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FDA Approves Genentech’s Columvi, the First and Only Bispecific Antibody With a Fixed-Duration Treatment for People With Relapsed or Refractory Diffuse Large B-cell Lymphoma

BusinessWire

– Pivotal study showed durable responses, with a 56% overall response rate, a 43% complete response (remission) rate, and a median duration of response of 1.5 years (18.4 months) –

– Given over a fixed period of time, Columvi provides patients with a treatment end date and potential time off treatment –

– Columvi is part of Genentech’s industry-leading portfolio of T-cell engaging bispecific antibodies in non-Hodgkin’s lymphoma, which also includes the recently approved Lunsumio to treat follicular lymphoma –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has approved Columvi® (glofitamab-gxbm) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate and durability of response in the Phase I/II NP30179 study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Columvi will be available in the United States in the coming weeks.

“People with diffuse large B-cell lymphoma who have gone through multiple lines of therapy have a poor prognosis and desperately need additional treatment options,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “As an off-the-shelf, fixed-duration treatment providing durable response rates, we believe Columvi could change the way this aggressive lymphoma is treated, reinforcing our dedication to bringing innovative treatment options to people with critical unmet needs.”

DLBCL is an aggressive, hard-to-treat disease and is the most common form of non-Hodgkin’s lymphoma in the United States. While many people with DLBCL are responsive to treatment, the majority of those who relapse or are refractory to subsequent treatments have poor outcomes.

“Patients with relapsed or refractory diffuse large B-cell lymphoma may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” said Krish Patel, M.D., Director of the Lymphoma Program at the Swedish Cancer Institute in Seattle and investigator of the Columvi Phase I/II NP30179 study. “Experience from clinical trials demonstrates that Columvi can provide patients with relapsed or refractory diffuse large B-cell lymphoma a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”

The FDA accelerated approval is based on positive results from the Phase I/II NP30179 study of Columvi given as a fixed course for 8.5 months in 132 patients with DLBCL who had relapsed or were refractory to prior therapies, including about one-third (30%) who had received prior CAR T-cell therapy. Additionally, 83% were refractory to their most recent therapy. Results showed patients treated with fixed-duration Columvi achieved durable remission, with 56% of patients achieving an overall response (OR; 74/132 [95% confidence interval (CI): 47-65]) and 43% of patients achieving a complete response (CR; 57/132 [95% CI: 35-52]). Over two-thirds of those who responded continued to respond for at least nine months (68.5% [95% CI: 56.7-80.3]). The OR rate is the combination of CR rate (a disappearance of all signs and symptoms of cancer) and partial response rate (a decrease in the amount of cancer in the body). The median duration of response was 1.5 years (18.4 months [95% CI: 11.4-not estimable]). Data from the NP30179 study were recently published in the New England Journal of Medicine.

Among 145 patients who received Columvi in the study, the most common adverse events (AEs) were cytokine release syndrome (CRS; 70%), which may be serious or life-threatening, musculoskeletal pain (21%), fatigue (20%) and rash (20%). CRS was generally low grade (52% experienced Grade 1, and 14% experienced Grade 2).

Columvi is the first and only CD20xCD3 T-cell engaging bispecific antibody for the treatment of R/R DLBCL that is given for a defined period of time. Unlike treat-to-progression approaches where treatment is given indefinitely until the cancer progresses or the therapy cannot be tolerated, Columvi is administered in 13 intravenous infusions over a maximum of 12 cycles (including step-up dosing) or until disease progression or the treatment cannot be tolerated, whichever occurs first. After Cycle 1, Columvi is administered once every three weeks. Designed to be completed in approximately 8.5 months, Columvi offers people with R/R DLBCL a target end date for their course of treatment and the possibility of a treatment-free period. Additionally, Columvi is a chemotherapy-free treatment option that is off-the-shelf and ready for infusion. Patients are pretreated with a single dose of obinutuzumab seven days prior to starting Columvi. Patients are also given a corticosteroid, an antipyretic (fever-reducing medicine) and an antihistamine as premedications to reduce the risk of CRS.

