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FDA Grants Priority Review to Genentech’s Bispecific Antibody Glofitamab for People With Relapsed or Refractory Large B-Cell Lymphoma

Update: Columvi (glofitamab-gxbm) Now FDA Approved - June 15, 2023

South San Francisco, CA -- January 5, 2023 -- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted the company’s Biologics License Application (BLA) and granted Priority Review for glofitamab, an investigational CD20xCD3 T-cell engaging bispecific antibody, for the treatment of adult patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) after two or more lines of systemic therapy. LBCL is an aggressive (fast-growing) type of non-Hodgkin’s lymphoma (NHL) and is one of the most prevalent types of blood cancer among adults in the U.S. The FDA is expected to make a decision on approval of this novel cancer immunotherapy by July 1, 2023. If approved, glofitamab would be the first fixed-duration, off-the-shelf CD20xCD3 T-cell engaging bispecific antibody available to treat people with an aggressive lymphoma who have previously received multiple courses of treatment.

“Unfortunately, people with relapsed or refractory large B-cell lymphoma have a poor prognosis and desperately need additional therapies that are immediately available at the time of relapse,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “Even for patients whose cancer is rapidly progressing, glofitamab given for a fixed duration has shown impressive efficacy and long-term durability, with patients continuing to experience a complete remission after treatment has concluded.”

The BLA is based on positive data from the pivotal Phase I/II NP30179 study, which included patients who had previously received multiple courses of therapy, with 85.1% of patients refractory to their most recent therapy and about one-third (33.1%) having received prior CAR T-cell therapy. Results showed that 40.0% of patients (n=62/155) achieved a complete response (CR; a disappearance of all signs of cancer), and 51.6% (n=80/155) achieved an objective response (OR; the combination of CR and partial response, a decrease in the amount of cancer in their body). The median follow-up time was 13.4 months. Among those who achieved a CR, 73.1% continued to experience a response at 12 months, while the median duration of CR was not reached. The median duration of response was 18.4 months.

An earlier cut-off of data from the Phase I/II study showed that glofitamab given as a fixed-duration treatment resulted in early and durable complete remissions. In this analysis, presented at the 64th American Society of Hematology 2022 Annual Meeting and simultaneously published in the New England Journal of Medicine in December 2022, most patients who had achieved a CR at the end of treatment experienced durable responses. The median CR follow-up from the end of treatment was 11.5 months (95% confidence interval [CI]: 10.5-16.4). Twelve months after the end of treatment with glofitamab, 61% of patients (n=37/61) maintained a CR, 92.6% remained progression-free, and only one patient (n=1/44) experienced disease progression.

The most common adverse event was cytokine release syndrome (CRS), which was generally low grade (48.1% of patients had Grade 1 and 12.3% had Grade 2). Most CRS events were associated with initial administration of glofitamab (in cycle 1). The incidence of Grade 3 or higher CRS was 3.9%, with no Grade 5 events. Only one patient (n=1/155) discontinued glofitamab due to CRS.

The FDA will review the glofitamab BLA under the granted Fast Track Designation. Data from the Phase I/II NP30179 study of glofitamab were submitted for review to the European Medicines Agency, and submissions to additional health authorities worldwide are ongoing.

Glofitamab is part of Genentech’s industry-leading CD20xCD3 T-cell engaging bispecific antibody clinical program, which is the broadest and most advanced in lymphoma. Genentech’s portfolio also includes Lunsumio® (mosunetuzumab-axgb), which was granted accelerated approval by the FDA and conditional marketing authorization by the European Commission for the treatment of adults with R/R follicular lymphoma who have received at least two prior systemic therapies.

A robust clinical development program for glofitamab is ongoing, including the Phase III STARGLO trial, evaluating glofitamab in combination with gemcitabine and oxaliplatin (GemOx) versus rituximab in combination with GemOx in patients with second-line plus diffuse large B-cell lymphoma (DLBCL) who are ineligible for autologous stem cell transplant. Additional studies are ongoing to investigate the molecule as a monotherapy and in combination with other medicines for the treatment of patients with B-cell non-Hodgkin’s lymphomas, including DLBCL, mantle cell lymphoma and other blood cancers.

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 glofitamab in people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). 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 Large B-Cell Lymphoma
Large B-cell lymphoma (LBCL) is an aggressive (fast-growing) blood cancer and is one of the most prevalent blood cancers among adults. Diffuse large B-cell lymphoma (DLBCL), a subtype of LBCL, is the most common form of non-Hodgkin’s lymphoma (NHL) and accounts for almost a third of NHL diagnoses. While many patients are responsive to initial treatment, four out of 10 are not cured with the current standard of care, and the majority of patients who require subsequent lines of therapy have poor outcomes.

About Glofitamab
Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Glofitamab was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. 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. A robust clinical development program for glofitamab 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.

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 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.

About Genentech in Hematology

For more than 20 years, Genentech has been developing medicines with the goal to redefine treatment in hematology. Today, we’re investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. For more information visit http://www.gene.com/hematology.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

Source: Genentech

Posted: January 2023

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