February 1, 2017
By Alex Keown, BioSpace.com Breaking News Staff
CAMBRIDGE, Mass. – Shares of Dimension Therapeutics plunged more than 60 percent Tuesday night after the company revealed interim data results from its Phase I/II hemophilia B study that showed questionable safety issues regarding its therapy.
Although DTX101, Dimension’s lead AAV (adeno-associated viral) candidate, demonstrated positive results in blood-clotting in two patient cohorts, some patients showed signs of liver toxicity. The reports of elevated liver toxins were enough to spook investors. Share prices plunged from its closing price of $4.25 to $2.15. The fall continued this morning, with prices dropping to $1.90 as of 11:30 a.m.
DTX101 is designed to deliver stable expression of blood clotting Factor IX (FIX) in patients with hemophilia B, a rare genetic bleeding disorder resulting from a deficiency in FIX. Patients received serotype AAVrh10 vector with a codon-optimized FIX gene expressing wild-type FIX protein. Interim data from the first two cohorts showed positive post-treatment follow-ups from six to 52 weeks. All patients in both cohorts improved from moderate/severe-to-severe to either moderate or mild range in terms of factor levels based on World Federation of Hemophilia (WFH) criteria, Dimension said in its statement.
According to the WFH, people with FIX levels of 5 percent or more usually bleed only as a result of surgery or major injury, do not bleed often and, in fact, may never have a bleeding problem, Dimension said.
However, five of the six patients treated with DTX101 experienced elevations in the enzyme alanine aminotransferase (ALT). Dimension said one patient in the second cohort experienced a grade 4 adverse event due to the elevated levels of ALT. A grade 4 event is considered disabling or life-threatening. The patients were treated with corticosteroids, which returned ALT levels to normal in all but one of the patients by the end of January, the company said. The one patient that had not seen a return to normal levels continues to undergo treatment, Dimension said.
Annalisa Jenkins, chief executive officer of Dimension, said the company is 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,” Jenkins said in a statement.
DTX101 has received orphan drug designation from U.S. Food and Drug Administration and the European Commission. In 2013, the World Federation of Hemophilia estimated there were more than 28,000 hemophilia B patients worldwide, including 4,000 patients in the United States.