Columvi is part of Genentech’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development program. This includes the Phase III STARGLO study evaluating Columvi in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in patients with DLBCL who have been treated with one or more previous therapies and are ineligible for autologous stem cell transplant. Genentech’s hematology bispecific antibody portfolio also includes Lunsumio® (mosunetuzumab-axgb), which was granted accelerated approval by the FDA in December 2022 for the treatment of adult patients with R/R follicular lymphoma after two or more lines of systemic therapy. Genentech is exploring the potential of both Columvi and Lunsumio as monotherapies and in combination with other therapies, including Polivy® (polatuzumab vedotin-piiq), in earlier lines of treatment with the goal of providing patients with long-lasting outcomes. This robust development program includes two Phase III studies: CELESTIMO, investigating Lunsumio plus lenalidomide in second line plus (2L+) FL, and SUNMO, investigating Lunsumio plus Polivy in 2L+ DLBCL. Columvi received its first worldwide approval in Canada, and the European Medicines Agency’s Committee for Medicinal Products for Human Use recently granted a positive opinion recommending its approval.

Genentech is committed to helping people access the medicines they are prescribed and will be offering comprehensive services for people prescribed Columvi to help minimize barriers to access and reimbursement. For people who qualify, Genentech plans to offer patient assistance programs through Genentech Access Solutions. More information is also available at 866-4ACCESS/866-422-2377 or http://www.Genentech-Access.com.

About the NP30179 Study

The NP30179 study [NCT03075696] is a Phase I/II, multicenter, open-label, dose-escalation and expansion study evaluating the safety, efficacy and pharmacokinetics of Columvi® (glofitamab-gxbm) in people with relapsed or refractory diffuse large B-cell lymphoma. Outcome measures include complete response rate by an independent review committee (primary endpoint), overall response rate, duration of response, progression-free survival, safety and tolerability (secondary endpoints).

About Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast-growing) blood cancer and is the most common form of non-Hodgkin’s lymphoma (NHL) in the U.S. While many people with DLBCL are responsive to treatment, the majority of those who relapse or are refractory to subsequent treatments have poor outcomes. DLBCL not otherwise specified is the most common category of large B-cell lymphoma (LBCL) and accounts for about 80% or more of cases. It applies to cases that do not fall into any specific disease subgroups of LBCL.

About Large B-Cell Lymphoma Arising from Follicular Lymphoma

Follicular lymphoma (FL) is the most common slow-growing (indolent) form of non-Hodgkin’s lymphoma (NHL), accounting for about one in five cases. It typically responds well to treatment but is often characterized by periods of remission and relapse. The disease typically becomes harder to treat each time a patient relapses, and early progression can be associated with poor long-term prognosis. As part of the natural history of FL, it can transform to more aggressive malignancies, including large B-cell lymphoma (LBCL), one of the most aggressive (fast-growing) blood cancers.

About Columvi® (glofitamab-gxbm)

Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed with a novel 2:1 structural format. Columvi targets both T cells, a type of immune cell, and B cells, which are cancerous in DLBCL. Columvi is engineered to have one region that binds to CD3, a protein on T cells, and two regions that bind to CD20, a protein on B cells, which can be healthy or cancerous. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell that result in the death of B cells. A robust clinical development program for Columvi is ongoing, investigating the molecule as a monotherapy and in combination with other medicines for the treatment of people with B-cell non-Hodgkin’s lymphomas, including diffuse large B-cell lymphoma and other blood cancers.

Columvi U.S. Indication

Columvi (glofitamab-gxbm) is a prescription medicine to treat adults with certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) that has come back (relapsed) or that did not respond to previous treatment (refractory), and who have received 2 or more prior treatments for their cancer.

It is not known if Columvi is safe and effective in children.

The conditional approval of Columvi is based on response rate and durability of response. There are ongoing studies to establish how well the drug works.

What is the most important information I should know about Columvi?

Columvi can cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Columvi, and can also be serious and lead to death.

