Welcome to your weekly digest of approaching regulatory and clinical readouts. Celyad (OTC:CLYYF) is awaiting the first phase III results in the next few months with its lead candidate, C-Cure, which, being the most advanced cell therapy in cardiovascular disease, should lay down a marker for others in the field.
Meanwhile, the second half will see data emerge from the phase IIb Aegis-1 trial of CSL Behring's infused HDL, CSL112, in patients with acute coronary syndrome. The study design is robust, having enrolled 1,258 patients and using an outcomes-based efficacy endpoint, but safety will be closely watched; CSL previously shelved a similar formulation after it caused liver enzymes to spike.
Heart of the matter
Celyad expects to report results from the Chart-1 study by the end of June. If positive, they will allow the company to submit C-Cure for approval in Europe in November. The company notified the EMA of its plans last week, triggering the appointment of rapporteurs.
Chart-1 will compare the C-Cure injection with a sham treatment in 240 ischaemic heart failure patients. Its primary outcome is the difference between the two groups at 39 weeks on a hierarchical composite endpoint, including time to death, number of worsening heart failure events and change in left ventricular ejection fraction.
The company is also moving towards US approval, with patients now being recruited into the Chart-2 trial, which has a simpler primary endpoint of six-minute walk test at 39 weeks post procedure, and a primary completion date of June 2016.
Perhaps illustrating caution in the sector, there is currently no sell-side consensus forecast for C-Cure in EvaluatePharma, unusual for a phase III project. Edison analysts estimate the probability of success for Chart-1 at 45%.
But Celyad has bigger fish to fry, hoping to partner C-Cure in 2017, which would allow the company to focus on its adoptive T-cell therapy projects. A phase I trial of autologous T cells engineered to express a natural killer cell receptor is under way in acute myeloid leukaemia and multiple myeloma.
Of course, hooking a partner for C-Cure depends on positive Chart-1 results, but Celyad will not be the only company eagerly awaiting its outcome; positive data could be an endorsement for the field in general, boosting the likes of Vericel (NASDAQ:VCEL).
Negative data would be yet another setback, not just for Celyad, but also for those following in its wake.
Reconstituted HDL infusion therapies like CSL's CSL112 cause a rapid elevation in apoAI and in pre-βHDL particles. Levels of apoAI have been shown to double, and the rise in pre-βHDL can be more than 30-fold.
This means HDL infusions might prevent acute vascular events in the immediate time frame. They are intended as a different kind of therapy to oral anti-cholesterol agents, such as PCSK9s, which elevate HDL over weeks to months, and are therefore intended for long-term use.
Aegis-1 is comparing two doses of CSL112, 6g or 2g, administered in four weekly infusions, against placebo. The secondary endpoint, designed to assess the drug's efficacy, is the time to first occurrence of a major adverse cardiovascular event (MACE). The patients are considered high-risk, having had a heart attack during the previous week.
The primary endpoints, though, concern liver toxicity, with levels of alanine aminotransferase, bilirubin and serum creatinine being tracked during the first 29 days of the study. CSL abandoned CSL111, an earlier HDL mimetic, after it showed transient elevations of liver enzymes.
In an investor presentation in December, the group said Aegis-1's data monitoring committee had confirmed safety to-date. Promisingly, CSL112 did not show liver enzyme elevation in phase II.
CSL is confident enough of its success to have begun plans for a phase III trial. This study, due to start in just over a year, will also include high-risk patients and have MACE as its primary endpoint.
Though CSL112 is in the same therapy category, it will not make the kind of sales seen by chronic therapies such as Repatha and Praluent, let alone Lipitor. But it is designed for a different setting, and here it could be successful if it can show itself to be safe.