The US Food and Drug Administration (FDA) has granted orphan drug designation to the SYK inhibitor fostamatinib as a treatment for patients
with chronic immune thrombocytopenia (ITP).
Fostamatinib (also known as R935788 or R788) has been shown to increase platelet counts in patients with chronic ITP.
The drug, which comes in tablet form, is thought to prevent macrophages from destroying platelets by inhibiting SYK activation.
Fostamatinib previously produced promising results in a phase 2 trial of ITP patients and is now under investigation in a pair of phase 3 trials (NCT02076412 and NCT02076399).
Results from these trials are expected in mid-2016, according to Rigel Pharmaceuticals, Inc., the company developing fostamatinib.
Phase 2 trial
The trial included 16 adults with chronic ITP. Fostamatinib doses began at 75 mg and were increased until a patient experienced a persistent response, toxicity occurred, or the patient reached the maximum dose—175 mg twice daily.
Eight patients achieved persistent responses. They maintained platelet counts above 50,000/mm3 on a median of 95% of study visits and were able to avoid receiving other treatments.
Four other patients experienced transient responses. They had an increase in platelet count from a median minimum of 17,000/mm3 at baseline to a median maximum of 177,000/mm3.
In all 12 responders, the median platelet count increased from 16,000/mm3 at baseline to a median peak of 105,000/mm3 while on fostamatinib.
Adverse events considered probably related to fostamatinib were diarrhea (n=6), an increase in systolic blood pressure of more than 10 mm Hg (n=5), nausea (n=4), headache (n=4), weight gain of more than 5 kg (n=3), vomiting (n=3), abdominal pain (n=3), constipation (n=2), and alanine aminotransferase levels greater than 2 times the upper limit of normal (n=2).
Three patients stopped treatment due to adverse events. One patient developed a urinary tract infection and deep vein thrombosis (both considered unrelated to treatment).
The second patient withdrew consent due to gastrointestinal toxicity. And the last patient withdrew consent due to preexisting elevated transaminase levels that worsened on fostamatinib and prevented increases in the dose.
About orphan designation
The FDA grants orphan designation to drugs that are intended to treat diseases or conditions affecting fewer than 200,000 patients in the US.
Orphan designation provides the sponsor of a drug with various development incentives, including opportunities to apply for research-related tax credits and
grant funding, assistance in designing clinical trials, and 7 years of US marketing exclusivity if the drug is approved.
