InnoCare Pharma announced that the Health Sciences Authority (HSA) of Singapore has approved HIBRUKA (orelabrutinib) for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (R/R MZL). This marks the second indication approval for the BTK inhibitor in Singapore, expanding treatment options for patients with this indolent B-cell non-Hodgkin's lymphoma.
Clinical Efficacy Demonstrates Strong Response Rates
The approval is supported by data from a multicenter, open-label phase 2 study (NCT03797456) that enrolled 90 evaluable patients with MZL. At a median follow-up of 24.3 months, the study demonstrated an independent review committee-assessed objective response rate (ORR) of 58.9% (95% CI, 48.0%-69.2%). The response comprised a complete response rate of 11.1% and a partial response rate of 47.8%.
The median time to response was 5.8 months (95% CI, 3.8-14.2), while the median duration of response reached 34.3 months (95% CI, not reached). Progression-free survival data showed promise, with the median not yet reached. The 12-month and 24-month PFS rates were 82.8% (95% CI, 72.6%-89.5%) and 75.8% (95% CI, 63.9%-84.2%), respectively.
Overall survival outcomes were encouraging, with the median not reached. The OS rates were 91.0% (95% CI, 82.8%-95.4%) at 12 months and 86.8% (95% CI, 77.2%-92.5%) at 24 months.
Patient Population and Treatment Protocol
The phase 2 trial enrolled patients aged 18 to 75 years with MZL who had received at least one but no more than four prior therapies, including treatment with an anti-CD20 monoclonal antibody. In the 90 evaluable patients, the median age was 62.0 years, with 41.1% aged 65 years or older and 54.4% being male.
Regarding disease subtypes, 46.7% of patients had mucosa-associated lymphoid tissue, 35.6% had nodal MZL, and 5.6% had splenic MZL. Most patients presented with stage IV disease (75.6%), and 54.4% had received only one prior line of therapy.
Participants received orelabrutinib at a once-daily dose of 150 mg in 28-day cycles, continuing treatment until progressive disease, unacceptable toxicity, withdrawn consent, or death.
Safety Profile Shows Manageable Toxicities
Among 111 safety-evaluable patients, 98.2% experienced an adverse event, with 90.1% experiencing at least one treatment-related adverse event (TRAE). The most common all-grade TRAEs included anemia (27.9%), decreased neutrophil count (23.4%), decreased white blood cell count (18.0%), decreased platelet count (17.1%), blood present in urine (16.2%), rash (14.4%), and upper respiratory infection (10.8%).
Grade 3 or higher TRAEs reported in at least 2% of patients included decreased neutrophil count (8.1%), pneumonia (6.3%), anemia (4.5%), and decreased white blood cell count (3.6%). Pneumonia was the most frequently reported serious TRAE, occurring in 5.4% of patients. Seven patients discontinued treatment due to TRAEs.
Addressing Unmet Medical Need
"We are excited to obtain a second indication approval in Singapore. As a highly selective BTK inhibitor, orelabrutinib has demonstrated good efficacy and safety in the treatment of R/R MZL," said Dr. Jasmine Cui, Co-founder, Chairwoman and CEO of InnoCare. "The approval in Singapore will offer a new treatment option to local lymphoma patients."
Marginal zone lymphoma is an indolent B-cell non-Hodgkin's lymphoma that primarily affects middle-aged and elderly patients, with annual incidence rising globally. After first-line treatment, patients with relapsed or refractory MZL face limited effective treatment options, highlighting the clinical significance of this approval.
Broader Development Program
Orelabrutinib is a novel BTK inhibitor developed by InnoCare with high target selectivity designed to minimize off-target effects, thereby improving both safety and efficacy. The drug has received breakthrough therapy designation from the FDA for relapsed or refractory mantle cell lymphoma in June 2021.
In April 2025, orelabrutinib received approval in China for first-line treatment of patients with chronic lymphocytic leukemia and small lymphocytic lymphoma. The drug has also been approved for three other indications in China, including relapsed and refractory CLL/SLL, relapsed/refractory mantle cell lymphoma, and relapsed/refractory marginal zone lymphoma, all covered under China's National Reimbursement Drug List.
InnoCare is advancing global clinical trials for orelabrutinib in autoimmune diseases, expanding the potential therapeutic applications of this selective BTK inhibitor beyond oncology indications.
