CSL Behring Acquires AMT-061, Hem B Gene Therapy in Phase 3 Trial

CSL Behring has closed an agreement giving it global commercialization and licensing rights to AMT-061, an experimental gene therapy for hemophilia B now being tested in a Phase 3 clinical trial.

The therapy’s developer, uniQure, will receive an upfront cash payment of $450 million from CSL Behring and is eligible for additional royalty payments, as well as up to $1.6 billion if certain regulatory and commercial milestones are met.

uniQure remains responsible for completing the ongoing Phase 3 HOPE-B trial (NCT03569891), assessing the five-year safety and effectiveness of a single dose of AMT-061 in 54 men with moderate-to-severe hemophilia B. The trial is expected to conclude in March 2025.

The company will also scale up manufacturing to ensure commercial access to the therapy.

While announced in June 2020, the deal’s closing was subject to a compliance review with antitrust laws in the U.S., the U.K., and Australia.

“This agreement enables us to take forward a gene therapy that, if approved, has the potential to transform the lives of hemophilia B patients, sharply reducing or eliminating bleeds and routine infusions, life-limiting restrictions, and the constant fear of debilitating injury when blood clotting levels are low,” Paul Perreault, CSL’s CEO, said in a press release.

Matt Kapusta, uniQure’s CEO, added in a separate press release that CSL Behring is an “ideal commercial partner,” allowing AMT-061 “to be made available to the largest number of hemophilia B patients as quickly as possible” upon an approval decision.

“We are excited to embark on our relationship together with a shared goal of delivering this potentially transformative therapy to patients around the world living with hemophilia B,” Kapusta added.

Gene therapy has the potential to be a life-changing treatment for hemophilia B patients.

It works by providing cells with a working version of the mutated, disease-causing F9 gene, thereby increasing the levels of factor IX (FIX), the blood clotting protein these patients are missing. As such, this type of treatment is expected to help patients prevent and control bleeds for long periods of time, possibly for several years.

“Hemophilia B patients live with the knowledge that they are at constant risk of bleeds, and that every bleed can mean that tissue or joints are irreparably damaged,” said Bill Mezzanotte, MD, CSL Behring’s executive vice president, chief medical officer, and head of Research and Development.

“Imagine what it might mean to be freed from that fear, secure in the knowledge that your self-generated FIX levels will be high enough to protect you today, tomorrow, and every day, ideally for years to come,” Mezzanotte added.

Administered directly into the bloodstream, AMT-061 (etranacogene dezaparvovec) uses a modified and harmless version of the adeno-associated virus variant 5 (AAV5) to deliver a highly functional version of the F9 gene, called FIX-Padua, to patients’ cells.

Two-year data from an ongoing Phase 2b trial (NCT03489291) showed that a single dose of AMT-061 led to a stable and sustained FIX activity — with levels reaching up to more than 50% of what would be considered normal — in all three treated men with severe hemophilia B.

The therapy also prevented the occurrence of spontaneous bleeds and the need for replacement therapy in two of the three men, and the need for preventive therapy in all patients.

Top-line results from the Phase 3 HOPE-B study showed that AMT-061 led to a rapid, 36% increase in FIX activity, corresponding to a mean of 37.2% of normal levels, at around six months following treatment.

In all but one man, these improvements occurred regardless of pre-existing FIX inhibitors, or neutralizing antibodies that can limit the therapy’s efficacy.

Participants’ FIX activity levels are set to be measured again at one-year post-dosing (by mid-year) to confirm they have stabilized, as was seen in the previous Phase 2b study.

AMT-061 was generally well-tolerated, with no serious treatment-related adverse events reported to date.

The U.S. Food and Drug Administration (FDA) recently lifted a clinical hold on uniQure’s gene therapy program for hemophilia B, which was put in place after a HOPE-B participant developed hepatocellular carcinoma, a type of liver cancer. The FDA agreed with UniQure’s assessment, based on an independent review, that it was very unlikely the therapy caused this cancer.

Acquisition of AMT-061’s global rights strengthens and expands CSL Behring’s current cell and gene therapy platform and blood-related product portfolio, the company stated, which include among its offerings other treatments for hemophilia B and A.