Dimension Therapeutics‘ gene therapy candidate drug DTX101 shows promising results by improving the levels of blood clotting factor IX (FIX) in adult patients with moderate/severe to severe hemophilia B, the company said.
Hemophilia B is caused by FIX deficiency, due to mutations on the gene that encodes this protein. Treating and managing hemophilia B’s symptoms requires restoring FIX levels in the blood. However, current strategies for doing so are not very efficient and require constant treatment administrations as a prophylactic approach.
To address the problem, Dimension has designed its DTX101 to deliver and promote stable expression of FIX in such patients. The drug is based on an advanced mammalian adeno-associated virus (AAV) gene delivery technology, or AAVrh10.
DTX101 is currently being tested in a Phase 1/2 clinical trial (NCT02618915) for safety and dose finding. The trial is recruiting participants.
Dimension’s trial is a single arm, open-label, multi-center study. Patients enrolled in Cohorts 1 and 2 range in age from 28 to 70 years, demonstrating baseline FIX expression of 2 percent or less that requires either prophylactic or on-demand recombinant FIX transfusion. Dimension is continuing to explore underlying demographics and patient characteristics to optimize dosing of DTX101.
In January 2017, the company completed dosing in the first two cohorts receiving different doses of DTX101. All patients showed improved levels of FIX during post-treatment follow-up. This led to an improvement from moderate/severe to severe to either moderate or mild-range hemophilia B based on World Federation of Hemophilia criteria.
In addition, patients who received higher doses of the treatment did not require prophylactic or on-demand recombinant FIX transfusion for spontaneous bleeds after treatment. This suggests that this treatment can achieve until-now unmet needs of hemophilia patients.
“The encouraging clinical data from Dimension’s lead program are supported by what we have seen in our patients who participated in the study, many of whom have anecdotally related the positive impact of therapy on their well-being,” Steven Pipe, MD, pediatric medical director of the University of Michigan’s Hemophilia and Coagulation Disorders Program at C.S. Mott Children’s Hospital, said in a press release. “These data add to the growing body of evidence that restoration of clotting function may be achieved by gene therapy.”
However, upon DTX101 treatment, five of six patients in the trial showed increased levels in their blood of a liver enzyme called alanine aminotransferase, or ALT, which can indicate of liver damage. Administration of corticosteroids to efficiently control this adverse treatment and reduce ALT levels is being given throughout follow-up.
As stipulated in the trial’s protocol, the company intends to further test this treatment with even higher doses of DTX101.
“We also continue to explore options for DTX101 as our data mature, while remaining laser-focused on maximizing the value of our portfolio,” said Dimension CEO Annalisa Jenkins. “We are dedicated to advancing these and other key programs in order to bring hope to patients and their families living with rare genetic diseases associated with the liver.”