A year after getting UniQure’s gene therapy, hemophilia patients are still doing better – BioPharma Dive

One year after receiving an experimental gene therapy developed by the Dutch drugmaker UniQure, patients with hemophilia B aren't having nearly as many bleeding issues as they used to have.

In hemophilia, genetic mutations prevent the body from making proteins needed to clot blood. People with the less common, "B" form of the disorder are missing a protein known as Factor IX. UniQure's medicine is meant to provide a working version of the gene so patients can generate their own clotting protein, and rely less or ideally, not at all on so-called replacement factor treatments.

UniQure said Tuesday that, a year after receiving the company's therapy, patients enrolled in the company's HOPE-B clinical trial were experiencing 80% fewer bleeding episodes that require treatment.

At the trial's start, these patients were having an average of three to four bleeding episodes annually. Now, according to UniQure, they're having less than one. The use of replacement factor therapy declined 96% during the 52-week period, as all but two of the 54 participants successfully discontinued their preventive infusions.

What's more, patients had almost 42% the amount of clotting protein typically observed in people who don't have hemophilia B. That's a slight improvement from six-month data presented in December, which showed protein levels at 39% of normal.

Yet, in spite of the positive data, UniQure shares dipped more than 5% in early afternoon trading Tuesday. CSL Behring, which spent $450 million to acquire the rights to UniQure's therapy, also saw its stock trade down.

Some of that stock market reaction may be related to an update Uniqure disclosed alongside the fresh data about the approval process for its therapy. According to UniQure, the Food and Drug Administration primarily wants to see evidence the therapy has a lasting effect, so the agency's focus will be on 52-week data. However, that time frame must start from when patients' protein levels stabilize, rather than from when they first received UniQure's therapy.

The company said all participants in its study achieved steady-state protein levels by week 26. As a result, UniQure is now measuring the study's success by annualized bleeding rates at week 78, with the expectation that patients to complete 78-week follow-up visits by the end of September. That should allow UniQure and CSL to file for approval in first quarter of 2022, months later than when the companies had estimated last year.

If approved, UniQure's gene therapy would become the first cleared to treat any kind of hemophilia. Another, for hemophilia A, was up for approval last year, but the FDA rejected it in in a major surprise. In issuing its rejection, the FDA asked for two years of follow-up data from the therapy's developer, BioMarin Pharmaceutical, a task that can't be completed until November 2021.

Estimates hold there are as many as 33,000 people living with hemophilia in the U.S., with the B form being about four times less common.

Though the FDA has approved around half a dozen drugs to treat hemophilia B, patients taking them can still experience bleeds. Additionally, they can develop a type of antibody called an inhibitor, which blocks the effects of replacement factor.

That's made gene therapy, with its potential as a one-time fix for the disease, an attractive option for some patients and physicians.

Still, concerns remain. UniQure's study was stopped late last year, for example, after researchers saw an unexpected case of liver carcinoma in one participant, reigniting long-held fears about gene therapy's potential to drive cancer.

UniQure investigated the case and recently concluded, along with an independent laboratory and outside experts, that its therapy was "highly unlikely" to have caused the cancer.

There are also worries that gene therapy won't work for everyone. Some people have pre-existing "neutralizing antibodies" that attack the viruses used to deliver functioning genetic material.

UniQure has found its therapy appears, for the most part, to bypass this issue of neutralizing antibodies. The company said Tuesday it hasn't seen any "significant correlation" in how patients who have these antibodies at least to a certain range are responding to its therapy.

UniQure said that range is high enough that it should encompass more than 93% of the general population. The company noted in December how one of the study participants who didn't respond its therapy had neutralizing antibody levels that were five times greater than anyone else in the group.

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A year after getting UniQure's gene therapy, hemophilia patients are still doing better - BioPharma Dive