On December 16, 2020, the US Food and Drug Administration approved margetuximab-cmkb (MARGENZA), in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. MARGENZA is a chimeric IgG1 monoclonal antibody that binds to HER2. The antibody’s modified Fc region increases binding to the activating Fc receptor CD16A and decreases binding to the inhibitory Fc receptor CD32B,  which leads to greater in vitro antibody-dependent cell-mediated cytotoxicity and natural killer cell activation.

FDA’s approval was based on safety and efficacy results from the pivotal Phase 3 SOPHIA trial, which showed a statistically significant 24% reduction in the risk of disease progression or death with MARGENZA plus chemotherapy compared with trastuzumab plus chemotherapy (hazard ratio [HR]=0.76; 95% CI, 0.59-0.98; P=0.033; median PFS 5.8 vs 4.9 months). The objective response rate  for MARGENZA plus chemotherapy was 22% vs 16% for trastuzumab plus chemotherapy.

MARGENZA is the 11th antibody therapeutic to be granted a first approval in the US or EU during 2020.

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

On October 14, 2020, FDA approved the triple antibody cocktail of atoltivimab, maftivimab, and odesivimab-ebgn (Inmazeb) for the treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients. Atoltivimab, maftivimab, and odesivimab are IgG1 antibodies that bind glycoprotein on the surface of Ebola virus, thereby blocking attachment and entry of the virus into cells. FDA granted the atoltivimab, maftivimab, and odesivimab cocktail Breakthrough Therapy and Orphan Drug designations for the approved indication. Inmazeb was developed by Regeneron.

The effects of Inmazeb were evaluated in adult and pediatric patients with confirmed infections that occurred during an Ebola virus outbreak in the Democratic Republic of the Congo in 2018 and 2019. In the Pamoja Tulinde Maisha (PALM) study (NCT03719586), a 4-arm trial evaluating investigational therapies for Ebola virus infection initiated in November 2018, 154 patients received Inmazeb  as a single IV infusion of 50 mg of each monoclonal antibody. The primary efficacy endpoint was 28-day mortality. At this timepoint, 33% of those who received Inmazeb had died vs 51% of those who received a control. Inmazeb was also made available in an expanded access program, which included an additional 228 patients who received Inmazeb. The PALM study was sponsored by the US National Institute of Allergy and Infectious Diseases, with collaborators from Institut National de Recherche Biomédicale (Democratic Republic of Congo); the Alliance for International Medical Action (Senegal); International Medical Corps, Los Angeles (US); Epicentre, Médecins sans Frontières, (France); and the World Health Organization (Switzerland).

Inmazeb is the 9th antibody therapeutic to be granted a first approval in the US or EU in 2020.

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

On July 31, 2020, the FDA approved Monjuvi® (tafasitamab-cxix) in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant. FDA had granted Monjuvi® an orphan drug designation for this indication, as well as Fast Track and Breakthrough Therapy designations, and the biologics license application was given a Priority Review. Monjuvi® was approved under FDA’s accelerated approval regulations, which require that further adequate and well-controlled studies/clinical trials be done to verify and describe clinical benefit. A marketing application for tafasitamab is undergoing evaluation by the European Medicines Agency.

Tafasitamab-cxix is a humanized cytolytic CD19-targeting monoclonal antibody that contains a IgG1/2 hybrid Fc-domain with 2 amino acid substitutions to modify the Fc-mediated functions of the antibody. Upon binding to CD19, tafasitamab-cxix mediates B-cell lysis through apoptosis and immune effector mechanisms, including antibody-dependent cell-mediated cytotoxicity and antibody-dependent cellular phagocytosis.

FDA’s approval was based on the efficacy of Monjuvi® in combination with lenalidomide followed by Monjuvi® as monotherapy demonstrated in L-MIND (NCT02399085), an open label, multicenter single arm trial. Results from the study showed an overall response rate of 55% (primary endpoint), including a complete response rate of 37% and a partial response rate of 18%. The median duration of response was 21.7 months. The approval was granted to MorphoSys US Inc. MorphoSys and Incyte will co-commercialize the product in the United States. Incyte has exclusive commercialization rights outside the United States.

Antibodies to watch

Tafasitamab-cxix is the 6th antibody therapeutic to be granted a first approval in the US in 2020. Marketing applications for a substantial number of investigational antibody therapeutics are currently undergoing either FDA or EMA review, including:

• Ansuvimab, a human IgG1 targeting Ebola virus glycoprotein for Ebola virus infection
• Inolimomab, a mouse IgG1 targeting CD25 for host vs. graft disease
• Bimekizumab, a humanized IgG1 targeting IL-17A, F for psoriasis
• Omburtamab, a murine IgG1 targeting B7-H3 for CNS/leptomeningeal metastases from neuroblastoma
• Tralokinumab, a human IgG4 targeting IL-13 for atopic dermatitis
• Evinacumab, a human IgG4 targeting angiopoietin-like 3 for homozygous familial hypercholesterolemia
• Sutimlimab, a humanized IgG4 targeting C1s for cold agglutinin disease
• Aducanumab, a human IgG1 targeting amyloid beta for Alzheimer’s disease
• Teplizumab, a humanized IgG1 targeting CD3 for Type 1 diabetes
• Dostarlimab, a humanized IgG4 targeting PD-1 for endometrial cancer
• Tanezumab, a humanized IgG2 targeting nerve growth factor for osteoarthritis pain
• Margetuximab, a chimeric IgG1 targeting HER2 for HER2+ breast cancer
• Naxitamab, a humanized IgG1 targeting GD2 for high-risk neuroblastoma and refractory osteomedullary disease
• Belantamab mafodotin, a humanized IgG1 antibody-drug conjugate targeting BCMA for multiple myeloma
• Oportuzumab monatox, a humanized scFv immunotoxin targeting EpCAM for bladder cancer
• REGNEB3 (odesivimab, maftivimab, atoltivimab), a mixture of 3 human IgG1 targeting Ebola virus for Ebola virus infection
• Narsoplimab, a human IgG4 targeting MASP-2 for hematopoietic stem cell transplant-associated thrombotic microangiopathies
• Satralizumab, a humanized IgG2 targeting IL-6R  for neuromyelitis optica and neuromyelitis optica spectrum disorders

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format. Information about other antibody therapeutics that may enter regulatory review in 2020 can be found in ‘Antibodies to watch in 2020’.

Like this post but not a member? Please join!