Krisztina M. Zsebo, CEO of San Diego’s Celladon, went to the annual meeting of the American Society of Gene Therapy to bust some scientific myths about the experimental technology.
The conference is meeting this week in San Diego, and when I caught up with her before her talk yesterday, she wasted no time busting myths about the corporate side of gene therapy as well.
Zsebo rejected the notion that venture financing for gene therapy companies has completely dried up. She pointed out that Celladon, which is working on a gene therapy for heart failure patients, received $9 million in venture funding earlier this year and stands to get $5.6 million more if certain milestones are met. What’s more, Celladon is in discussions with several pharmaceutical companies and expects to announce a development partner in the near future, she said.
Celladon is not an anomaly, she noted. This month, Applied Genetic Technologies, a Florida company working on a gene therapy for age-related macular degeneration with Cambridge-based Genzyme, received $11.8 million in venture funding.
There’s no question the economic environment is difficult, she acknowledged. But, “if you have a solid program, a strong mechanism of action and strong data … there are potential investors out there.”
Not that Celladon is immune to the misfortunes of other gene therapy firms. Seattle’s Targeted Genetics, which faces possible bankruptcy, manufactured Celladon’s drug. But Zsebo said Celladon has stockpiled enough of the drug to complete its clinical trials, and is working with Sigma-Aldrich, a contract manufacturer based in St. Louis, to produce the commercial product.
Gene therapy involves using a healthy gene to replace a defective or missing gene to relieve symptoms and cure chronic disease. A benign virus is used as vector to carry the healthy gene into a patient’s cells.
Celladon’s gene therapy uses a virus to deliver a gene that encodes for the SERCA2a enzyme, a key factor in maintaining a healthy heartbeat that is deficient in heart failure patients. The gene therapy is administered directly to the heart through a catheter that is thread through a large artery in the thigh. The theory is that heart cells will take up the gene, which revamps the cell machinery to produce increased amounts of the enzyme, improving the heart’s ability to contract.
Last month, Celladon published results of an early-stage trial of nine patients in the Journal of Cardiac Failure. The study reported no significant safety issues and found that six months after treatment five patients had improved symptoms and increased left ventricular function. The left ventricle is the chamber of the heart that pumps blood to the body and is typically impaired in heart failure patients. Two patients with low levels of pre-existing antibodies showed no improvement.
Celladon has enrolled 20 of an anticipated total of 37 patients in a mid-stage trial; results are expected by early 2010. The trial is for people with advanced heart failure – those who become winded performing routine activities, like getting up to answer the phone. Zsebo said such patients are “on the trajectory” for a heart transplant or for receiving a left ventricular assist device, an implantable mechanical heart pump. About 1.5 million Americans have advanced heart failure.
The potential market for the drug could be half that number, however. UC San Diego cardiologist and Celladon adviser Howard Dittrich said half of the patients recruited for the mid-stage trial were rejected because they had low levels of antibodies to the virus, and scientists have concluded the gene therapy won’t work for them. This could mean that 50 percent of people with advanced heart failure won’t be eligible for Celladon’s drug.
Celladon, with five employees and 10 contract workers, has enough money to complete the mid-stage study and fund the company through completion of a partnering transaction, Zsebo said. Celladon was spun out of the UC San Diego incubator in 1994.
At the meeting this week, Zsebo shared some of the scientific lessons the company has learned working on its gene therapy, called Mydicar.
One myth Zsebo hoped to put to rest was the notion that gene therapy can’t be safely administered through the bloodstream. The worry was that the gene would end up organs where it didn’t belong and cause havoc. But Celladon found that wasn’t the case. The immune system ultimately eliminated the virus from the body, Zsebo said, and the SERCA2a gene was not expressed in cells outside the heart.