Agios Pharmaceuticals started out in cancer but sold the business in order to focus on rare genetically defined diseases.This strategic shift is paying off FDA Approval for Mitapivathe first special rare form of the drug to treat anemia.
Cambridge, Massachusetts-based Agios will market its new product under the name “Pyrukynd,” a twice-daily tablet. Thursday’s FDA approval covers the drug’s use in adults with a genetic defect in pyruvate kinase, a key enzyme in red blood cells. A lack of this enzyme can lead to hemolytic anemia, in which the body destroys red blood cells faster than they can be made.
Anemia in patients with PK deficiency can be treated with blood transfusions. However, repeated blood transfusions can bring additional complications, including a 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 and increase the activity of PK enzymes in the body. FDA approval is based on results from two Phase 3 clinical trials. The first was a double-blind and placebo-controlled study evaluating the drug in 80 adults who did not receive regular blood transfusions. In a 24-week clinical trial, the Agios drug met its primary goal of showing a significant increase in hemoglobin.
The other trial was a 40-week, single-arm study evaluating Pyrukynd in 27 adults receiving regular blood transfusions. The primary goal was to reduce blood transfusions compared to the historical transfusion burden of trial participants. Results showed that 33 percent of study participants achieved this goal; 22 percent of participants did not require blood transfusions during the final 24 weeks of the trial.
The most common side effects reported in the Pyrukynd test were reductions in estrone and estradiol, a type of estrogen, in men. Increased urate, a type of salt in the body; back pain; and joint stiffness. The researchers were unable to reliably assess the effects of the Agios drug on estrone and estradiol in women because these hormone levels typically change during the menstrual cycle and when using hormonal contraception. The label for Pyrukynd warns that those with liver problems should avoid the drug.
Agios’ first two FDA-approved products are cancer drugs. Idhifa was approved in 2017 for acute myeloid leukemia characterized by specific genetic mutations, followed by a regulatory nod to Tibsovo in 2018 for the same indication but with a different genetic profile.In April last year, the discount closure The $1.8 billion sale of its oncology business to French drugmaker Servier, the biotech said, would allow it to focus on rare genetic diseases. Pyrukynd marks the first FDA approval for Agios under this new strategy.
PK deficiency is rare, and the FDA notes that the disorder may be misdiagnosed or underdiagnosed, making it difficult to determine its prevalence. In an investor presentation, Agios said an estimated 3,000 people have PK deficiency, 80% of whom are adults and the remaining 20% are children. The company also estimates that as many as 70% of people with PK deficiency go undiagnosed. Pyrukynd has no companion diagnostics. The disease is currently diagnosed with enzymatic and genetic tests, and those methods will continue to be used to identify patients eligible for Pyrukynd, Chief Commercial Officer Richa Podar said on a conference call Friday.
“Since the first patient with PKD was discovered in 1961, there has been no treatment option available. Pyrukynd was the first,” Poddar said. “That in itself creates a need because you can now provide these patients with a treatment option to help diagnose more patients with pyruvate kinase deficiency that would otherwise be underdiagnosed.”
Clinical trials are underway to test Pyrukynd in children with PK deficiency, which could further expand the drug’s market. Agios also has an opportunity to expand the drug into other indications. Clinical trials for alpha and beta thalassemia and sickle cell disease are also underway. In these diseases, Agios could face competition from Forma Therapeutics. The company is already in clinical trials with etavopivat, a small molecule designed to activate PK enzymes like Pyrukynd.
Agios said the average annual wholesale cost of Pyrukynd is $334,880, excluding any rebates or discounts. Poddar said the company has pledged not to raise prices for five years. The Agios drug is still under regulatory review in Europe. The company’s drug pipeline includes next-generation PK activators that are also in development for various types of anemia.
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