Gene Therapy for hemophilia is all the rage this week. Two days after UniQure announced
preliminary results from their gene therapy to treat hemophilia B patients, Spark Therapeutics released data
from their ongoing phase 1/2 trial of a gene therapy to also treat patients with hemophilia B.
Spark Therapeutics’ data was presented at the 21st Congress of the European Hematology Association (EHA) on June 11th.
In the rare genetic disease hemophilia
, the blood cannot clot properly, leaving affected individuals at risk from excessive bleeding. Mostly males are affected. Hemophilia is caused by a deficiency in specific proteins called clotting factors. These clotting factors participate in the sequence of events that help blood clot in response to injury. Without treatment, even small injuries can be potentially life-threatening. People with severe forms of the condition may spontaneously bleed into their muscles or joints.
Hemophilia A is more common than hemophilia B. The conditions are caused by deficiencies in clotting factors VIII and IX, respectively. There are also even less common forms of hemophilia caused by deficiencies in other clotting factors.
Currently, doctors treat hemophilia with intravenous infusions of clotting factors to control and prevent bleeding episodes. This treatment is not perfect, however. These treatments require repeated infusions. Between treatments, levels of clotting factor may drop too low, making bleeds more likely.
The idea for gene therapy for hemophilia has been around since the 1980s. Conceptually, a viral vector could deliver the corrected gene into cells, allowing them to make the needed clotting protein. But though clinical trials for gene therapy treatments began 15 years ago, no gene therapy treatment has yet made it to market.
Presently, a number of different companies are working to make this therapeutic approach a viable treatment. Spark’s product, SPK-9001, uses an adeno-associated virus to express the factor IX gene in the liver. A similar product, SPK-8011, uses similar technology to express factor VIII. These products do not need to provide normal amounts of these factors to be effective. Notably, keeping factor levels greater than 12% of normal levels
at all times reduces the risk of bleeds.
Gene therapy for hemophilia B
Dr Spencer Sullivan, of the University of Mississippi Medical Center presented the findings from their initial cohort at the EHA Congress. A group of 4 subjects with hemophilia B received a single dose of SPK-9001. Levels of factor activity rose and stabilized at 28% of normal in the first patient, 41% of normal in the second patient, 26% of normal in the third patient, and 33% of normal in the fourth patient. After 58 weeks of observation, none of these subjects needed factor infusions to prevent bleeding.
Notably, none of the patients showed elevation in liver enzymes that would signal liver damage and require immunosuppressive treatment. This is significant, since immune attack on the liver cells producing the factor is a possible concern
in this context.
Gene therapy for hemophilia A
In addition to the clinical data with SPK-9001, Spark Therapeutics also gave an update on the preclinical studies that have underway with SPK-8011 to treat hemophilia A. Katherine A High, MD, co-founder and president of Spark said in a press release, “We remain on track to rapidly progress SPK-8011 for hemophilia A into a Phase 1 /2 trial in the second half of 2016, and to potentially see the first human data from this program in the first half of 2017.” In May, preclinical data presented at the American Society of Gene and Cell Therapy demonstrated factor VIII expression in the range of 15% to 35%.
Jeffrey D. Marrazzo, co-founder and chief executive officer of Spark also spoke to the potential of these treatments. “The clinical data emerging from our hemophilia B program, which is partnered with Pfizer, and the strong parallels to the preclinical data from our rapidly progressing program in hemophilia A, give us early confidence in achieving our goal of eliminating the need for regular infusions to control and prevent bleeding episodes in patients with these diseases through a potentially one-time, intravenous administration of highly optimized gene therapies."