Agios, a leading US-based cancer biopharmaceutical company and a pioneer in cellular metabolic therapies for cancer and rare genetic diseases, recently announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to its targeted anticancer drug Tibsovo (ivosidenib) for the treatment of adult patients with relapsed or refractory myelodysplastic syndromes (MDS) confirmed by an FDA-approved test to harbor a susceptibility IDH1 mutation.
Tibsovo is an oral targeted inhibitor of isocitrate dehydrogenase-1 (IDH1) and was approved by the FDA in July 2018 for adult patients with relapsed or refractory acute myeloid leukemia (R/RAML) confirmed by an IDH1 mutation using an Abbott RealTime IDH1 companion diagnostic kit. This approval makes Tibsovo the first FDA-approved drug for the treatment of IDH1-mutant R/RAML.
BTD (Best Before Treatment) is a new drug review pathway established by the FDA in 2012 to expedite the development and review of new drugs for treating serious or life-threatening diseases with preliminary clinical evidence demonstrating substantial improvement compared to existing treatments. Drugs granted BTD receive closer guidance during development, including from senior FDA officials, ensuring new treatment options are available to patients in the shortest possible time.
The FDA granted BTD for Tibsovo in the treatment of MDS based on data from an ongoing Phase I dose-escalation and expansion study of MDS in hematologic malignancies. The results were presented at the 7th Annual Meeting of the Society of Hematologic Oncology in September 2019. These results demonstrate that Tibsovo monotherapy is well-tolerated in patients with relapsed or refractory MDS due to IDH1 mutations and is associated with durable remission and achieving and maintaining transfusion-free status. Among the 12 patients who received 500 mg of Tibsovo orally daily, the median duration of treatment was 11.4 months, the median age was 72.5 years, and 42% of patients were over 75 years of age.
As of November 2, 2018, 75% (9/12) of patients achieved disease remission, and 42% (5/12) achieved complete remission (CR). The median duration of CR has not yet been reached (95% CI: 2.8 months - NE). Among patients with CR, 60% remained relapse-free for 12 months. Additionally, 9 patients (75%) had transfusion-free days of 56 days or longer during the study period. The most common adverse events (AEs) of any grade were back pain, diarrhea, fatigue, and rash. Grade 2 IDH differentiation syndrome was observed in 1 of the 12 patients. No adverse events led to permanent treatment discontinuation.
