Rilzabrutinib awarded orphan drug status in Japan for IgG4-RD
Designation now in 3 countries, aims to speed rare disease drug development
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Regulatory authorities in Japan have granted orphan drug designation to rilzabrutinib, an oral therapy candidate for immunoglobulin G4-related disease (IgG4-RD) that’s now in late-stage clinical testing globally.
In Japan, orphan drug designation is awarded to experimental medicines that aim to treat diseases affecting fewer than 50,000 people in the country. The goal is to offer extra incentives and support for companies that are investing in treatments for rare diseases.
Regulators in the U.S. and the European Union, which have similar classifications for rare diseases — conditions affecting less than 200,000 people in the U.S., or fewer than 5 of every 10,000 people in the EU — have also named rilzabrutinib an orphan drug for IgG4-RD.
“There is still unmet medical need and limited treatment options in Japan for IgG4-RD, a rare, progressive, immune-mediated chronic condition in which the immune system attacks various tissues and organs leading to serious damage,” Sanofi, the company developing rilzabrutinib, stated in a company press release announcing the new designation.
A Phase 3 clinical trial called RILIEF (NCT07190196) is testing rilzabrutinib against a placebo in adults with active IgG4-RD. An estimated 124 participants are being recruited at dozens of sites worldwide, including five in Japan.
A rare inflammatory disorder, IgG4-RD is marked by abnormal clumps of immune cells that can result in tumor-like masses and swelling in virtually any part of the body. The condition can lead to a wide range of symptoms, which may include unexplained weight loss and swollen lymph nodes.
Initial treatment usually involves anti-inflammatory therapies called glucocorticoids, but because their long-term use can cause serious side effects, patients usually taper off these meds once the disease is controlled. However, patients can then experience disease flare-ups with new or worsening symptoms.
Rilzabrutinib designed to ease symptoms of IgG4-RD
Rilzabrutinib is designed to suppress Bruton’s tyrosine kinase (BTK), a protein that plays key roles in the inflammatory activation of several types of immune cells, including those involved in IgG4-RD. Given this, the therapy is expected to reduce the immune responses that drive the disease, easing its symptoms.
The oral therapy is already approved in the U.S., the EU, and the United Arab Emirates for immune thrombocytopenia, a rare autoimmune bleeding disorder. It’s sold for that indication under the name Wayrilz.
Rilzabrutinib’s new designation in Japan was granted following positive data from a Phase 2 clinical trial (NCT04520451) that tested rilzabrutinib plus glucocorticoids against glucocorticoids alone in about two dozen adults with IgG4-RD. The study was open-label, meaning patients knew whether or not they received the experimental treatment.
The results showed that, after about a year, 70% of rilzabrutinib-treated patients were free from flares without the need for glucocorticoids or other immunosuppressive treatments. Clinically meaningful reductions in disease activity were seen as early as three months, and sustained through one year.
Safety findings from the small trial were in line with rilzabrutinib’s known safety profile, without any new concerns raised, according to Sanofi. Commonly reported adverse events included diarrhea, nausea, dizziness, and dry mouth. Some patients also developed COVID-19.
Therapy’s safety, effectiveness now being tested in Phase 3 trial
The ongoing Phase 3 RILIEF trial is further evaluating the safety and efficacy of rilzabrutinib in adults with IgG4-RD. Unlike the Phase 2 study, RILIEF is placebo-controlled: Participants are randomly assigned to receive either rilzabrutinib or a placebo in addition to glucocorticoids for about one year. This trial is also double-blind, meaning that neither participants nor researchers know who gets the experimental therapy and who’s on the placebo.
The main goal is to determine whether rilzabrutinib delays time to first disease flare. Secondary goals include assessing the proportions of patients without flares and off glucocorticoids and other medications, the annualized rate of flares, changes in validated measures of disease activity, cumulative glucocorticoid doses, and the therapy’s safety.
