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|Dimension Announces Interim Topline Results from Ongoing Phase 1/2 Clinical Program for DTX101, Dimension’s Lead AAV Product Candidate in Development for Adult Patients with Moderate/Severe to Severe Hemophilia B|
Evidence of High-Efficiency Liver Transduction with AAVrh10 Vector
Sub-clinical, Asymptomatic Elevations of ALT Observed in 5 of 6 Patients
In the phase 1/2 study, patients received serotype AAVrh10 vector with a codon-optimized FIX gene expressing wild-type FIX protein. Evidence of efficient liver transduction of DTX101 was observed across the two patient cohorts. Patients in the second dose cohort achieved peak FIX expression of 13%, 20%, and 12% at weeks 4, 8, and 8, respectively. FIX activity was 5% and 8% in two patients at 12-weeks follow-up, and 7% for the third patient at 7 weeks. For the low-dose cohort, expression levels achieved 10-11% peak activity, stabilizing between 3-4% at last follow-up (weeks 24, 48, and 52). The findings in the low-dose cohort are comparable to results published by Nathwani et al in the New
Elevations in alanine aminotransferase (ALT) were observed in 5 of 6 patients with patient 3 in Cohort 2 experiencing a grade 4 adverse event due to an elevated laboratory ALT (defined as >800 IU/L). All elevated liver enzymes were clinically asymptomatic with no elevations of gamma-glutamyl transferase (GGT), alkaline phosphatase or bilirubin, and no patients experienced a drug related serious adverse event (SAE) as of the
“We are encouraged by the apparent efficiency of gene transduction and the early trend we are seeing in sustained FIX activity across both cohorts with our wild-type FIX AAVrh10 vector in patients. We continue to explore the therapeutic window for DTX101 as our data mature and in light of the ALT rises that appear to be associated with a decline in FIX activity,” said Dr.
As the company pipeline and platform progresses, a broad program of translational research, conducted in partnership with the
DTX101 has received orphan drug designation from
*Information sourced from
About Hemophilia B
Hemophilia B is a rare genetic bleeding disorder resulting from a deficiency in FIX. The current standard of care, chronic replacement of FIX protein through routine intravenous infusion, often does not achieve sustained, durable FIX expression, potentially putting patients at risk for spontaneous bleeds and long term joint destruction. In 2013, the
About the Hemophilia B Phase 1/2 Program
Dimension’s phase 1/2 clinical trial of DTX101 is a single arm, open-label, multi-center study, designed to evaluate the safety, dose, and early efficacy of DTX101 in adult patients with moderate/severe to severe hemophilia B. Patients enrolled in Cohorts 1 and 2 range in age from 28 to 70 years, demonstrating baseline FIX expression of ≤2% 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.
Additional information about Dimension’s Phase 1/2 study of DTX101 may be found at ClinicalTrials.gov, using Identifier NCT: NCT02618915.
For more information, please visit www.dimensiontx.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the development, preclinical and clinical results, and the continued progress of Dimension's portfolio and programs, including the initiation, timing, scope, or likelihood of regulatory filings and approvals, and our ability to develop and advance product candidates into, and successfully complete, clinical studies. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include the risks that Dimension’s product candidates, including its candidates, DTX101 and DTX301, will not successfully be developed or commercialized in the times indicated or at all; the impact of the observed data in Cohorts 1 and 2, including the adverse event described above and any later safety event on timing, dosing, regulatory action or patient enrollment with respect to DTX101 and DTX301; and the risks described under the caption "Risk Factors" in Dimension Therapeutics’ Quarterly Report on Form 10-Q for the quarter ended