approved antibodies Archives - The Antibody Society

Aduhelm (aducanumab) approved for the treatment of Alzheimer’s disease.

June 7, 2021 by Janice Reichert

On June 7, 2021, the U.S. Food and Drug Administration approved Aduhelm (aducanumab) for the treatment of Alzheimer’s disease. Developed by Biogen, aducanumab is a human IgG1 antibody that targets anti-amyloid b. Biogen licensed the worldwide rights to aducanumab from Neurimmune in 2007, and has collaborated with Eisai on the global development and commercialization of aducanumab since 2017.

The late-stage development program for Aduhelm consisted of two Phase 3 clinical trials. One study met the primary endpoint, showing reduction in clinical decline. The second trial did not meet the primary endpoint. In all studies in which it was evaluated, Aduhelm reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion. The reduction in amyloid plaque is considered a surrogate for a reduction in clinical decline. Aduhelm was approved using FDA’s accelerated approval pathway, which can be based on the drug’s effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. A post-approval trial to verify that the drug provides the expected clinical benefit is required.

Need help keeping up to date on US and EU approvals?

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.

Amivantamab granted FDA approval for non-small cell lung cancer

May 21, 2021 by Janice Reichert

On May 21, 2021, U.S. Food and Drug Administration approved Rybrevant (amivantamab-vmjw) as the first treatment for adult patients with non-small cell lung cancer (NSCLC) whose tumors have specific types of genetic mutations: epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Rybrevant received Priority Review and Breakthrough Therapy designation for this indication.

Amivantamab (JNJ-61186372; Janssen Pharmaceutical Companies of Johnson & Johnson) is a human, low-fucose IgG1-based bispecific antibody targeting EGFR and mesenchymal epithelial transition factor (MET) that was created using Genmab’s DuoBody technology. Amivantamab has been shown to function through multiple mechanisms of action in preclinical models of NSCLC with EGFR exon 20 insertion driver mutations, which cause tumor cells to be insensitive to EGFR tyrosine kinase inhibitors.

The efficacy of amivantamab was evaluated in a study of 81 patients with non-small cell lung cancer and EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. In the trial population in which all patients received the drug, the overall response rate was 40% and the median duration of response was 11.1 months, with 63% of patients having a duration of response of 6 months or more.

FDA’s review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For review of amivantamab, the FDA collaborated with the Brazilian Health Regulatory Agency and United Kingdom’s Medicines and Healthcare products Regulatory Agency.

Need help keeping up to date on US and EU approvals?

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.

Loncastuximab tesirine granted first approval by FDA for large B-cell lymphoma

April 26, 2021 by Janice Reichert

On April 23, 2021, the US Food and Drug Administration (FDA) granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics SA) for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. This marketing application was granted priority review and orphan drug designation by FDA. The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Loncastuximab tesirine (ADCT-042) is an antibody-drug conjugate composed of an anti-CD19 humanized IgG1k antibody conjugated via a linker to pyrrolobenzodiazepine-dimer toxin that induces the killing of CD19-expressing malignant B cells.

The BLA submission was supported by data from the open-label, single-arm Phase 2 LOTIS 2 study (NCT03589469), which evaluated the safety and efficacy of loncastuximab tesirine for the treatment of patients with relapsed or refractory DLBCL following ≥2 lines of prior systemic therapy. A total of 145 patients received loncastuximab tesirine as an intravenous infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg for 2 cycles, then 75 μg/kg for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria. The primary outcome measure is the overall response rate (ORR). Positive initial data from LOTIS 2 were presented during the virtual 25th Annual Congress of the European Hematology Association. The ORR was 48.3% (70/145 patients), the complete response rate was 24.1% (35/145 patients), and the median duration of response was 10.25 months. The toxicity profile was manageable and no new safety concerns were identified.

Need help keeping up to date on US and EU approvals?

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.

Triple-negative Breast Cancer Day, March 3, 2021

March 2, 2021 by Janice Reichert

On March 3rd each year, the global community affected by and working to treat triple-negative negative breast cancer (TNBC) comes together to raise awareness of this disease. Like all cancers, breast cancer is heterogenous. The triple-negative form of the disease is characterized by the absence of expression of the estrogen and progesterone receptors and lack of amplification of human epidermal growth factor receptor 2 (HER2) on tumor cells, which makes it particularly difficult to treat. Although only ~10-20% of all breast cancer cases, TNBC is particularly aggressive, and occurs more commonly in women younger than age 40, who are African-American, or who have a BRCA1 mutation. The 5-year survival rate is high (91%) if the disease is localized when first diagnosed, but decreases substantially (to 12%) if the tumor has already metastasized.

Due to the lack, or relatively small number, of relevant receptors, TNBC typically does not respond to hormonal therapeutics or agents targeting HER2. Chemotherapy has been the standard of care, although the benefits of this treatment are limited. Recently, however, three monoclonal antibody (mAb) therapies, atezolizumab (Tecentriq, Genentech Inc.), sacituzumab govitecan-hziy (TrodelvyTM, Immunomedics, Inc.), and pembrolizumab (KEYTRUDA, Merck & Co.) were approved by the US Food and Drug Administration (FDA) for TNBC. In addition, numerous other mAbs are in late-stage clinical study for this disease.

