[Corrected 4/10/14, 12:25 pm. See below.] The FDA has granted its “breakthrough therapy” designation for a gene therapy treatment in mid-stage development by San Diego’s Celladon (NASDAQ: CLDN), for patients with advanced heart failure.
The FDA notified the company in a letter sent by fax Wednesday from the Office of Cellular, Tissue and Gene Therapies, according to Fredrik Wiklund, Celladon’s vice president for corporate development and investor relations. It is the first time the FDA has given the designation to a gene therapy program, and means the development and review of Celladon’s Mydicar therapy can be expedited, Wiklund said.
Celladon sought the designation based on a long-term, follow-up study of Cupid 1, a mid-stage clinical trial that enrolled 39 patients with severe heart failure. Patients either got a placebo or a low, mid, or high dose of Mydicar through cardiac catheterization. Results from the follow-up study, released in November, confirmed initial findings that showed a dramatic, 88 percent reduction in heart failure-related hospitalizations among patients who received the highest dose of the gene therapy treatment.
After three years, the patients who got the highest dose of Mydicar still showed an 82 percent reduction in episodes of worsening heart failure and hospitalizations.
“That’s what really crystallized the strength of the data,” Celladon CEO Krisztina Zsebo said Wednesday. The safety data for Mydicar also was “superb,” and shows no drug-related toxicities, Zsebo added.
The high-dose Mydicar patients also showed an improved survival rate throughout the three-year follow-up study. Heart failure represents a large, unmet need, and the mortality rate is roughly 50 percent within five years of the initial diagnosis of heart failure, according to the company.
A second clinical trial that is intended to confirm and expand on the results of Cupid 1 began in February, after enrolling 250 patients. “For Europe, this is a pivotal study,” Zsebo said. “For the U.S., it’s still to be determined whether we need to do a phase 3 trial or not.”
Celladon’s gene therapy is intended to boost production of an enzyme known as SERCA2a that plays a key role in recycling calcium in the heart’s muscle cells. Heart muscle cells need calcium to contract and relax, and a variety of conditions—such as coronary artery disease, diabetes, and alcoholism and drug abuse—can contribute to progressive heart failure. Regardless of the cause, heart failure typically leads to a loss of enzyme function. As a result, the heart cannot pump blood forcefully enough to keep fluid out of the tissues and lungs. Patients’ legs and arms swell, they feel a constant shortness of breath, and occasionally experience acute episodes that feel like drowning—requiring emergency room treatment or hospitalization.
Celladon is developing a treatment that uses a small, benign virus to deliver a fresh supply of SERCA2a enzymes into the muscle cells of the heart. The company says Mydicar is intended for patients who have been diagnosed with advanced chronic heart failure and who are suitable for this particular type of gene therapy. The company estimates that about 350,000 patients with systolic heart failure fit this criteria in the United States.
Current treatment options for such patients are usually expensive and involve a heart transplant or the surgical implantation of a pump known as a left ventricle assist device.
In general, over 6 million people are currently diagnosed with heart failure in the United States. There are more than 1 million heart failure-related hospitalizations and about 280,000 deaths each year.
A treatment that reduces heart failure-related hospitalizations by more than 80 percent could have a dramatic impact on healthcare costs. By one recent estimate, the direct costs of heart failure in the United States is $60 billion a year—with heart failure-related hospitalizations pegged at $37 billion.
“That’s why reducing hospitalizations by 88 percent is such a big deal,” Zsebo said.
The FDA’s breakthrough therapy designation was enacted as part of the FDA Safety and Innovation Act in mid-2012. It means the FDA has determined that an experimental therapy addresses a serious or life-threatening condition, and preliminary clinical data indicates the drug may “demonstrate substantial improvement over existing therapies.”
While FDA regulators have granted the designation to 40 small-molecule compounds over the past two and a half years, only two biologics were designated as breakthrough therapies as of March 31, according to the FDA. Mydicar would be the third, and the first gene therapy to win the designation.
[Updated to show AGTC completed IPO, instead of pending] Although initial forays into gene therapy were stymied in the 1990s, the field has rebounded in recent years. Forbes recently reported that 11 different companies have raised at least $668 million from venture capitalists and the public markets since the beginning of 2013, and one more, Florida-based AGTC, completed a $50 million initial public offering earlier this month.
Once the FDA has designated a drug development program as a breakthrough therapy, the agency says, it will work closely with the company developing the drug to ensure that the clinical trials can be conducted as efficiently as practicable.