Rigel Pharma—just days away from hearing from the FDA on its first marketing application for lead drug fostamatinib—has reported disappointing phase 2 data in a follow-up indication.
The California biotech said this morning that oral spleen tyrosine kinase inhibitor fostamatinib was unable to hit its primary endpoint in a proof-of-concept study involving patients with IgA nephropathy (IgAN), an orphan autoimmune disease of the kidneys. It did however suggest that the drug had shown some evidence of efficacy in a subgroup of more seriously ill IgAN patients.
It’s nevertheless a setback for the company’s longer-term ambitions for fostamatinib, which is due for a verdict from the FDA on lead indication immune thrombocytopenic purpura (ITP) by April 17.
Shares in Rigel slid after hours and were down more than 11% at the time of writing.
Fostamatinib is also in phase 2 trials for warm antibody autoimmune hemolytic anemia, but IgAN is considered to be the largest of all three target indications—all of which are fairly rare—and affects an estimated 82,500 to 165,000 people in the U.S. alone.
It’s also not the first time that the drug hasn’t quite hit the mark in clinical trials. It previously failed as a rheumatoid arthritis candidate and posted less-than-stellar results in ITP, although investors have been encouraged by the FDA’s decision not to convene an advisory committee meeting to review its application.
In the IgAN study, fostamatinib was unable to achieve a statistically significant reduction in the level of protein in the urine—a marker for kidney damage—compared to placebo. The biotech is taking some comfort from a prespecific subgroup of patients with proteinuria levels of more than 1 gram per day, who are at greater risk of rapid disease progression.
In that group, fostamatinib did show a trend to improvement over placebo but once again wasn’t able to hit the threshold for statistical significance. Additional data looking at the effect of fostamatinib on cell histology will be reported later this year.
Rigel CEO Raul Rodriguez said in a release that the subgroup analysis is encouraging “because patients and physicians have been challenged to manage this serious disease that has no approved treatment options" and current guidance is for trials to enroll patients with greater than 1 gram/day proteinuria.
That was the objective in this trial, although the threshold was expanded to include patents who had that level of proteinuria in the past but had a level greater than 500 mg to facilitate enrollment.
Rigel will “continue to evaluate the data to determine the best path forward in this indication," he added in the release. On a conference call, he also said the company remained “very optimistic” about the outcome of the FDA’s review of fostamatinib for ITP.
Some of the other players developing drugs for the treatment of IgAN include Mallinckrodt, Merck KGaA, Novartis, Shire, Omeros and Anthera, according to P&S Market Research, which says that there are currently 24 drug candidates in different stages of development for the disease.