Roche Impresses with its Bispecific Antibody Portfolio for Blood Cancer Treatments

In the recently concluded ASH meeting, Roche presented new updates of its bispecific antibodies developed for blood cancer treatments. The company released encouraging new data from four clinical trials in a variety of blood cancer patients, including Non-Hodgkin Lymphoma (NHL) and myeloma.

Blood cancer is one of the most common forms of cancer, accounting for approximately 10% of all cancer deaths in the US. Currently, as many as 1.2 million people are living with the disease, with 178,000 estimated to be diagnosed in 2020 alone. Traditional treatments include chemotherapy, blood transfusion, among others. However, recent advances in the field of immunotherapy, such as Chimeric Antigen Receptor T-cell therapy (CAR-T) and monoclonal antibody therapy, have proved to be valuable.

CrossMab Technology

Roche’s patented CrossMab technology is a platform used to develop antibodies that can bind to multiple targets, thereby targeting multiple types of cells simultaneously. This reduces the potential side effects and number of injections while increasing the efficacy of the antibodies. Further, this makes use of the host antibodies, thereby reducing host response against the drugs. Using this technology, Roche has developed multiple bio-specific antibodies to treat blood cancer using this technology.

Mosunetuzumab and glofitamab are two antibodies that can activate T-cells to induce an immune response against cancer cells. By targeting CD20 on the malignant B-cells and CD3 on the surface of T-cells, the antibodies bring the T-cells close to the cancer cells and then release cytotoxic factors to kill them. These drugs are currently under investigation for the treatment of B-cell non-Hodgkin and other blood cancers.

Cevostamab is another dual target antibody that engages the FcRH5 receptor on myeloma cells and CD3 on T-cells. The FcRH5 receptor is expressed in almost all myeloma cells, making it a unique target. This antibody helps redirect T cells to the myeloma cells and then eliminate them by releasing cytotoxic factors. The drug is also structurally similar to natural host antibodies.

Encouraging Trial Data

Mosunetuzumab and glofitamab have been studied in multiple clinical trials either as a monotherapy or in combination with other drugs in patients with NHL. Approximately 52% of patients with follicular lymphoma treated with Mosunetuzumab achieved a complete response (CR) in the Phase I clinical trial (GO29781). Further, 54% of the patients treated with glofitamab achieved a complete response in a separate clinical trial (NP30179). Mosunetuzumab also showed encouraging results in a Phase I trial (GO40554) with elderly unfit patients with B-cell lymphoma, where 45% of the patients achieved CR. The CR was much higher, at 79%, in patients treated with Mosunetuzumab in combination with chemotherapy (GO40515).

The first clinical trial with Roche’s FcRH5xCD3 bispecific antibody also showed promising results in myeloma patients. Patients receiving the drug demonstrated an overall response rate of 53%. These responses were seen in high-risk patients who have been treated heavily before. For all 3 drugs, the major adverse event noted was cytokine release syndrome.

Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development, said, “The data suggest that our novel bispecific antibodies have potential across multiple types of blood cancers and supports the broad exploration of these new immunotherapy approaches across different patient populations and treatment lines. Lymphoma and multiple myeloma are challenging cancers to treat, especially when patients present with aggressive subtypes or experience multiple relapses, but ‘off-the-shelf’ therapies like these could provide new options that may potentially enable patients to be treated quickly.”

Competition

CAR-T cell therapy had been at the forefront of different blood cancer treatments since its approval in 2017. Gilead’s Yescarta and Novartis’s Kymriah are both approved CAR-T cell therapy for various types of blood cancers. Further, BMS is also in the process of having their CAR-T cell drug liso-cel approved. However, these kinds of therapies are expensive and come with a hefty price tag. Another major drawback is that these therapies are not off the shelf. Moreover, Roche has previously demonstrated that their bispecific antibodies can be useful in patients where CAR-T therapy has not been successful. Further, Roche’s competitor, Regeneron, has shown that their CD20xCD3 bispecific antibody, REGN1979, can also trigger a response in NHL patients treated with CAR-T cells. It will be interesting to see if Roche’s patented CrossMab technology will give them an edge over their competitors in the coming years.

By T. Chakraborty, Ph.D.

Related Article: Novartis’ Chronic Myeloid Leukemia Drug Demonstrates Superior Results to Pfizer’s

References

1. https://www.roche.com/media/releases/med-cor-2020-12-08.htm
2. https://www.lls.org/facts-and-statistics/facts-and-statistics-overview/facts-and-statistics
3. https://www.roche.com/research_and_development/what_we_are_working_on/research_technologies/bispecific-antibodies.htm

Author

Tulip Chakraborty