Agios Pharmaceuticals said it agreed with Celgene to end a three-year-old collaboration to develop and commercialize treatments containing its most advanced clinical cancer candidate AG-881 (vorasidenib), an oral inhibitor of both the isocitrate dehydrogenase-1 (IDH1) and IDH2 proteins.
Agios stated in a regulatory filing that it will obtain sole global rights to AG-881. In return, Agios agreed to pay Celgene low-single-digit royalties on worldwide net sales of products containing AG-881—as well as split with Celgene worldwide development costs for AG-881 through December 31, 2018.
According to the filing, Celgene and its affiliates are prohibited from developing, manufacturing, or commercializing any product that IDH1 at specified levels of binding for any indication—while Agios is barred from developing, manufacturing, or commercializing AG-881 in hematologic indications.
The filing offered no reason for the termination. According to Agios’ Form 10-Q quarterly filing for the second quarter, Celgene may terminate the collaboration “for any reason upon ninety days written notice to us,” while either company can terminate all or part of collaboration due to “an uncured material breach by the other party that frustrates the fundamental purpose of the AG-881 Agreements,” or due to the insolvency of any of the companies.
The termination comes three months after Agios presented its first data from an ongoing Phase I study (NCT02481154) assessing AG-881 as a single agent in advanced glioma and other solid tumors at the American Society of Clinical Oncology (ASCO) Annual Meeting.
The data showed that as of the March 29, 2018 data cut-off, among the 52 patients with glioma, 75% (39) had a best response of stable disease, including 20 patients with non-enhancing disease. Among the 41 patients with non-glioma solid tumors, one patient with cholangiocarcinoma had a partial response, 37% of patients (15) had stable disease, and 44% (18) had progressive disease. AG-881 showed a favorable safety profile at dose levels below 100 mg, Agios said at the time.
‘Encouraging’ Data
“The AG-881 Phase I dose-escalation data are encouraging, as they demonstrate a favorable safety profile at lower dose levels and show signals of clinical activity that support further evaluation of the role of inhibiting mutant IDH in low-grade glioma,” Ingo Mellinghoff, M.D., a medical oncologist at Memorial Sloan Kettering Cancer Center and an investigator for the study, stated in a June 1 press release issued by Agios.
AG-881 is also under study in another Phase I trial that was still recruiting patients as of July 23 (NCT03343197). That trial is designed to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-881 or Tibsovo® (ivosidenib; formerly AG-120).
Tibsovo is Agios’ IDH1 inhibitor that was approved July 20 by the FDA for patients with relapsed or refractory AML (R/R AML) with a susceptible IDH1 mutation as detected by an FDA-approved test. Tibsovo is the first and only FDA-approved treatment for the indication, according to Agios.
Agios and Celgene agreed to develop products based on AG-881 in April 2015. Celgene paid Agios $10 million upfront and was eligible for up to $70 million in potential payments tied to achieving milestones—$15 million for the filing of a first NDA in a “major” market, and up to $55 million for achieving regulatory milestones.
The agreement allowed Agios to receive royalties at tiered, low-double digit to mid-teen percentage rates on net sales if it opted not to participate in the development and commercialization of AG-881.
The companies also agreed to split all worldwide development costs equally, with specified exceptions, as well as any profits from any net sales of, or commercialization losses related to licensed AG-881 products.
Agios and Celgene initiated their first global collaboration in 2010, focused on cancer metabolism. The companies last year launched an additional anticancer drug development program focused on methylthioadenosine phosphorylase (MTAP)-deleted cancers as part of their potentially $1 billion metabolic immuno-oncology collaboration, signed in May 2016.
