Rare Daily Staff

Spark Therapeutics and Pfizer said all 15 participants in the ongoing phase 1/2 clinical trial of their experimental gene therapy SPK-9001 for severe or moderately severe hemophilia B had discontinued routine infusions of factor IX concentrates.

Hemophilia is a rare genetic bleeding disorder due to a deficiency in one of several blood clotting factors. People with hemophilia are at risk for excessive and recurrent bleeding from modest injuries, which have the potential to be life threatening. In severe cases, people with the condition can bleed spontaneously into their muscles or joints. In rare cases, they can bleed into the intracranial space, where bleeding can be fatal.

People with hemophilia B lack clotting factor IX. Patients today are treated with intravenous infusions of either plasma-derived or recombinant factor IX to control and prevent bleeding episodes. SPK-9001 is an experimental gene therapy that enables the body to produce factor IX.

“We are pleased to see all 15 participants, notably including the first four participants who have been followed for more than two years, continue to show that a single administration of SPK-9001 has resulted in dramatic reductions in bleeding and factor IX infusions, with no serious adverse events,” said Katherine High, president and head of research & development at Spark.

Based on histories of the trial participants for the year prior to the study, the overall annual bleed rate for all 15 participants was reduced by 98 percent (calculated based on data after week four; 97 percent based on data after infusion) to an annual rate of 0.2 bleeds per participant, compared to an annual rate of 8.9 bleeds before SPK-9001 administration. Only one participant experienced a bleeding event four or more weeks after SPK-9001infusion.

Overall annual infusion rate was reduced by 99 percent (calculated based on data after week four; 99 percent based on data after infusion) for all 15 participants to an annual rate of 0.9 infusions, compared to an annual rate of 57.2 infusions before infusion.

There have been no serious adverse events, no thrombotic events, and no factor IX inhibitors developed. Two participants, one having received SPK-9001 manufactured using an enhanced process, reported related adverse events of elevated transaminases, an indicator of liver injury, and were treated with a tapering course of oral corticosteroids.

The events were asymptomatic, and one event has been resolved, as of the May 7, 2018 data cutoff. One additional participant received a tapering course of oral corticosteroids for an increase in liver enzymes (not exceeding the upper limit of normal) temporally associated with falling levels of factor IX activity.

The companies released the data ahead of a presentation at the World Federation of Hemophilia World Congress in Glasgow, Scotland.

In December 2014, Spark Therapeutics and Pfizer entered into a collaboration that included SPK-9001. Under the collaboration Spark is responsible for conducting all phase 1/2 studies for any product candidates, while Pfizer will assume responsibility for pivotal studies, any regulatory activities and potential global commercialization of any products that may result from the collaboration.

Spark said it has completed enrollment in the phase 1/2 clinical trial of SPK-9001 in hemophilia B and expects to complete the transition of the program to Pfizer this summer. Additionally, Spark said it expects to deliver a batch of drug substance to Pfizer, enabling Pfizer to begin a phase 3 clinical trial.

May 22, 2018
Photo: Katherine High, president and head of research & development at Spark Therapeutics