Cyclacel Pharmaceuticals has been taught the meaning of futility. Two years after an independent data monitoring board told Cyclacel its phase 3 acute myeloid leukemia (AML) trial was destined to fail, the ever-optimistic biotech has reported its drug sapacitabine was unable to better the active control in terms of overall survival.
The top-line data confirm an outcome that looked likely from the minute independent advisers told Cyclacel the study had failed an interim futility review in December 2014. By then, the phase 3 trial had chalked up 247 of the 424 patient deaths needed to trigger the end of the study. But, with the review finding no safety issues that would force Cyclacel to shutter the study, the NJ-based biotech pushed ahead regardless.
A little more than two years later, Cyclacel has learnt sapacitabine is no better at improving overall survival in elderly patients with AML than decitabine, an Otsuka drug FDA rejected in the indication in 2012 on the basis that it also failed to outperform the control arm in its own study. Decitabine, sold under the name Dacogen as a treatment for myelodysplastic syndromes, is used off-label in elderly AML patients because of the dearth of options in this population.
When combined with the performance of sapacitabine against some secondary endpoints, the lack of options for elderly patients with AML who cannot or will not undergo chemotherapy has given Cyclacel encouragement to continue seeking a way forward for the drug.
“We plan to discuss the data with European and U.S. regulatory authorities once subgroup analyses are completed over the next few months and will report our further plans as they develop,” CEO Spiro Rombotis said in a statement.
Rombotis and the chair of the phase 3, MD Anderson’s Hagop Kantarjian M.D., picked out the data on complete remission and safety as cause for optimism. Kantarjian, a critic of FDA’s decision to reject decitabine in AML, called the improved rate of complete remission “remarkable.” Cyclacel said the safety of the two arms was similar.
While Rombotis and Kantarjian see the data as suggesting it is still too early to write off sapacitabine, investors were less optimistic. Cyclacel dropped 30% in premarket trading, adding further woes to a stock that is down 99% on the highs it hit a decade ago. The company’s market cap prior to news of the latest setback stood at $24 million.