Roche's Two Novel Class 1 Drugs—CD3/CD20 Bispecific Antibody and C5 Monoclonal Antibody—Granted Breakthrough Therapy Designation by CDE

Author: Sunshine

On July 30, the CDE official website announced that two Class 1 innovative drugs from Roche have been proposed for Breakthrough Therapy Designation by the CDE and are now open for public notice. The two new drugs are: RO7082859, a CD3/CD20 bispecific antibody, for adult patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) following two or more prior lines of systemic therapy, including diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS), high-grade B-cell lymphoma (HGBCL), DLBCL transformed from follicular lymphoma (trFL), and primary mediastinal large B-cell lymphoma (PMBCL); and RO7112689, a C5 monoclonal antibody, for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) who weigh ≥40 kg and are not currently receiving complement inhibitor therapy.

CD3/CD20 bispecific antibody RO7082859

RO7082859 (glofitamab, CD20-TCB) is a novel "2:1" bispecific antibody developed by Roche, comprising two CD20-binding Fab fragments and one CD3ε-binding Fab fragment. The activity of this "2:1" CD20-TCB is 10- to 1000-fold higher than that of conventional "1:1" bispecific antibodies.

Data from the Phase I/Ib dose-escalation NP30179 study presented by Roche at the ASH 2019 meeting showed that among patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) treated with glofitamab in combination with obinutuzumab across the 0.6 mg to 16 mg dose range, the overall response rate (ORR) was 54% (n=15/28) and the complete response (CR) rate was 46% (n=13/28). Across all treatment doses, the most common adverse event was cytokine release syndrome (CRS), with an incidence of 67.9% (n=19/28), mostly Grade 1–2. The results indicate that treatment with glofitamab in combination with obinutuzumab yields highly effective and durable complete responses with a manageable safety profile.

Data presented at the 2021 ASCO meeting demonstrated that dose escalation of glofitamab monotherapy achieved a preliminary overall response rate higher than previously reported in patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL) who had failed multiple prior lines of therapy. Cytokine release syndrome (CRS) was predominantly low-grade and manageable.

Besides glofitamab, Roche has also developed mosunetuzumab, a CD3/CD20 bispecific antibody, which is currently in global Phase III clinical trials. It received approval from the drug regulatory authority to initiate clinical trials in February 2021. Additionally, seven CD3/CD20 bispecific antibody candidates have been submitted for regulatory approval in China. Zai Lab is closely following Roche, with its candidate currently in Phase II clinical trials.

Source: PharmaCube NextPharma

C5 Monoclonal Antibody RO7112689

Paroxysmal nocturnal hemoglobinuria (PNH) is a non-malignant clonal disorder caused by PIG-A mutations. It is an acquired disease of pluripotent hematopoietic stem cells that often exacerbates during sleep. Clinically, it is primarily characterized by chronic intravascular hemolysis, hematopoietic failure, and recurrent thrombosis. The disease has been included in China's "First Catalog of Rare Diseases".

Currently, there are three FDA-approved drugs for the treatment of PNH: Alexion’s complement C5 monoclonal antibody Soliris (eculizumab), the long-acting C5 monoclonal antibody Ultomiris (ravulizumab), and Swedish Orphan Biovitrum’s C3 inhibitor pegcetacoplan. Alexion’s two drugs generated $4.285 billion in sales in 2019.

Source: NextPharma

RO7112689 (crovalimab) is a novel recycling antibody that provides prolonged C5 neutralization compared to conventional antibodies. Additionally, crovalimab can effectively inhibit the R885H mutant, whereas eculizumab demonstrates poor efficacy in patients with this mutation.

Roche is conducting a Phase I/II clinical trial (NCT03157635), a first-in-human study of the C5 monoclonal antibody crovalimab, aimed at evaluating the safety and efficacy of crovalimab in healthy volunteers and patients with PNH, as well as the related pharmacokinetics and pharmacodynamics.