Gene Therapy, Results

Encouraging gene therapy data give uniQure an injection of confidence as it preps PhIII showdown with Spark

Gene therapy company uniQure started the week in style with the news that it’s dosed the first patient in its Phase III trial — a crucial step toward its quest for the best-in-class, first-in-market title in hemophilia B gene therapy. And today it’s offering an update on the kind of mid-stage data it’s armed with.

Matt Kapusta

Mean Factor IX levels hit 38% of normal levels 12 weeks after the three patients tracked in the Phase IIb study received the one-time injection, reaching what the company calls “the normal range” and well above the 12% commonly regarded as sufficient to substantially reduce spontaneous bleeds.

It’s the first look at data three months post-administration — significant because most patients don’t begin to start plateauing until that point, CEO Matt Kapusta tells me in a preview of the results, which follows an upbeat snapshot in November on six-week data.

So have they reached the peak in FIX levels? Probably not, Kapusta said.

The best way to glean that is we actually did a Phase I/II study with the first generation product that is nearly identical to the AMT-061 and included patients that were at the same dose. […] Of the 9 patients that were off of prophylaxis, 8 of them had Factor IX activity that was higher at 52 weeks or — their latest measurement was higher than what it was at 12 weeks. […] So we don’t know if that will continue to be the case, but that’s probably — looking at those kinetics from the Phase I/II study suggests that there is potential for meaningful increases going forward.

Since the patients began dosing at different times, uniQure also gleaned insights into the (slightly) longer term FIX activities: 48% for the first patient at week 16; 25% for the second patient at week 14; and 51% for the third patient at 12 weeks.

“It’s not unusual to have a three, maybe four-fold multiple between your minimum and your maximum,” Kapusta says. “Here of course we’ve got about a two-fold. So in our view the variability is actually tighter.”

The new round of data drew universal applause from analysts, with Chardan speculating that the company is now a prime takeover target. Shares are up 4%.

A chief rival of Spark Therapeutics — which is tapping into hemophilia as a follow-up to its groundbreaking gene therapy for the eye — Lexington, MA- and Amsterdam-based uniQure $QURE pleased investors and analysts back in November when it reported mean FIX levels of 31% at six weeks.

While careful to note that “we don’t love commenting on other people’s data,” Kapusta cited the high levels of FIX activity, low immunogenicity — none of uniQure’s patients have required immunosuppression so far — and the fact that it doesn’t exclude patients with pre-existing antibodies to AAV vectors as reasons to believe that they have a “highly comparable if not potentially an optimized or superior target product profile.”

But the real showdown will take place in the pivotal stage, as uniQure catches up with a Phase III program that Spark partner Pfizer began last summer.

With 20 active sites across the US and Europe, uniQure’s Phase III is expected to enroll 50 patients by the end of the year. Top-line data on the primary endpoint — FIX activity after six months — should be ready in late 2020, paving the way for a BLA submission in 2021, Kapusta said.


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Wren Therapeutics Boston, MA
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Schrödinger New York, NY

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