Baxalta Inc. rang up the second U.S. approval since its official split from Baxter International Inc. with the FDA's nod to Vonvendi (von Willebrand factor [recombinant]). The first therapy approved to treat adults with von Willebrand disease (VWD) – the most common inherited bleeding disorder in the world – gave the Bannockburn, Ill.-based pharma two important therapies in major bleeding disorders. Last month, the FDA green-lighted Adynovate (antihemophilic factor [recombinant], pegylated) to treat hemophilia A. (See BioWorld Today, Nov. 17, 2015.)

A recombinant von Willebrand factor (VWF), Vonvendi preserves ultra-high molecular weight multimers, thought to represent the most active portion of the protein supporting clot formation, explained Brian Goff, Baxalta's executive vice president and president of Baxalta Hematology.

"This is the attribute that many clinicians will say leads to such excellent clinical results," Goff said. "These multimers are not possible in traditional, plasma-derived therapies because they tend to get cut up, or cleaved. In the way we manufacture Vonvendi, we preserve those multimers."

In August, Baxalta reported convincing phase III findings on the therapy, previously known as BAX 111 (vonicog alfa). All participants reported successful treatment of bleeding episodes, with 96.9 percent of treated bleeds (N=192 bleeds in 22 patients) rated as "excellent" on efficacy and the remainder as "good." Most bleeds (81.8 percent) were resolved with a single infusion, and the treatment showed a mean half-life of 21.9 hours (± 8.36). (See BioWorld Today, Aug. 4, 2015.)

No thrombotic events or severe product-related adverse events were observed during the clinical trial, nor were there treatment-related binding or neutralizing antibodies against VWF or neutralizing antibodies against factor VIII (FVIII). The most common adverse reaction observed in greater than 2 percent of patients in clinical trials was generalized pruritus.

Vonvendi also is the first U.S. treatment that contains only trace amounts of FVIII, allowing for more customized treatment options when patients don't require additional FVIII, according to Baxalta.

Although VWD affects up to one in 100 people worldwide, the condition is woefully underdiagnosed and undertreated, Goff said, with just 16,000 patients – those considered the most severe – on therapy. The genetic disorder causes alterations or deficits in VWF that result in impaired clotting, affecting women and men equally. The disease can manifest through a variety of bleeding events, including mucosal bleeds, gastrointestinal bleeds and menorrhagia.

Previous treatments for VWD were largely limited to the plasma-derived therapies Wilate (Octapharma USA Inc.) and Humate-P (CSL Behring LLC), which had their own dust-up several years back over the FDA's take on orphan drug exclusivity. (See BioWorld Today, Aug. 10, 2012.)

Although the label was limited to on-demand treatment of VWD in adults 18 or older, "that's by no means the finishing point for Vonvendi," Goff maintained. "We have an ambitious plan to continue to enhance the label."

Baxalta will seek to include surgical patients and a pediatric indication while it pursues ex-U.S. approval, especially in the EU, where the company expects regulatory filings in 2017. The company also will look at the opportunity for Vonvendi in related indications, such as acquired VWD and other platelet-related disorders, according to Goff.

'FRAGILE COMMUNITY THAT HAS HAD VERY LITTLE ATTENTION'

As for the U.S., "this is a fragile community that has had very little attention," Goff told BioWorld Today. "We're quite thoughtful about how we can ensure the appropriate engagement with the community."

Translation: There's work to be done on physician and patient education before the Vonvendi launch, expected in the latter part of 2016.

"As we get closer, we'll determine the exact launch timing," Goff said. Pricing will be disclosed at that point, he added.

Baxalta plans an extensive outreach program to present Vonvendi as "the new standard of care," encompassing meetings with key opinion leaders, clinicians in hemophilia treatment and related centers, and organizations such as the National Hemophilia Foundation and local patient advocacy groups.

"Unlike hemophilia, where there are well-organized communities, both nationally and locally, with von Willebrand disease, it's pretty scattered," Goff said. "A lot of these patients are isolated and, I would say, silently suffering. They may not even, in fact, know they have the disease."

Baxalta also wants to ensure adequate product supply prior to Vonvendi's launch, he added.

Baxalta was launched with a clear mission to tighten its grip on global hemophilia and related markets pursued by the previously integrated Baxter. (See BioWorld Today, March 28, 2014.)

The pharma spinout took with it the portfolio of recombinant and plasma-based proteins to treat hemophilia and other bleeding disorders, including market leader Advate [antihemophilic factor (recombinant) plasma/albumin-free method, or octocog alfa)] in hemophilia A and the long-acting follow-on version, BAX 855, using pegylation technology from Nektar Therapeutics Inc., that was approved last month as Adynovate.

So far, Baxalta is executing on all fronts, although success of the educational outreach may determine the ultimate commercial opportunity for Vonvendi. Cowen and Co. analyst Christopher Hamblett predicted "a slow, gradual launch for Vonvendi as Baxalta will have to develop this underpenetrated market and need for a recombinant factor replacement therapy in this market vs. plasma-derived agents, which work well in this setting for on-demand therapy."

Though reluctant to make hard forecasts without pricing info, Hamblett projected U.S. sales of approximately $15 million in 2016 and $30 million in 2017, noting that the market represents roughly 35 percent of the global opportunity in treating VWD.

To that broader market, Hamblett forecast sales of nearly $150 million in 2020, "which could prove to be conservative if BXLT can develop this treatment market more rapidly," he noted, adding, "We expect Vonvendi to achieve peak annual sales of $300-400 million once all indications (prophylaxis, surgical, pediatric populations) and geographies capture the full market opportunity."

Vonvendi's approval was enough to move the needle on Baxalta's shares (NYSE:BXLT), which inched up 20 cents Wednesday to close at $37.21.

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