UniQure, the Netherlands-based biotechnology company, intends to formally ask the Food and Drug Administration to approve its for Huntington’s disease gene therapy now that the two parties are more aligned on the closely watched treatment.
UniQure said Wednesday that, during a recent meeting, FDA staff agreed three years of data gathered from a key trial of the therapy would be enough to support an approval application. As such, the company expects to file one sometime between July and the end of September. The FDA has requested another trial be conducted to confirm the treatment’s effects and, according to the UniQure, the agency wants to make sure both sides see eye to eye on this study’s design before a marketing application gets submitted.
The update is a major about-face for the FDA and a reflection of recent changes in its leadership. Marty Makary resigned as commissioner in mid-May, just days before the firing of Tracy Beth Høeg, who served as acting director of the agency’s main drug review division. Those shake-ups came a little over two months after Vinay Prasad, who oversaw the office that regulates vaccines and gene therapies, departed the FDA for a second time.
Prasad played a particularly important role in what would became a winding, highly publicized saga for UniQure’s “AMT-130” therapy. An oncologist by training, Prasad had been a staunch critic of the ways in which the FDA had tried to expedite the review of certain genetic medicines. Some speculated that, as UniQure received unexpected pushback from the agency, Prasad was either directly or tangentially involved.
UniQure first disclosed plans to file for approval last fall, based on new findings from that key trial. There, researchers evaluated two different dose levels of AMT-130 in 29 participants and compared their disease trajectory to an external control group of similar people in a large, observational study. Results showed that, among 12 patients given the higher dose, signs of disease progression had slowed by 75% after three years.
The data thrilled the Huntington’s community. Investors were equally impressed, as UniQure’s share price more than tripled on the news. The company’s chief medical officer said the findings “reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington’s.”
UniQure leadership was therefore surprised when FDA staff, in a meeting not long after, didn’t view those results as adequate enough to support approval. UniQure noted how that was a “key shift from prior communications.”
From there, the outlook for AMT-130 continued to dim. In late February, during an appearance on CNBC, Makary sought to defend his agency’s approach to approving rare disease therapies. But some investors interpreted certain comments he made as critical of AMT-130 specifically, leading UniQure shares to fall more than 30%.
The following week, UniQure affirmed that FDA staff still had issues with the evidence gathered in its study — the use of an external control group, for example — and “strongly recommended” the company conduct another trial with a control group that receives a “sham surgery.” One Wall Street analyst described this update as the “worst case scenario for many investors.”
The controversy hit a head a few days later, when the FDA took the highly unorthodox step of holding a call between journalists and a high-ranking agency official who spoke about UniQure’s case on the condition of anonymity.
Subsequent reports detailed how the official panned AMT-130 and accused UniQure of mischaracterizing its talks with the agency. Many speculated Prasad was the anonymous source. Congressman Jake Auchincloss, D-Mass., posted on social media that Prasad had, in discussing the case, violated agency rules and federal law. Hours later, Makary confirmed Prasad would be leaving the agency in April, as he’d finished the work he set out to accomplish.
To analysts, UniQure’s announcement Wednesday was a positive sign not only for AMT-130, but other developers who hit unexpected roadblocks from the FDA.
“We think this is great news for [UniQure] and may suggest that the pendulum between regulatory leniency vs inflexible scientific rigor is swinging back to the former now that Vinay Prasad and Marty Makary have left the FDA,” wrote analysts at RBC Capital Markets in a note to clients.
In their own note, William Blair analysts wrote that the change of heart toward UniQure and another drugmaker, Replimune, suggests the current FDA, “largely in caretaker mode, appears to be more flexible on regulatory paths for applications where concerns were previously raised.”
UniQure shares surged nearly 80%, to about $48 apiece, by mid-day Wednesday.
