Topline Data from Phase 2 of Fostamatinib in Nephropathy Announced

Topline data from Rigel Pharmaceuticals’ proof-of-concept Phase 2 study of fostamatinib in patients with IgA nephropathy (IgAN), or Berger’s disease, were announced today.

Safety and efficacy, as measured by change in proteinuria and renal function, were evaluated throughout, and the mean change in proteinuria (sPCR) was -177, -577, and -158 mg/g for the placebo, 100 mg bid and 150 mg bid dose groups, respectively; not statistically significant.

The study, intended to evaluate mean change in proteinuria comparing fostamatinib dose groups to placebo controls in all enrolled participants, was conducted at multiple centers throughout the U.S., Asia and Europe, and randomized patients into one of 3 groups: placebo, fostamatinib at 100 mg bid, or fostamatinib at 150 mg bid for 24 weeks.

Despite the primary endpoint not being met, the initial data did show a greater reduction in proteinuria in fostamatinib-treated patients in a pre-specified subgroup analysis of patients with greater than 1 gram/day of proteinuria at baseline. Those patients have an increased risk of disease progression and represent an unmet medical need.

"We find the subgroup analysis encouraging because patients and physicians have been challenged to manage this serious disease that has no approved treatment options," stated Raul Rodriguez, president and CEO of Rigel in a press release. "This study has provided valuable information on the potential benefit of fostamatinib in IgA nephropathy patients with significant need, those with greater than 1 gram/day of proteinuria. We will continue to evaluate the data to determine the best path forward in this indication."

In the pre-specified subgroup analysis, it was demonstrated that patients with a baseline proteinuria greater than 1 gram/day (sPCR>1000mg/g) who received fostamatinib had a dose-dependent trend towards a greater reduction in proteinuria from baseline than the placebo group at 24 weeks (Table 1).

Treatment (bid)

Median Baseline sPCR (mg/g)

Median Change from Baseline in sPCR at Week 24

Median % Change from Baseline in sPCR at Week 24

# of Patients at Week 24

Placebo

1,890

-177 mg/g

-14%

14

Fostamatinib 100 mg

2,232

-720 mg/g

-27%

16

Fostamatinib 150 mg

2,249

-803 mg/g

-36%

15

Table 1.

In patients with a baseline proteinuria greater than 2 grams, fostamatinib treatment exhibited a similar trend toward a greater reduction in proteinuria as compared to placebo.

Overall, the drug was well tolerated with most adverse events (AEs) being mild-to-moderate in severity. The most common AEs were diarrhea, nausea, headache, hypertension, and vomiting. There were no new safety signals compared to historical data across all indications.

"There are no specific therapies or treatment algorithms for the thousands of patients that suffer from this disease. So, it is important to identify a possible treatment for IgA nephropathy to reduce the risk for serious complications of progressing kidney disease, which can culminate in the need for dialysis and kidney transplantation in the worst cases," stated Professor Frederick Tam, MBBChir PhD FRCP, the Ken and Mary Minton Chair of Renal Medicine, Department of Medicine at Imperial College London, U.K. “In this Phase 2 study, the data showed a non-statistically significant trend for fostamatinib to reduce proteinuria within six months in patients with more advanced disease, which is important because there is a higher risk of kidney function loss when proteinuria increases and persists at high levels."

Next steps for Rigel include seeking out a pharmaceutical partner for the collaboration of future clinical studies of fostamatinib in IgAN.

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