Xconomy Boston

Despite the early and in some cases stunning results produced by gene therapy treatments in handfuls of hemophilia patients, significant questions remain about their durability, safety, and how broadly theyll be used if they are ultimately shown to work. The first human data produced by Dimension Therapeutics, one of several companies developing hemophilia gene therapies, are the latest example.

Shares of Cambridge, MA-based Dimension (NASDAQ: DMTX) tumbled more than 49 percent on Tuesday on early data from a Phase 1/2 trial of DTX101, its experimental gene therapy for hemophilia B.

DTX101 boosted the levels of the blood-clotting protein Factor IX in six patients. Those on the higher of two tested doses havent needed other drugs since getting treatment. But five of the six patientsand all three on the higher of the two tested dosesalso saw a rise in liver enzyme levels, indicating an immune reaction to the gene therapy. While none of the five patients have had any safety problems, the liver enzyme spikes have caused a delay for Dimension. The company wont test an even higher dose of DTX101 in patients until it gets feedback from the FDA.

Gene therapy offers the potential of a long-lasting, if not permanent treatment for hemophilia patients, whodepending on how severe their disease ismay need frequent infusions of preventative drugs to stave off dangerous bleeds. A group of experimental gene therapies have been creeping their way forward in clinical trials, accumulating data in dribs and drabs. Spark Therapeutics (NASDAQ: ONCE) and UniQure (NASDAQ: QURE) are the furthest along in hemophilia B, while BioMarin Pharmaceutical (NASDAQ: BMRN) leads the way in the more common hemophilia A.

Each experimental therapy has shown promise helping patients produce meaningful levels of the clotting proteins Factor IX and Factor VIII, respectivelymore than 5 percent of the levels found in normal patients, which many view as the minimum bar for successover the course of a year or more. And Spark and BioMarin have seen much higher numbers than that, in some cases. But there are caveats: Those results have come in small sample sizes, and they have varied patient to patient. Data today from Dimension show the three patients on a low dose of DTX101 had roughly 3 to 4 percent of normal Factor IX levels a year after treatment. The results are earlier for those on a higher dose: 5 and 8 percent, respectively, for two patients 12 weeks post-treatment; 7 percent for a third patient 7 weeks after DTX101.

Additionally, so far, liver enzyme increases have been seen in clinical tests for each of the hemophilia gene therapies. Such increases could indicate that patients immune systems were attacking their liver cells, which are the ones that take up the therapeutic gene and churn out the new clotting protein. Theyre typically treated with a short course of immunosuppressive steroids and havent caused bad side effects so far. But in some cases theyve stifled a response to gene therapy, which is important because it means that certain gene therapies may not workor at least wont work as well as they couldfor some patients who develop neutralizing antibodies. It also means that patients who develop those antibodies wont be eligible for a second dose if the gene therapy wears off. This phenomenon reduces the potential market for the firms developing hemophilia gene therapies. Such immune responses were the impetus behind a deal Spark cut last year with Selecta Biosciences (NASDAQ: SELB), for example.

We continue to explore the therapeutic window for DTX101 as our data mature and in light of the [liver enzyme] rises that appear to be associated with a decline in [Factor IX] activity, CEO Annalisa Jenkins said in a statement.

Heres more on Dimension, and the technical differences between each of the companies developing gene therapies for hemophilia.

Ben Fidler is Xconomy's Deputy Biotechnology Editor. You can e-mail him at bfidler@xconomy.com

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Investors Sour on Data Debut For Dimension's Hemophilia Gene Therapy - Xconomy