It’s happened– the first high-profile failure from the re-emerging cohort of publicly traded gene therapy developers. Celladon (CLDN) reported on Sunday that MYDICAR, the company’s experimental treatment for heart failure, failed to outperform a placebo in the phase II CUPID2 trial.
In the two days since, the biotech sector has been routed. This may be partially attributed to Celladon’s failure, but major media publications have been re-hashing the “sustainability of drug prices” story as well (see here and here).
MYDICAR employs [employed?] an adeno-associated virus (AAV) to deliver a functional SERCA2a gene to heart muscle cells. Celladon’s expectation was that increased SERCA2a would improve heart function in these heart failure patients.
Not the case. MYDICAR compared to placebo resulted in a hazard ratio of 0.93 (0.53, 1.65 95%CI) (p=0.81) for the primary endpoint in CUPID2 – heart failure-related hospitalizations or ambulatory treatment for worsening heart failure. Secondary endpoints including all-cause death, need for a mechanical circulatory support device, or heart transplant, also failed to show a significant treatment effect for MYDICAR.
The efficacy analysis was performed on a modified intent to treat population (mITT, n=243). This suggests that MYDICAR likely performed even worse on an ITT basis. Celladon noted that outcomes on all other endpoints (improvement in New York Heart Association classification, 6 Minute Walk Test, and Quality of Life) were consistent with no treatment effect.
CUPID2 failed unequivocally. What we don’t know is exactly why, though we have our suspicions. Was it the target protein (SERCA2a)? A failure of the vector (AAV1) to deliver? Not enough viable capsid? It’s not clear that the medical community will ever have a good answer to this.
More important for investors, is there a logical read-through to the rest of the gene therapy developers? This includes, most prominently, Spark Therapeutics (ONCE), bluebird bio (BLUE), Avalanche Biotechnologies (AAVL), AGTC (AGTC) and uniQure (QURE).
Our view – no. Here’s why. 
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