WIL-31: Expanding treatment options for VWD

On December 1, 2023 the US Food & Drug Administration (FDA) granted expanded approval to Octapharma's von Willebrand factor (VWF), making it the first von Willebrand factor concentrate indicated for prophylactic treatment across all forms of von Willebrand disease (VWD).

The expanded indication is the product of WIL-31, the largest ever prospective prophylaxis study in VWD. Launched by Octapharma in 2020 and completed in November 2022, WIL-31 was a prospective, non-controlled, international, multi-centre phase III trial that investigated the efficacy and safety of Octapharma's von Willebrand factor prophylaxis over 12 months in people aged six and older with severe VWD of any type.

VWD is a rare bleeding disorder that affects up to 1% of the US population, around 3.3 million people. While prophylactic treatment is the standard of care in some bleeding disorders, such as haemophilia A, that is not currently the case for VWD. The label expansion thus offers an invaluable new treatment option for a significant number of patients.1

Exceptional challenges

The rarity of VWD made it particularly difficult for Sylvia Werner, Senior Directorr Clinical R&D, Haematology, who led the study, and her team to recruit patients who met the inclusion criteria for the study. The team had to identify and enrol patients across various age groups and with various types of VWD to receive a broad indication for the product label.

To overcome this, the project team expanded the study to include patients from around the world, including from Lebanon, Ukraine, Russia, Belarus, Hungary, Bulgaria, Croatia and the USA.

Beyond the standard recruitment challenges, the study was impacted by world events that were neither predictable nor controllable. “The start of the WIL-31 study coincided with the start of the COVID-19 pandemic, which posed particular challenges for logistics and operations in all of the countries involved,” recalls Sylvia.

The team also had to ensure that patients were able to make regular visits to the clinic, that blood sampling kits were sent to study sites in time for these visits, and that blood samples were returned quickly to central laboratories in the USA and Germany for testing. During this period, logistical supply chains broke down and shipments were extremely delayed. Sourcing material needed for building blood sampling kits was a particular challenge.

“In addition, the majority of our patients were enrolled in Lebanon, which was hit hard by a financial crisis and fuel shortages, making it difficult for patients to visit the clinics,” explains Sylvia. “Taxi rides from patients’ homes to hospitals cost up to $800 during that time.”

“Last but not least,” remembers Sylvia, “the study was still ongoing in Ukraine when the war broke out and for a short period of time it was unclear what had happened to our patients, our investigators, the study documents and the study drug that was still stored in the country.”

Collaboration is key

Looking back, Sylvia notes that good communication, flexibility and perseverance, as well as motivating her team in times of crisis and recognising their strengths, were the most effective ways of overcoming these unprecedented challenges and bringing the project to a successful conclusion.

“The FDA inspections and data review went smoothly, and we received a broad indication for prophylaxis treatment in VWD that puts us ahead of our competitors, which is very exciting,” explains Sylvia. “And knowing from the outset that we are working to improve the quality of life of our patients is especially rewarding.”

“ The FDA inspections and data review went smoothly, and we received a broad indication for prophylaxis treatment in VWD that puts us ahead of our competitors, which is very exciting.”

Real hope

“Long-term prophylaxis with VWF concentrate, as compared with ondemand treatment for bleeding, is recommended for patients with severe VWD. The findings from WIL-31 provide strong evidence to support the use of VWF prophylaxis and have led to the recent addition of wilate® prophylaxis as a therapeutic indication for VWD in the USA, widening its access to the US patient population,” explains Shveta Gupta MD, a specialist in paediatric haematology and oncology at the Haley Center for Children’s Cancer and Blood Disorders at Orlando Health Arnold Palmer Hospital for Children, Orlando, Florida.

Efficacy was assessed in 33 adult and paediatric VWD patients aged six years and older from 14 centres in eight countries, with patients receiving Octapharma's von Willebrand factor prophylaxis two or three times weekly for 12 months. All patients had taken part in a prospective six-month run-in study (WIL-29) during which they received on-demand treatment with any available VWF concentrate, allowing assessment of the efficacy of prophylaxis at an intra-individual level.

The primary endpoint of the study, a greater than 50% reduction in mean total annualised bleeding rate (ABR) during von Willebrand factor prophylaxis compared with prior on-demand treatment, was met.

In fact, the primary endpoint of the study was met with an 84% reduction in the mean total annual bleeding rate (ABR) compared with on-demand treatment during the previous study. The median spontaneous ABR decreased by 95%. Importantly, no serious drug-related adverse events or thrombotic events were observed during the study.

Empowering patients

Putting patients at the centre of its activities has always been a top priority for Octapharma, where clinical trials and studies have long been directed towards reducing high levels of unmet patient need.

Looking back after the FDA approval, Sylvia says that the most motivating part for her personally was working with a team and with colleagues who enjoy what they are doing as much as she does. “Never give up, even and especially in difficult times. The greater the challenges that are being overcome, the more rewarding the outcome is,” she says.

“The approval of Octapharma's von Willebrand factor for VWD prophylaxis could improve the quality of life for many patients and I’m proud to have led the team that achieved that.”

“Never give up, even and especially in difficult times. The greater the challenges that are being overcome, the more rewarding the outcome is.”

References:

1. Centers for Disease Control and Prevention website, What is von Willebrand Disease?, accessed Nov. 27, 2023