The first interim results from Celgene’s open-label, randomised Phase II (NCT02677922) study were announced at the 2019 annual American Society of Hematology (ASH) conference on 7–10 December in Orlando, Florida, US.
The findings showed that the addition of the isocitrate dehydrogenase 2 (IDH2) inhibitor Celgene/Agios Pharmaceutical’s Idhifa (enasidenib) to low-intensity chemotherapy can benefit patients with acute myeloid leukaemia (AML) harbouring mutations in the IDH2 gene.
Idhifa is FDA-approved for the treatment of patients with IDH2 mutations in the relapsed/refractory setting (R/R). This trial was the first to demonstrate a benefit in the front-line setting for patients who are ineligible for intensive chemotherapy.
The addition of Idhifa to the hypomethylating agent azacitidine led to complete remission (CR) or complete remission with incomplete recovery (CRi) in 59% of patients compared to 24% of patients in the azacitidine monotherapy arm.
The adverse effects were similar in both arms, and the safety profile of the combinatorial regimen was consistent with the safety profile of each agent alone. While premature, these data suggest that Idhifa is another option in the low-intensity induction setting, offering more options for IDH2-mutant patients.
As Idhifa is already approved for R/R patients, combined with its current off-label use in the front-line setting, this could expedite a label expansion for use in the newly-diagnosed setting. This would mean that Idhifa could be available for an additional 2,000 newly-diagnosed AML patients in the US every year.
However, while these data may offer enough backing for Agios to submit a New Drug Application, the recent approval of AbbVie/Genentech’s Venclexta (venetoclax tablets) in the same setting will provide competition. In 2018, Venclexta gained accelerated FDA approval based on an aggregate 67% CR+CRi response rate in combination with azacitidine or decitabine in the same patient population.
Venetoclax is well tolerated and has been widely adopted by physicians, suggesting that Idhifa, if approved, will share a piece of this market with Venetoclax. As such, it remains to be seen whether oncologists will opt to use the targeted therapy approach of Idhifa upfront or follow the established path of using Venclexta first and then switch to Idhifa on relapse. Results from the upcoming Phase III trials will shed more light on the optimal treatment sequence.
While the front-line setting of young/fit AML patients is dominated by chemotherapy regimens, the unfit and R/R patient market has seen a significant rise in branded therapies since 2017. Due to label expansion efforts and new agents entering the market, GlobalData estimates that the value of this market will increase significantly over the next five years.