.
The most common side effects reported in tests of Pyrukynd were decreases in estrone and estradiol, which are types of the estrogen hormone, in men; increased urate, which is a type of salt in the body; back pain; and joint stiffness. Investigators could not reliably assess the effects of the Agios drug on estrone and estradiol in women because these hormone levels normally change during the menstrual cycle and with use of hormonal birth control. Pyrukynd’s label cautions that those with liver problems should avoid using the drug.
Agios’s first two FDA-approved products were cancer drugs. Idhifa was approved in 2017 for acute myeloid leukemia characterized by a particular genetic mutation, followed by the 2018 regulatory nod for Tibsovo in the same indication but a different genetic signature. Last April, Agios closed the sale of its oncology business to French pharmaceutical company Servier for $1.8 billion, which the biotech said would enable it to focus on rare genetic diseases. Pyrukynd marks Agios’s first FDA approval under that new strategy.
PK deficiency is rare, and the FDA noted that the condition is likely misdiagnosed or underdiagnosed, making it difficult to determine its prevalence. In an investor presentation, Agios said it estimates 3,000 people have PK deficiency, 80% of them adults and the remaining 20% children. The company also estimates that as many as 70% of PK deficiency patients are undiagnosed. There is no companion diagnostic for Pyrukynd. Speaking on a conference call Friday, Chief Commercial Officer Richa Poddar said that the disease is currently diagnosed with enzyme and genetic testing, and those methods would continue to be used to identify patients eligible for Pyrukynd.
“Since 1961, when the first PKD patient was identified, there has been no treatment options available. Pyrukynd is the first one,” Poddar said. “And that in itself creates a need because you now have a treatment option for these patients to help diagnose even more patients with pyruvate kinase deficiency that were otherwise underdiagnosed.”
Clinical trials are underway testing Pyrukynd in PK-deficient children, which could further expand the market for the drug. Agios also has the opportunity to expand the drug to other indications. Clinical trials are also ongoing in alpha and beta thalassemia, as well as sickle cell disease. In those disorders, Agios could face competition from Forma Therapeutics. That company has reached clinical trials with etavopivat, a small molecule that, like Pyrukynd, is designed to activate PK enzymes.
Agios said the average annual wholesale cost of Pyrukynd is $334,880, before any rebates or discounts. Poddar said the company has pledged to not raise the price for five years. The Agios drug is still under regulatory review in Europe. The company’s drug pipeline includes a next-generation PK activator also in development for various types of anemia.
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