For Rigel, a surprising placebo response spurs a PhIII fail, stock beating. But it's been here before
A California biotech familiar with speed bumps ran into another early Wednesday as it tries to push its only approved drug into another indication.
Rigel Pharmaceuticals reported a Phase III fail for its bleeding disorder drug fostamatinib, saying the primary endpoint did not achieve statistical significance when compared to placebo. The biotech attempted to induce a durable hemoglobin response in patients with warm autoimmune hemolytic anemia, or wAIHA, but came up short due to what execs said were “geographical differences” between the drug and placebo cohorts.

In particular, Rigel observed placebo arm patients in eastern European countries achieve higher rates of durable response than those in the active cohort. A post-hoc analysis showed a statistically significant drug response for American, Canadian, Australian and western European patients, but it’s not yet clear what caused the discrepancy, CMO Wolfgang Dummer said on an investor call Wednesday morning.
Whatever the reason, investors were not thrilled with the final outcome. Rigel shares $RIGL were slashed in half in early Wednesday trading, falling below $1 apiece for the first time.
The biotech is attempting to expand fostamatinib’s footprint into other bleeding disorders after it was approved in 2018 to treat adults with chronic immune thrombocytopenia who failed on previous treatments. Branded as Tavalisse, the drug was being studied in 90 wAIHA patients across the globe.
Overall, researchers randomized the patients 1-to-1 to the drug and placebo groups. Of the 45 individuals taking fostamatinib, 16 saw durable hemoglobin responses, compared to 12 of 45 in the placebo group. Those respective rates, 35.6% and 26.7%, translated to a p-value of p=0.398.
But Rigel execs insisted the placebo response from eastern European patients spurred on the Phase III miss. According to Rigel’s analysis, nine of the 12 placebo responders came from this part of the world.
Asked on Wednesday’s call whether the company found such a placebo response surprising, Dummer answered in the affirmative and blamed the relative lack of other available therapies.
“In eastern Europe, drugs like rituximab are less regularly available, so the patients that are out there are apparently less treatment-experienced, and the sites found the patients that were more recently diagnosed with AIHA,” Dummer said. “Now is that a surprise? I don’t know how anybody would be able to predict what precise patients would enroll in the study, other than saying biologics are less available in eastern European countries.”
Dummer added in response to a follow-up question that the Russian invasion of Ukraine did not affect the study’s results, saying “not one” placebo responder came from either country. Most of the placebo responders came from Bulgaria and the Czech Republic, Dummer said.

Despite the miss in this study, CEO Raul Rodriguez said Rigel is hopeful it can come to an agreement with the FDA on the best path forward for approval. The meeting will likely take place either in the third or fourth quarter this year, he said.
Rigel is no stranger to headwinds, particularly with fostamatinib, as the drug’s earlier road to approval was littered with setbacks. In 2016, a Phase III study for immune thrombocytopenia missed the primary after a patient in the placebo group achieved a response in addition to those taking the drug.
While Rigel’s first Phase III came in statistically significant with a p-value of p=0.03, the other’s single placebo response induced a p=0.26 p-value. But the FDA went ahead with the thrombocytopenia approval, with regulators willing to overlook the miss and make the drug available to patients without an advisory committee.
With Wednesday’s trial harkening back to the 2018 situation, Rodriguez projected confidence that this next FDA go-around would be no different.
“Those patients got a product that was immensely helpful and we believe these [wAIHA] patients deserve no less,” Rodriguez said.