Futility analysis augurs defeat in pivotal trial testing of NuCana's lead drug in metastatic pancreatic cancer
Nearly two years after making its public debut, UK-based NuCana’s mission to make chemotherapies more potent and safer was dealt a blow, after a pivotal study testing its lead experimental drug halted enrollment in a hard-to-treat advanced form of cancer, following a futility analysis.
The drug, Acelarin, is being evaluated for use in metastatic pancreatic cancer patients who were not considered suitable for combination chemotherapy. In the late-stage ACELARATE study — which compared the experimental drug against the chemotherapy gemcitabine — 200 patients had been enrolled by the sponsor, Clatterbridge Cancer Centre, before an analysis from an independent safety and data monitoring panel suggested the study’s main goal would not be met.
NuCana’s Pro-Tides technology — which emerged out of a Cardiff University laboratory led by the company’s late chief scientific officer, Christopher McGuigan, is designed to supercharge chemotherapy —specifically nucleoside analogs (molecules that mimic the structure of components of nucleic acids, but are designed to interrupt the replication of genetic material and thereby cause cancer cell death). The technology is engineered to improve the efficacy of these chemotherapeutic agents by curtailing the resistance put up by cancer cells and optimizing their side-effect profile by diminishing the toxicity they typically brandish.
In the case of Acelarin — a purported gemcitabine upgrade — the ProTide’s chemical structure is designed to enable its entry into the cancer cell independent of membrane transporters and protecting it from both extracellular and intracellular degradation, thereby enhancing its potency.
The primary endpoint of the trial was to achieve at least a 42% reduction in risk of death compared to gemcitabine. After reviewing the analysis, the sponsor decided to suspend study recruitment — but allow the 25 patients who are seeing some benefit to continue with the drug.
“There were imbalances in unfavorable prognostic factors for the patients in the Acelarin arm which may have impacted the futility analysis. In particular, 54% of the patients in the Acelarin arm were diagnosed at the most advanced stage T4, compared to 36% of patients in the gemcitabine arm,” Daniel Palmer, the trial’s chief investigator, said on Tuesday. “We need to allow the data to mature and conduct additional analyses, including biomarker assessment, in order to determine the most appropriate course of action.”
Correcting for such variable factors, the company has asserted it is seeing positive survival trends for Aclerarin (versus gemcitabine) in the difficult-to-treat population, although the data is not yet mature enough to be quantified. These numbers can be expected in the first quarter of next year, Jefferies analyst Eun Yang wrote in a note.
The drug is also being tested in both platinum-resistant and platinum-sensitive ovarian cancer as well as a first-line treatment in biliary cancer, for which there are no approved treatments.
Though pancreatic cancer “accounted for a third of our valuation given its most advanced stage, key value drivers are chemo combo with Acelarin in biliary cancer (Ph3) & NUC-3373 in colorectal cancer (Ph1 efficacy data in 2020),” Yang wrote in a note entitled “Clinical Setback for Acelarin, but Combo Therapy & Pipeline Potential Remain.”
Shares of NuCana $NCNA tumbled more than 20% on Tuesday after the announcement but pared some of those losses in Wednesday premarket trading. The stock was up about 3% at 7.55 before the bell. In September 2017, the company went public at $15/share. The much-maligned Woodford Investment Management, which suspended fund redemptions earlier this year, is one of NuCana‘s largest shareholders owning a 10% stake.
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