- Updated results from two Phase 3 studies of Celgene and Acceleron Pharma's experimental drug luspatercept helped to support the big biotech's bet on the therapy, which is being developed for several blood disorders.
- The data, which was highlighted over the weekend at the annual meeting of the American Society of Hematology in San Diego, showed luspatercept significantly reduced blood transfusion burden in patients with beta-thalassemia and myelodysplastic syndromes (MDS).
- Celgene and Acceleron aim to submit the drug for approval in both indications in the first half of next year. Celgene has touted the drug to investors as capable of reaching $2 billion in peak annual sales.
The ASH annual meeting, always important for Celgene, has become a key test of the biotech's effort to regain investor trust this year.
Feeling the ill effects of financial forecast revisions and clinical missteps, the company spent 2018 talking up a freshly reloaded pipeline — part of which will be on display at the hematology conference.
Luspatercept, which will be featured in the plenary session Sunday, headlines the more than 100 abstracts that Celgene will present over the four-day conference.
An erythroid maturation agent, luspatercept works to enhance the production of red blood cells. In the BELIEVE study, Celgene and Acceleron tested the drug in adults with anemia related to beta-thalassemia and required regular transfusions.
On the trial's primary measure, the companies' therapy led to a reduction in transfusion burden of more than one third in roughly a fifth of patients, compared to only 4.5% of those on placebo, in weeks 13 through 24. Measuring over any 12-week period during the study, luspatercept reduced transfusions by a third in 70% of patients versus only 30% of those on placebo.
Beta-thalassemia patients require regular, lifelong blood transfusions that cause other side effects, such as iron build-up. Cutting that could help mitigate those co-morbidities and improve quality of life.
On safety, serious adverse events were reported in 15% of patients receiving luspatercept, compared to 5.5% on placebo. No luspatercept-treated patients died due to treatment-emergent adverse events.
Luspatercept's potential role could be threatened by advances from gene therapies for the condition. Maria Cappellini of the University of Milan and an investigator in the BELIEVE study isn't sure that will be the case, however.
“Gene therapy must be — to be really efficacious — a cure," she said in a Saturday press conference. "You’re not going to perform gene therapy for reducing transfusion burden. That’s not the scope."
In MEDALIST, which will be presented Sunday, nearly 40% of patients with a certain subtype of low- or intermediate-risk MDS were able go at least eight weeks without a blood transfusion, compared to just 13% of those on placebo.
That comparison might actually look less favorable than it really is, noted Alan List, CEO of the Moffit Cancer Center and an investigator in the MEDALIST study.
"Patients on the placebo arm who responded had a very low transfusion burden at baseline and they exceeded that eight-week threshold of response simply by virtue of changes in transfusion period compared to baseline," he said in a press conference on Saturday.
For MEDALIST, Celgene and Acceleron only looked at MDS patients with ring sideroblasts who have failed or are ineligible to receive erythropoietin-stimulating agents (ESA) like Amgen's Epogen (epoetin alfa).
What's not clear, given the study's aim, is how well this drug would work in patients without ring sideroblasts, which are a morphological subtype of MDS associated with a gene mutation.
If the companies' application wins over the Food and Drug Administration next year, luspatercept could become the first new drug approved for MDS in 12 years.
During the third quarter, Celgene and Acceleron also began a Phase 3 study testing luspatercept against epoetin alfa in front-line MDS patients at low or intermediate risk who had not previously received an ESA.
"My expectation is it will be very favorably compared to an ESA and probably more effective because it will work in patients who are transfusion dependent," List said.