ORLANDO, Fla.—With dosing underway in a pivotal phase 3 trial, Star Therapeutics is illuminating the clinical potential of its anti-bleeding antibody VGA039. In a phase 1/2 trial in von Willebrand disease (VWD), the molecule substantially reduced bleeding in eight patients.
“We're seeing significant reductions in bleeds across all types of VWD and all types of bleeds,” Star founder and CEO Adam Rosenthal, Ph.D., told Fierce Biotech at the American Society of Hematology (ASH) conference in Orlando, Florida. “Serious GI bleeds, joint muscle bleeds, nosebleeds, mouth bleeds, really the whole diversity of bleed types that manifest in VWD.”
Star presented the results at ASH on Dec. 6 and put out a press release on the same day.
Bleeding reductions ranged from 73% to 87% in four VWD patients with similar annual bleeding rates as the patients currently being enrolled in the phase 3 Vivid-6 trial, Rosenthal said. If that mark is matched in phase 3, it would clear the field’s established 50% bar for regulatory approval, he added.
The once monthly self-given injections of VGA039 were well tolerated, with safety data available for all 16 patients in the cohort. Efficacy data were only presented for the eight patients who had completed the treatment regimen. All of those patients have since transitioned to an open-label extension arm of the trial.
“This dataset is compelling, encompassing a diverse patient population across multiple VWD types, a full spectrum of bleed profiles and individuals transitioning from prior prophylaxis regimens,” Steven Pipe, M.D., a pediatrician and pathologist at the University of Michigan, said in Star’s release. “VGA039 has the potential to improve outcomes for all patients with VWD.”
VWD is the most common bleeding disorder, caused by genetic mutations that make patients produce not enough functional von Willebrand factor, a protein needed for blood clotting. Prophylaxis, where patients are infused with the needed factor once or more each week, is the standard-of-care treatment for patients at risk of serious bleeds; an example is Takeda’s Vonvendi, which is also used to directly treat bleeding episodes and prevent bleeding during surgery.
One patient in Star’s trial was receiving factor infusions daily but still “bleeding like crazy,” Rosenthal said. When switched onto VGA039, “we saw 75% to 100% reductions in their bleeding rate compared to their prior prophylaxis.”
“The fact that we can actually be better than standard of care was a huge upside that we weren’t anticipating,” Rosenthal said.
Rather than trying to replace von Willebrand factor, VGA039 is designed to target a different protein, protein S.
Protein S is a natural anticoagulant that works to combat blood clotting. By targeting it, VGA039 is designed to make it easier for blood clots to form, preventing the frequent bleeding that characterizes VWD.
Star is shooting to enroll about 60 patients in its phase 3 trial and announce the results in 2028, Rosenthal said. After that, the CEO is confident that even as a small company, Star can commercialize VGA039 should it be approved.
That’s because, while the asset has a potentially multibillion-dollar market, the cost of getting it to market is relatively low, Rosenthal explained, because the pivotal trial is enrolling so few patients. And many patients with VWD in the U.S. are treated in a hemophilia treatment center, and there are fewer than 150 of those.
“We can easily do this on our own,” Rosenthal said. “We feel really good about that.”
Because of VGA039’s mechanism of action, it could prove beneficial in other bleeding disorders as well, and Star is determined to expand into new indications. The biotech has enough cash to last for a couple of years thanks to a $125 million series D in September.
Historically, VWD hasn’t gotten as much attention as fellow bleeding disease hemophilia A, even though the latter affects fewer patients, Rosenthal said. He welcomes more competition, as it can only benefit patients, while also hailing the hematology community’s recently invigorated focus on noncancerous blood diseases.
“For a long time, there was much more focus on the malignant,” he said. “In the last five to 10 years, the nonmalignant is growing quite a bit. And we heard that from investors.”