Celladon Corporation (NASDAQ: CLDN) expects to announce topline results from the Phase IIb trial (CUPID 2) of gene therapy MYDICAR in patients with systolic heart failure in April 2015. Many investors asked me to write about the trial. Here is my due diligence.
Celladon’s lead product candidate, MYDICAR, uses gene therapy to target SERCA2a. SERCA2a is a Ca2+-ATPase that becomes deficient in patients with heart failure. Although SERCA2a was validated as a target for heart failure in the 1990s, no company has been successful in targeting SERCA2a using traditional methods.
MYDICAR utilizes AAV1 (adeno-associated viral 1) vectors to deliver SERCA2a gene. Celladon expects a single intracoronary infusion of MYDICAR to reduce heart failure-related hospitalizations.
In the 39-patient Phase IIa trial, the hazard ratio at 12 months for high-dose MYDICAR (1×10^13 DRP) vs. placebo was 0.12 representing a risk reduction of 88%. Benefit has been confirmed at three years with a risk reduction of 82%. In April 2014, the FDA granted Breakthrough Therapy designation to MYDICAR. This is the first gene therapy product granted this designation.
Celladon completed enrollment of the 250-patient Phase IIb trial in February 2014. In the Phase IIb trial, patients received high-dose MYDICAR. The new trial (NCT01643330) expanded enrollment to older patients (76-80) and patients with mild symptoms (NYHA Class II).
|Trials||CUPID 1 (Phase I/IIa)||CUPID 2 (Phase IIb)|
|Doses||1.4×10^11 to 1×10^13 DRP||1×10^13 DRP|
|NYHA Classes||Class III/IV||Class II/III/IV|
These changes may complicate the Phase IIb results, but Celladon still have great chance to success. The company expects to detect an at least 45% risk reduction (hazard ratio of 0.55). This is a really easy goal for MYDICAR. In the Phase IIa trial, even low-dose MYDICAR achieved a risk reduction of 60%.
Moreover, Celladon has obtained an SPA from the FDA that the primary efficacy endpoint of time to recurrent events would be acceptable for a pivotal trial of MYDICAR. According to Celladon’s SEC filings, the FDA may not require additional efficacy trials if the results from the Phase IIb trail satisfy FDA’s requirement.
There are over 280,000 heart failure-related deaths annually in the U.S. Approximately 40% of patients are AAV1 neutralizing antibody negative and therefore eligible for MYDICAR. Needless to say, MYDICAR has blockbuster potential.
In October 2014, Celladon entered into a agreement with Lonza to build a new facility for the manufacture of MYDICAR. The detailed design for the facility is expected to be completed by April 2015. In September 2014, Celladon appointed Scott Garrett, the former Senior Marketing Director of Gilead Sciences, as Vice President, Commercial Planning. These actions suggest Celladon executives are feeling fairly confident.
I don’t worry about insiders selling. Several executives at Pharmacyclics (NASDAQ: PCYC) sold their shares at $120-140 in 2014H2, now $257 per share. Celladon’s fate entirely hangs on the success of MYDICAR. Just wait for the Phase IIb data.