The SYK inhibitor fostamatinib did not meet the primary endpoint in a phase 3 study of adults with chronic/persistent immune thrombocytopenia (ITP), according to Rigel Pharmaceuticals, Inc., the company developing the drug.
However, fostamatinib did meet that endpoint—a significantly higher incidence of stable platelet response compared to placebo—in an identical phase 3 study.
The combined data from both studies—known as FIT 1 and FIT 2—suggest fostamatinib confers a benefit over placebo.
Therefore, Rigel Pharmaceuticals is still planning to submit a new drug application for fostamatinib to the US Food and Drug Administration (FDA) next year, pending feedback from the agency.
“We believe that the totality and consistency of data from the FIT phase 3 program . . . strongly supports a clear treatment effect, with a sustained clinical benefit of fostamatinib,” said Raul Rodriguez, president and chief executive officer of Rigel Pharmaceuticals.
“We are encouraged by these results and believe that the risk/benefit ratio for fostamatinib is positive for patients with chronic/persistent ITP . . . . As a result, we will continue to pursue this opportunity. Our next step is to seek feedback from the FDA.”
About the FIT studies
Rigel’s FIT program consists of 2 identical, multicenter, randomized, double-blind studies of approximately 75 adults each—FIT 1 (Study 047) and FIT 2 (Study 048).
The patients enrolled in each study had been diagnosed with persistent or chronic ITP, had failed at least 1 prior therapy for ITP, and had platelet counts consistently below 30,000/uL of blood.
In both studies, patients were randomized in a 2:1 ratio to receive either fostamatinib or placebo orally twice a day for up to 24 weeks.
Patients were subsequently given the opportunity to enroll in an open-label, long-term, phase 3 extension study (Study 049), which is ongoing.
Patient characteristics
In FIT 1, 51 patients were randomized to fostamatinib and 25 to placebo. The median age was 57 in both treatment arms. The duration of ITP was 7.5 years (range, 0.6-53) in the fostamatinib arm and 5.5 years (range, 0.4-45) in the placebo arm.
Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 100%), rituximab (51% and 44%), thrombopoietic agents (50% and 60%), and splenectomy (39% and 40%).
The median platelet count at baseline was 15,000/uL in the fostamatinib arm and 16,000/uL in the placebo arm.
In FIT 2, 50 patients were randomized to fostamatinib and 24 to placebo. The median age was 50 in both treatment arms. The duration of ITP was 8.8 years (range, 0.3-50) in the fostamatinib arm and 10.8 years (range, 0.9-29) in the placebo arm.
Prior treatments (in the fostamatinib and placebo arms, respectively) included steroids (90% and 92%), rituximab (16% and 13%), thrombopoietic agents (40% and 42%), and splenectomy (28% and 38%).
The median platelet count at baseline was 16,000/uL in the fostamatinib arm and 21,000/uL in the placebo arm.
Efficacy
The primary efficacy endpoint in both studies is a stable platelet response, which is defined as achieving platelet counts greater than 50,000/uL of blood for at least 4 of the 6 scheduled clinic visits between weeks 14 and 24 of treatment.
In FIT 1, the rate of stable platelet response was significantly higher in the fostamatinib arm than the placebo arm—18% (n=9) and 0%, respectively (P=0.026).
In FIT 2, however, the difference in stable platelet response between the 2 arms was not significant—18% (n=9) and 4% (n=1), respectively (P=0.152).
When the data from FIT 1 and FIT 2 are combined, the response rate is significantly higher in the fostamatinib arm than the placebo arm—18% (18/101) and 2% (1/49), respectively (P=0.007).
The response rate is significantly better in the fostamatinib arm across all subgroups, regardless of whether patients had prior splenectomy, prior exposure to thrombopoietic agents, or baseline platelet counts above or below 15,000/uL.
In the combined dataset, patients who met the primary endpoint had their platelet counts increase from a median of 18,500/uL at baseline to more than 100,000/uL at week 24 of treatment.
In addition, patients who met the primary endpoint had a timely platelet response, and that response was enduring, according to James B. Bussel, MD, a professor at Weill Cornell Medicine in New York, New York, principal investigator on the FIT phase 3 program, and a member of Rigel’s advisory/scientific board.
“The FIT phase 3 studies have both demonstrated that fostamatinib provided a robust and enduring benefit for those patients who responded to the drug,” he said.
Safety
In FIT 1, the overall incidence of adverse events (AEs) was 96% in the fostamatinib arm and 76% in the placebo arm. The incidence of serious AEs was 16% and 20%, respectively. And the incidence of treatment-related AEs was 77% and 28%, respectively.
AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (nausea, diarrhea, vomiting, abdominal pain; 61% and 20%), nausea (29% and 4%), diarrhea (45% and 16%), infection (33% and 20%), hypertension during visit (35% and 8%), and transaminase elevation (22% and 0%).
In FIT 2, the overall incidence of AEs was 71% in the fostamatinib arm and 78% in the placebo arm. The incidence of serious AEs was 10% and 26%, respectively. And the incidence of treatment-related AEs was 39% and 26%, respectively.
AEs (in the fostamatinib and placebo arms, respectively) included gastrointestinal complaints (22% in both arms), nausea (8% and 13%), diarrhea (18% and 13%), infection (22% in both arms), hypertension during visit (20% and 17%), and transaminase elevation (6% and 0%).