Atezolizumab is a humanized IgG1 mAb targeting programmed cell death protein 1 ligand (PD-L1) that was first approved by FDA for treatment of locally advanced or metastatic urothelial carcinoma in 2016. The Fc domain of atezolizumab was engineered by introducing an Asp to Ala change at position 298 in the CH2 domain of each heavy chain. Due to this alteration, the antibody devoid of N-linked oligosaccharides and does not have effector functions. On March 8, 2019, the FDA granted accelerated approval to atezolizumab in combination with paclitaxel protein-bound for adult patients with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] of any intensity covering ≥ 1% of the tumor area), as determined by an FDA-approved test. Approval was based on the placebo-controlled Phase 3 IMpassion130 (NCT02425891) study of 902 patients with unresectable locally advanced or metastatic TNBC who had not received prior chemotherapy for metastatic disease. In patients whose tumors express PD-L1, median progression-free survival was 7.4 months for patients receiving atezolizumab with paclitaxel protein-bound and 4.8 months for those receiving placebo with paclitaxel protein-bound. The objective response rate in patients with confirmed responses was 53% compared to 33% for the atezolizumab and the placebo-containing arms, respectively. Tecentriq is also approved in the European Union for treatment of TNBC.

Sacituzumab govitecan is an antibody-drug conjugate (ADC) comprising a humanized IgG1k antibody targeting TROP-2 fused to the active metabolite of irinotecan (SN-38). On April 22, 2020, FDA granted Trodelvy® an accelerated approval for adults patients with metastatic TNBC who received at least two therapies for metastatic disease. FDA’s approval was based on findings from the pivotal, single-arm clinical trial IMMU-132-01 (NCT01631552) that enrolled 108 previously treated patients with metastatic TNBC. The overall response rate was 33.3% and the median response duration was 7.7 months. Of the patients with a response to sacituzumab govitecan-hziy, 55.6% maintained their response for 6 or more months and 16.7% maintained their response for 12 or more month.

Pembrolizumab is a humanized IgG4 mAb targeting programmed cell death protein 1 (PD-1) that was first approved by FDA for treatment of melanoma in 2014. On November 13, 2020, FDA granted accelerated approval to pembrolizumab in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test. FDA’s approval was based on results from the Phase 3 KEYNOTE-355 study (NCT02819518) of patients with locally recurrent unresectable or metastatic TNBC, who had not been previously treated with chemotherapy in the metastatic setting. Median progression-free survival was 9.7 months in the pembrolizumab plus chemotherapy arm and 5.6 months in the placebo arm.

Other ADCs and antibodies that target PD-1 or its ligand (PD-L1) are undergoing evaluation in late-stage clinical study of TNBC patients, including the anti-HER2 ADC trastuzumab deruxtecan (Enhertu); anti-PD-L1 avelumab (Bavencio) and TQB2450; and anti-PD-1 serplulimab and toripalimab. More information about TNBC and antibody therapeutics for this disease can be found in these reviews:

Nagayama A, Vidula N, Ellisen L, Bardia A. Novel antibody-drug conjugates for triple negative breast cancer. Ther Adv Med Oncol. 2020 May 11;12:1758835920915980. doi: 10.1177/1758835920915980.

Won KA, et al. Triple‑negative breast cancer therapy: Current and future perspectives. Int J Oncol. 2020. PMID: 33174058.

Keep up to date on US and EU approvals all year by visiting our website!

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.

FDA approves Evkeeza (evinacumab-dgnb) for homozygous familial hypercholesterolemia

February 11, 2021 by Janice Reichert

On February 11, 2021, the US Food and Drug Administration approved Evkeeza (evinacumab-dgnb) injection as an add-on treatment for patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH), a genetic condition that causes severely high cholesterol. Evkeeza received orphan drug and breakthrough therapy designations for this indication, and the biological license application received a priority review.

Evinacumab is a human IgG4k antibody targeting angiopoietin-like 3 (ANGPTL3), which regulates the metabolism of plasma lipids, including low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides. The antibody was derived from Regeneron’s Velocimmune® technology platform, and includes a stabilizing mutation in the hinge region to minimize half-antibody formation.

Data from the Phase 3 ELIPSE trial (NCT03399786) was used as the basis of regulatory submissions. In this study 65 patients were randomized to receive either IV administration of evinacumab 15 mg/kg every four weeks (n=43) or placebo (n=22), plus other lipid-lowering therapies. The primary endpoint was the percent change from baseline in the LDL cholesterol level at Week 24. At baseline, LDL cholesterol was 260 mg/dL in the evinacumab group and 247 mg/dL in the placebo group. The primary endpoint of the study was met. Relative to baseline, the LDL cholesterol level at Week 24 was reduced by 47.1% in the patients administered evinacumab, but increased 1.9% in the placebo group.

Keep up to date on US and EU approvals all year by visiting our website!

Evinacumab is the first investigational (i.e., not previously approved for any indication) antibody therapeutic to be granted an approval in the EU or US in 2021. There are currently 17 investigational antibody therapeutics in regulatory review in the EU or US.