Call your healthcare provider or get emergency medical help right away if you develop any signs or symptoms of CRS, including:

Due to the risk of CRS, you will receive Columvi on a “step-up dosing schedule”.

Your healthcare provider will monitor you for CRS during treatment with Columvi and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Columvi if you have severe side effects.

Carry the Columvi Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Columvi Patient Wallet Card lists the signs and symptoms of CRS you should get emergency medical help for right away.

What are the possible side effects of Columvi?

Columvi may cause serious side effects, including:

The most common side effects of Columvi include: CRS, muscle and bone pain, rash, and tiredness.

The most common severe abnormal lab test results with Columvi include: decreased white blood cells, decreased phosphate (an electrolyte), increased uric acid levels, and decreased fibrinogen (a protein that helps with blood clotting).

Your healthcare provider may temporarily stop or completely stop treatment with Columvi if you develop certain side effects.

Before receiving Columvi, tell your healthcare provider about all of your medical conditions, including if you:

Females who are able to become pregnant:

Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while receiving Columvi?

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, shaking (tremors), sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of neurologic problems.

These are not all the possible side effects of Columvi. Talk to your health care provider for more information about the benefits and risks of Columvi.

You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see Important Safety Information, including Serious Side Effects, as well as the Columvi full Prescribing Information and Medication Guide or visit https://www.Columvi.com.

About Lunsumio® (mosunetuzumab-axgb)

Lunsumio is a first-in-class CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B cells and CD3 on the surface of T cells. This dual targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development program for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin’s lymphomas, including follicular lymphoma and diffuse large B-cell lymphoma, and other blood cancers.

Lunsumio U.S. Indication

Lunsumio (mosunetuzumab-axgb) is a prescription medicine used to treat adults with follicular lymphoma whose cancer has come back or did not respond to previous treatment, and who have already received two or more treatments for their cancer.

It is not known if Lunsumio is safe and effective in children.

The conditional approval of Lunsumio is based on response rate. There are ongoing studies to establish how well the drug works.

What is the most important information I should know about Lunsumio?

Lunsumio may cause Cytokine Release Syndrome (CRS), a serious side effect that is common during treatment with Lunsumio and can also be severe or life-threatening.

Get medical help right away if you develop any signs or symptoms of CRS at any time, including:

Due to the risk of CRS, you will receive Lunsumio on a “step-up dosing schedule.”

Your healthcare provider will check you for CRS during treatment with Lunsumio and may treat you in a hospital if you develop signs and symptoms of CRS. Your healthcare provider may temporarily stop or completely stop your treatment with Lunsumio, if you have severe side effects.

What are the possible side effects of Lunsumio?

Lunsumio may cause serious side effects, including:

Your healthcare provider may temporarily stop or permanently stop treatment with Lunsumio if you develop severe side effects.

The most common side effects of Lunsumio include: tiredness, rash, fever, and headache.

The most common severe abnormal lab test results with Lunsumio include: decreased phosphate, increased glucose, and increased uric acid levels.

Before receiving Lunsumio, tell your healthcare provider about all of your medical conditions, including if you:

Females who are able to become pregnant:

Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

What should I avoid while receiving Lunsumio?

Do not drive, operate heavy machinery, or do other dangerous activities if you develop dizziness, confusion, tremors, sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of CRS or neurologic problems.

These are not all the possible side effects of Lunsumio. Talk to your health care provider for more information about the benefits and risks of Lunsumio.

You may report side effects to the FDA at (800) FDA-1088 or http://www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see Important Safety Information, including Serious Side Effects, as well as the Lunsumio full Prescribing Information and Medication Guide or visit https://www.Lunsumio.com.

About Polivy® (polatuzumab vedotin-piiq)

Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells.

Contacts

Media Contact:

Lindsey Mathias, (650) 467-6800

Advocacy Contact:

Cem Mangir, (202) 251-4037

Investor Contacts:

Loren Kalm, (650) 225-3217

Bruno Eschli, 011 41 61 687 5284

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