A plucky US microcap, Celator Pharmaceuticals, looks on track to break a standard-of-care record in oncology that has stood, astonishingly, for nearly 40 years, with early data suggesting it has beaten chemotherapy as a treatment for acute myeloid leukaemia in a randomised phase III trial.
And, if that were not enough, it has reached this point largely without being noticed by investors – something that could represent an achievement in itself given the febrile state of the financial markets. The early results look to have put the group on course to report positive overall survival data next year.
The results came from an ongoing 309-patient phase III study of its lead candidate, CPX-351, versus the standard “7+3” regimen of cytarabine and daunorubicin in the treatment of high-risk secondary AML. This showed a 14-point improvement in induction response rate, a secondary endpoint, with 47.7% of patients on CPX-351 achieving a complete response with or without platelet recovery, versus 33.3% for those on 7+3.
Primary endpoint data – overall survival – and the all-important p values become available in the first quarter of next year, and the omens are good. Induction response rate is considered to correlate closely with OS data, as patients who achieve a complete response and go on to receive a stem cell transplant have much better prognosis than those who receive a transplant when they are not in remission or do not receive a transplant.
The trial is 90% powered to show a 36% reduction in risk of death.
Same components, new formulation
CPX-351 is a combination of the same cytarabine and daunorubicin components used in 7+3, but in a nano-liposomal formulation. At the dosage used this delivers a lower notional dose per cycle of cytarabine and daunorubicin – which could be advantageous in terms of safety – but the pharmacokinetics mean that there is greater cumulative exposure of two components, which presumably contributes to the improvement in efficacy.
Both agents in 7+3 are highly cytotoxic, and the regimen comes with serious side effects including severe anaemia and risk of serious bacterial and fungal infections, all of which contribute to treatment-related deaths. The treatment has to be administered in hospital, so that patients can receive supportive care.
The older therapy is only used in younger, “fitter” AML patients, typically those under 60 years of age. However, the Celator study recruited 60-76 year olds.
An earlier phase II trial showed a non-significant trend to improvement in 60-day treatment-related mortality. If the phase III shows a tolerability, as well as an efficacy, advantage, CPX-351 will certainly become the new standard of care, which would be remarkable given that AML has become famous for being intractable to pharmaceutical development, after perhaps 15 late-stage programmes foundered in this indication.
The long list of failures was joined last year by Cyclacel’s sapacitabine – although patients continue to be monitored in the study, despite having failed an interim analysis for futility. Genzyme was one of a few that managed to show some improvement in efficacy with clofarabine, but with higher induction mortality that caused the eventual abandonment of attempts to gain an approval in AML.
Whether by accident or design, Celator has managed to stay under the radar of most analysts and investors, and despite a 24% rise in its share price yesterday it still has a market cap of under $80m. Indeed, the company’s share price has fallen in the three years since its IPO, despite the current bull market.
Given a likely positive phase III study this valuation seems low by any standards. Celator will be hoping that, once the survival data are reported, investors will finally take notice.