FDA Approves Drug for Chronic Immune Thrombocytopenia

Tavalisse (fostamatinib) was granted approval by the Food and Drug Administration (FDA) for patients with chronic immune thrombocytopenia (ITP) after they had an insufficiencent response to another therapy. The approval is based on the findings from three trials.

ITP is a condition where the body does not produce enough platelets, eventually affecting the ability of blood to clot. The condition can be caused by cancer treatments — such as chemotherapy and radiation – as well as having hematologic cancers.

In the first randomized study, known as FIT-1, 18 percent of patients treated with Tavalisse experienced a platelet response compared with none in the placebo arm. In the second study, known as FIT-2, a stable platelet response was seen in 16 percent of patients in the Tavalisse group compared with 4 percent treated with placebo. Patients from these trials were could also be included in an open-label expansion cohort (FIT-3). In this study, 23 percent of those who received prior placebo in FIT-1 or -2 had a platelet response to Tavalisse.

"Chronic ITP is challenging to treat because the heterogeneity of the disease makes it difficult to predict how an individual patient will respond to available treatments, and not all patients can find a treatment that works well for them," lead investigator of the FIT clinical trial program James Bussel, M.D., professor emeritus of pediatrics at Weill Cornell Medicine, said in a statement. "The FDA approval of fostamatinib arms physicians with a new treatment option, which works via a novel mechanism."

One hundred fifty patients were enrolled across both double-blind, phase 3 FIT trials. All patients had received prior ITP treatment, which consisted of corticosteroids (94 percent), immunoglobulins (53 percent), thrombopoietin receptor agonists (TPO-RA; 48 percent) or splenectomy (35 percent). Nearly half of patients were on stable concurrent ITP therapy (47 percent). The FIT-3 study included those without a response at 12 weeks and those who completed the full 24 weeks of the double-blind study. Overall, 123 patients enrolled in FIT-3. Of these patients, 44 had received prior placebo and 79 were in a Tavalisse-receiving arm.

The median age of patients enrolled across the double-blind studies was 54 years (range, 20-88). The median time since ITP diagnosis was 8.45 years and baseline platelet counts were 16 x 10⁹ per liter. Overall, 45 percent of patients had platelet counts below 15 x 10⁹ per liter.

Across studies, Tavalisse was started at 100 mg twice daily, with a dose escalation to 150 mg twice daily, based on platelet counts and tolerability. Most patients (88 percent) were dose-escalated at week four or later. The primary endpoint was stable platelet response, which was defined as at least 50 x 10⁹ platelets per liter of blood on at least four of six visits between weeks 14 and 24 of the study.

Among patients receiving a prior TPO-RA, 17 percent had a stable response to Tavalisse, despite the TPO-RA having lost its effect for these patients prior to enrollment. Overall, rescue medication was required by 30 percent of those in the Tavalisse and for 45 percent of patients in the placebo group. Of those responding to Tavalisse, 18 continued to have stable platelet counts for 12 months or longer.

With the increase in platelet counts, there were fewer cases of bleeding experienced by patients in the Tavalisse arm compared with placebo (29 percent vs 37 percent, respectively). Moderate bleeding events were experienced by 9 percent of patients in the Tavalisse arm and by 10 percent for placebo. Severe bleeding events were seen in 1 percent and 6 percent of patients and serious bleeding events occurred in 4 percent and 10 percent of patients in the Tavalisse and placebo groups, respectively.

The most frequently observed all-grade adverse events (AEs) with Tavalisse versus placebo, respectively, were diarrhea (31 percent vs 15 percent), hypertension (28 percent vs 13 percent), nausea (19 percent vs 8 percent), dizziness (11 percent vs 8 percent), ALT increase (11 percent vs 0 percent), respiratory infection (11 percent vs 6 percent), AST increase (9 percent vs 0 percent) and rash (9 percent vs 2 percent).

"We are excited to bring this new medicine to the population of adult patients with chronic ITP in need of additional therapies," Raul Rodriguez, president and CEO of Rigel Pharmaceuticals, the company developing fostamatinib, said in a statement. "This regulatory milestone, our first product approval, validates the therapeutic effect of SYK inhibition in an autoimmune disease."

Rigel Pharmaceuticals plans to have Tavalisse ready for commercial launch in late May 2018.