A drug used to treat a form of adult leukemia has shown efficacy in a form of bile duct cancer that has no approved treatments.
On Monday, Cambridge, Massachusetts-based Agios Pharmaceuticals announced the presentation of data from its 185-patient Phase III ClarIDHy trial of Tibsovo (ivosidenib) in IDH1 mutation-positive advanced cholangiocarcinoma. The drug, an IDH1 inhibitor, is currently approved to treat relapsed or refractory acute myeloid leukemia with an IDH1 mutation. The data were presented at the European Society for Medical Oncology (ESMO) meeting in Barcelona, Spain.
The company said it plans to submit a supplemental approval application for the drug by the end of the year.
According to the data, patients in ClarIDHy who received Tibsovo experienced a 2.7-month improvement in progression-free survival, or PFS, meaning the amount of time that patients live without their disease worsening. Patients receiving placebo saw a 1.4-month improvement. The results, measured by independent radiological review, were deemed statistically significant. The estimated rates of PFS at six months and 12 months were 32 percent and 22 percent, respectively, while none of the patients who received placebo were free from progression at that time.
“Advanced cholangiocarcinoma is an aggressive disease oftentimes characterized by rapid progression following multiple lines of therapy, and there are no currently approved treatments,” said Memorial Sloan Kettering oncologist and presenter of the data at ESMO Dr. Ghassan Abou-Alfa, in a statement. “The ClarIDHy study is the first randomized trial in previously treated IDH1-mutant cholangiocarcinoma patients and demonstrates that Tibsovo provides significant improvement in PFS compared to placebo, while showing a favorable trend in overall survival.”
PFS is the primary endpoint of the study, while overall survival is one of the secondary endpoints, according to the study page on ClinicalTrials.gov. The overall survival trend fell slightly outside the threshold for statistical significance, with a p value of 0.06, according to a slideshow presentation during a conference call with investors. Patients in the placebo arm who progressed were allowed to cross over and receive the drug.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Cholangiocarcinoma is rare, being diagnosed in about 8,000 people in the U.S. each year, according to the American Cancer Society, with IDH1-mutant disease being a rarer subset. Incyte also has a drug in registration-directed development for cholangiocarcinoma, pemigatinib, though it is an FGFR inhibitor and thus would not compete directly with Tibsovo.
In addition to cholangiocarcinoma, Agios is also testing Tibsovo in early-stage studies of other solid tumors, including a perioperative study in glioma, a form of brain cancer, and a Phase I dose-escalation and expansion study in solid tumors, according to its pipeline page. The company’s other approved drug is Idhifa (enasidenib), an IDH2 inhibitor, which is approved for IDH2 mutation-positive AML. Celgene has worldwide development and commercialization rights to Idhifa, while Agios has co-promotion and royalty rights in the U.S.
Other drugs in Agios’ clinical pipeline include the pan-IDH inhibitor vorasidenib, for glioma and other solid tumors; the PKR activator mitapivat, for thalassemia and PK deficiency; the MAT2A inhibitor AG-270, for MTAP-deleted tumors; and the DHODH inhibitor AG-636, for lymphoma.
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