December 07, 2016
Researchers at the Children's Hospital of Philadelphia have made headway on a gene therapy approach to treating patients with hemophilia B, finding that an experimental product achieved the highest levels of sustained success in clinical trial participants with the inherited bleeding disorder.
The investigation, led by CHOP hematologist Lindsay A. George, set a goal of reaching an essenial blood-clotting factor IX by way of gene therapy, the emerging treatment method that delivers nucleic acid polymers directly into a patient's cells.
Mutations in the gene for factor IX, one of the foundations of blood coagulation, can lead to deficiencies that result in hemophilia B.
Early results from the clinical trial, sponsored by Pfizer and Spark Therapeutics, were released Monday by the American Society of Hematology. Nine adult hemophilia B patients, aged 18 to 52 years, received a single dose of a gene therapy product engineered to enter their liver cells and stimulate production of factor IX.
“Our goal in this trial was to evaluate the safety of the gene therapy product and secondarily, to determine if we could achieve levels of factor IX that could decrease bleeding events in patients," said George. "These patients have a severe or moderate level of hemophilia, with baseline clotting factor level less than or equal to 2 percent of levels in healthy people. In current treatment, patients with hemophilia give themselves intravenous doses of factor IX up to a couple times a week. While generally effective, factor levels fluctuate, and patients may suffer painful, disabling joint bleeds when their clotting factor levels drop. Such a regimen requires significant planning of daily activities."
Patients participating in the current trial successfully maintained factor levels of about 30 percent, a near-normal measure that generally enables patients to forego self-treatment to avoid bleeding events. Only in the event of surgery or major trauma would such patients be expected to experience bleeding.
“This represents a potential dramatic improvement in their quality of life and a shift in the way we think about treating hemophilia," George said.
With the exception of one patient who self-infused factor IX two days after treatment, none of the trial participants needed supplemental help. Six of the first seven patients reported an increase in physical activity and all patients noted an improvement in their quality of life. Two other patients received the gene therapy vector too recently to determine such measures.
The success of the phase 1/2 clinical trial marks an advancement over previous gene therapy trials to intervene in hemophilia patients, many of whom have experienced adverse immune responses in the past. Pending the longer-term results of the trial, George the next step will be to consult with the U.S. Food & Drug Administration to develop a larger phase 3 clinical trial. To date, no gene therapy products for genetic diseases have gained FDA approval in the United States.