For severe cases of the bleeding disorder von Willebrand disease, patients must make frequent visits to treatment centers for infusions of the key clotting protein that they lack. Incyte is putting up $1.25 billion to acquire a startup whose late-stage drug candidate offers a much less burdensome dosing regimen. Incyte executives say this drug not only offers the potential to become the new standard of care for von Willebrand, it also diversifies the blood disorder biotech’s pipeline as its top product loses patent protection.
Vega Therapeutics is Incyte’s first acquisition under CEO Bill Meury, successor to longtime Chief Executive Hervé Hoppenot, who retired last year. Speaking during a Monday conference call, Meury said Incyte was attracted to Vega and its drug, VGA039, due to its strong clinical data to date, clear regulatory path, commercial opportunity, and complementary fit.
“VGA039 checks all boxes we look for in a business development opportunity,” he said. “It’s squarely within our core — hematology. The science, the disease, and the R&D and commercial operating models, are all areas where Incyte has real expertise.”
Von Willebrand disease is a bleeding disorder stemming from deficiency or dysfunction of the clotting protein that gives the condition its name. According to the Centers for Disease Control and Prevention, this disease is found in estimated 1% of the U.S. population, which means that if affects about 3.2 million people, making it the most common inherited bleeding disorder. Patients who have it experience bleeding episodes that can be frequent and severe.
For patients whose disease does not adequately respond to desmopressin, a hormone drug that stimulates release of von Willebrand factor, the next treatment option is receiving regular infusions of von Willebrand factor. There are several plasma-derived versions made from human the blood of human donors. Takeda Pharmaceutical’s Vonvendi is the only FDA-approved engineered version of von Willebrand factor. These treatments are administered as intravenous infusions two to three times a week — as many as 156 infusions a year.
Vega’s VGA039 offers the prospect of monthly dosing via a subcutaneous injection that patients can administer themselves. This drug is a monoclonal antibody designed to go after a novel target called Protein S (ProS), a protein that plays a role in two pathways that prevent excessive clotting. By blocking ProS, the Vega drug is intended to restore the balance of clotting proteins in the blood. Von Willebrand disease is the first of what Vega believes is many potential bleeding disorder applications for this drug.
In an open-label Phase 1/2 single-ascending dose study in von Willebrand disease, VGA039 led to clinically meaningful 74% reduction in bleeding rates. All doses of the drug were safe and well tolerated. These results were presented last year during the annual meeting of the American Society of Hematology (ASH). An open-label Phase 3 clinical trial is underway evaluating the drug for preventing bleeding in patients across all types of von Willebrand disease in patients age 12 to 75. After a 24-week observational period free of any prophylactic treatment, participants will proceed to a 49-week active treatment period. The main goal is measuring the frequency of bleeding events; preliminary data are expected in early 2029.
With VGA039, Incyte aims to treat only the most severe cases of von Willebrand disease. While the CDC figures indicate high prevalence of the disorder, just 135,000 U.S. patients are formally diagnosed with the disease, according to Incyte. Of the estimated 35,000 of these patients who are treated in specialty centers, between 7,000 and 10,000 have severe or frequent bleeding — gastrointestinal and mucosal bleeding and bleeding in joints and muscles — making them eligible for prophylactic treatment, said Incyte Chief Strategy Officer Dave Gardner. But the limitations of that prophylactic option mean only an estimated 2,000 patients receive it.
Incyte aims to expand the von Willebrand prophylaxis market by bringing patients a more convenient treatment regimen, Gardner said. This strategy has precedent in another bleeding disorder. In hemophilia A, Roche’s Hemlibra, a subcutaneously injected bispecific antibody, gained favor over frequent infusions of clotting factors, Gardner said. Since its 2017 regulatory approval, Hemlibra has grown to become a blockbuster product.
“We have seen with hemophilia A that when prophylaxis becomes more practical, adoption can become the norm with rates approaching 90% versus only 25% in severe or recurrent von Willebrand disease today,” Gardner said. “There’s a real opportunity to close the gap between those who need prophylaxis and those who are receiving it.”
VGA039 was discovered and developed by Vega, a subsidiary of Star Therapeutics. Star operates a “hub-and-spoke model” in which startups are formed around drug program. Each subsidiary develops its respective drug candidate on its own while sharing in resources from the parent company. Vega launched in 2022 with Star presenting the biotech’s initial preclinical data during the 2022 ASH meeting.
Incyte is established in hematology with four commercialized drugs and additional candidates in its pipeline. Jakafi is Incyte’s top hematology product and the company’s top seller overall, accounting for $3 billion in revenue last year, a more than 10% increase from the prior year. This oral small molecule inhibitor of two JAK proteins is approved for treating myelofibrosis, polycythemia vera, and graft-versus-host disease. But Jakafi faces patent expiration starting in 2028, so Incyte is looking for new drivers of revenue growth.
In an investor presentation, Incyte said it projects VGA039 could generate more than $1 billion revenue in global net sales. But this drug could face competition from Hemab Therapeutics. In April, Hemab went public to support a pipeline that includes the antibody drug HMB-002, which is currently in Phase 2 testing as a prophylactic treatment for von Willebrand disease. William Blair analyst Matt Phipps likes the Vega acquisition. In a research note, he wrote that the Vega drug fits with Incyte’s hematology assets, bringing a relatively de-risked late-stage drug with blockbuster sales potential.
“Management is guiding for the ongoing Phase 3 study to read out in early 2029, leading to a potential launch in 2030, just after the time of Jakafi loss-of-exclusivity,” Phipps said. “Therefore, while this acquisition will not contribute to the first year post-Jakafi, we believe it improves the growth outlook for Incyte into the 2030s.”
The $1.25 billion sum that Incyte is paying to Star is an upfront payment. If VGA039 achieves sales milestones, Incyte could shell out up to $750 million more. The companies expect to close the transaction in the third quarter of this year. As of the end of the first quarter of this year, Incyte reported its cash position was $4 billion. Meury said Incyte still has the financial resources to pursue more deals.
“We’re patient right now,” he said. “If we see something that makes sense, we’ll do it. If not, we’ll wait.”
Public domain image by Flickr user SciTechTrend
