Cancer drugmaker Agios offers promising data from two studies testing blood disorder drug
With two cancer drugs on the market, the spotlight is on Agios’ rare metabolic disease franchise led by mitapivat, its experimental drug under development for a range of conditions including pyruvate kinase deficiency, thalassemia, and sickle cell disease.
At the European Hematology Association Annual Congress (EHA), the company issued two updates on the effect of mitapivat — a drug designed to target pyruvate kinase-R (PKR), an enzyme involved in the conversion of sugar, or glucose, into energy that is critical for the survival of red blood cells.
The first update came from an ongoing mid-stage study testing the drug in two forms of thalassemia, an inherited blood disorder. In the study, 12 out of 13 patients saw statistically significant improvements in hemoglobin concentration, setting the stage for a pivotal trial next year.
The trial, which has so far enrolled 20 patients, is evaluating the effect of the drug in more moderate forms of the disease, in patients that are not dependent on blood transfusions. Patients started on a lower 50 gm dose and then were gradually given the higher 100 mg dose.
Thalassemia, caused by mutations alpha or beta globin genes, is characterized by either no or too little hemoglobin — the protein that transports oxygen in red blood cells. Patients can experience a range of symptoms such as anemia, weakness, fragile bones and diminished fertility.
The main goal of ≥ 1.0 g/dL increase in Hb concentration was met by about 92% of the 13 patients ready for evaluation following 12 weeks of treatment — the mean change from baseline for the evaluable patients was 1.34 g/dL over weeks 4-12. Other markers of red blood cell function and performance also favored the drug.
Acceleron’s Reblozyl, which is engineered to work by targeting a protein necessary to enhance the production and maturation of red blood cells, was approved last year for more severe beta-thalassemia patients who are transfusion-dependent. Meanwhile, bluebird bio, has an eye-poppingly expensive gene therapy to combat the disease approved in Europe, and is aiming for a US nod.
Akin to bluebird, whose gene therapy is also primed for use in sickle cell disease, Jackie Fouse-led Agios is also testing mitapivat in the blood disorder that is characterized by atypical hemoglobin molecules, which can distort red blood cells into a sickle, or crescent, shape.
Early data from an ongoing phase I SCD trial testing multiple mitapivat doses (5 mg, 20 mg, 50 mg) showed the company had enrolled 9 patients till date — each got the drug for two weeks, before being tapered off. One patient discontinued the trial due to a pre-existing condition, but the remaining 8 were evaluated.
Five out of 8 patients achieved the main goal of enhancing hemoglobin levels by ≥1.0 g/dL from baseline. Data showed the use of the drug was associated with decreases in hemolytic markers.
Until recently, the treatment landscape for the disease was barren, but the last few years have seen a trifecta of approvals. Most recently, last November saw two approvals: Novartis’ therapy, Adakveo, designed to prevent periodic episodes of searing pain called vaso-occlusive crises (VOCs) that deprive the body of oxygen-rich blood and Global Blood Therapeutics’ Oxbryta, which works by increasing hemoglobin’s affinity for oxygen. Mitapivat is expected to work in SCD by decreasing a salt in red blood cells that plays a role in liberating oxygen from hemoglobin in peripheral circulation and enhancing levels of a central metabolite called adenosine triphosphate (ATP).
Agios also has two pivotal studies testing mitapivat in pyruvate kinase deficiency, a rare inherited disease that is characterized by the accelerated destruction of red blood cells. Data from these trials are expected later this year or early 2021.
Separately on Friday, Agios said it was relinquishing its royalty rights on global net sales of Bristol Myers Squibb’s Idhifa, as as its rights to receive up to $55 million in outstanding regulatory milestone payments from Bristol Myers Squibb, to Royalty Pharma for $255 million.
The drug, allied with Celgene (now a Bristol Myers company), was approved in 2017 for use in acute myeloid leukemia.