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FDA approves Beyfortus (nirsevimab-alip)

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On July 17, 2023, the U.S. Food and Drug Administration (FDA) approved Beyfortus (nirsevimab-alip) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants born during or entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Beyfortus is a human IgG1ҡ antibody targeting RSV. Developed by AstraZeneca and Sanofi, the Fc domain was engineered using AstraZeneca’s proprietary YTE half-life extension technology. One dose of Beyfortus, administered as a single intramuscular injection prior to or during RSV season, may provide protection during the RSV season.

Beyfortus has been granted special designations to facilitate expedited development by several regulatory agencies. These include Breakthrough Therapy Designation and Priority Review designation by The China Center for Drug Evaluation under the National Medical Products Administration; Breakthrough Therapy Designation from the U.S. Food and Drug Administration; access granted to the European Medicines Agency (EMA) PRIority MEdicines (PRIME) scheme and EMA accelerated assessment; Promising Innovative Medicine designation by the UK Medicines and Healthcare products Regulatory Agency; and has been named “a medicine for prioritized development” under the Project for Drug Selection to Promote New Drug Development in Pediatrics by the Japan Agency for Medical Research and Development.

Beyfortus has been granted marketing authorization in the European Union, Great Britain and Canada for the prevention of RSV lower respiratory tract disease in newborns and infants from birth through their first RSV season and is currently undergoing regulatory review in China, Japan and several other countries. In Canada, nirsevimab is also approved for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season, and such indication is under review at the EMA level.

The safety and efficacy of Beyfortus were supported by three clinical trials (Trials 03, 04 and 05). The key measure of efficacy was the incidence of medically attended RSV lower respiratory tract infection (MA RSV LRTI), evaluated during the 150 days after Beyfortus administration. MA RSV LRTI included all health care provider visits (physician office, urgent care, emergency room visits and hospitalization) for lower respiratory tract disease with worsening clinical severity and a positive RSV test. Trials 03 and 04 were randomized, double-blind, placebo-controlled, multicenter clinical trials.

Trial 03 (Phase 2b study, NCT02878330) included 1,453 preterm infants (born at greater than or equal to 29 weeks of gestational age up to less than 35 weeks of gestation) who were born during or entering their first RSV season. Of the 1,453 preterm infants in the trial, 969 received a single dose of Beyfortus and 484 received placebo. Among infants who were treated with Beyfortus, 25 (2.6%) experienced MA RSV LRTI compared with 46 (9.5%) infants who received placebo. Beyfortus reduced the risk of MA RSV LRTI by approximately 70% relative to placebo. The Beyfortus dosing regimen was determined based on further exploration of the Phase 2b data and was used in subsequent trials as a single 50 mg dose for those who weigh less than 5 kg, or a single 100 mg dose for those who weigh 5 kg or greater

For Trial 04 (Phase 3 MELODY study, NCT03979313), the primary analysis group within the trial included 1,490 term and late preterm infants (born at greater than or equal to 35 weeks in gestational age), 994 of whom received a single dose of Beyfortus and 496 of whom received placebo. The primary endpoint was met, reducing the incidence of medically attended RSV LRTD by 74.9% (95% CI 50.6, 87.3; P<0.001) compared to placebo. Among infants who were treated with Beyfortus, 12 (1.2%) experienced MA RSV LRTI compared with 25 (5.0%) infants who received placebo.

Trial 05 (Phase 2/3 MEDLEY study, NCT03959488), a randomized, double-blind, active (palivizumab)-controlled, multicenter trial, supported the use of Beyfortus in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. The trial enrolled 925 preterm infants and infants with chronic lung disease of prematurity or congenital heart disease. The safety and pharmacokinetic data from Trial 05 provided evidence for the use of Beyfortus to prevent MA RSV LRTI in this population.

References

Trial 03: Griffin MP, et al. Single-dose nirsevimab for prevention of RSV in preterm infants. N Engl J Med. 2020;383(5):415-425. doi: 10.1056/NEJMoa1913556.

Trial 04: Hammitt LL, et al. Nirsevimab for prevention of RSV in healthy late-preterm and term infants. N Engl J Med. 2022;386(9):837-846. doi:10.1056/NEJMoa2110275.

Trial 05: Domachowske J, et al. Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity. N Engl J Med. 2022;386(9):892-894. doi:10.1056/NEJMc2112186.

RYSTIGGO® (rozanolixizumab-noli) approved by FDA

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On June 27, 2023, the US Food and Drug Administration approved RYSTIGGO® (rozanolixizumab-noli) for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor or anti-muscle-specific tyrosine kinase antibody positive. Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor, resulting in the reduction of circulating IgG. The drug is administered by subcutaneous infusion. UCB has indicated that rozanolixizumab-noli will be commercially available in the US during the 3rd quarter of 2023.

FDA’s approval is supported by safety and efficacy data from the pivotal Phase 3 MycarinG study (NCT03971422), published in The Lancet Neurology in May 2023. The primary efficacy endpoint was the comparison of the change from baseline between treatment groups in the MG-ADL total score at day 43. MG-ADL is a measurement tool which assesses the impact of gMG on daily functions of 8 signs or symptoms that are typically affected in gMG, such as breathing, talking, swallowing, and being able to rise from a chair. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. A total score ranges from 0 to 24, with the higher scores indicating more impairment. A statistically significant difference favoring rozanolixizumab-noli was observed in the MG-ADL total score change from baseline [-3.4 points in rozanolixizumab-noli-treated group at either dose vs -0.8 points in the placebo-treated group (p<0.001)].

Interested in data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

Columvi® (glofitamab-gxbm) approved by FDA

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On June 15, 2023, the U.S. Food and Drug Administration (FDA) 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 1/2 NP30179 study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Glofitamab (RO7082859, CD20-TCB, RG6026) is a full-length IgG1λ/ҡ bispecific T cell-redirecting antibody targeting CD20 on malignant B cells and CD3 on T cells. This bispecific antibody was developed by Roche using the 2:1 CrossMab technology, characterized by 3 antigen-binding fragment (Fab) arms enabling monovalent binding to CD3ɛ and bivalent binding to CD20, with the second CD20 arm fused to the CD3ɛ-binding arms via a flexible linker. Glofitamab also features a heterodimeric Fc region engineered with PG LALA mutations to abolish binding to FcɣRs and C1q.

The FDA accelerated approval is based on positive results from the Phase 1/2 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 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 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.

Columvi received its first worldwide approval in Canada in March 2023, and the European Medicines Agency’s Committee for Medicinal Products for Human Use recently granted a positive opinion recommending its approval in the European Union.

Glofitamab is under investigation in a randomized, open-label, multicenter Phase 3 study (STARGLO, NCT04408638) where patients with relapsed or refractory DLBCL receive glofitamab or rituximab in combination with gemcitabine + oxaliplatin (GemOx). Patients will receive up to 8 cycles of glofitamab IV or rituximab IV in combination with GemOx IV followed by up to 4 cycles of glofitamab monotherapy. The primary outcome measure is overall survival. The estimated study primary completion date is in April 2025.

Interested in data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

FDA approves bispecific antibody EPKINLY™ (epcoritamab-bysp)

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On May 19, 2023, the US Food and Drug Administration approved EPKINLY™ (epcoritamab-bysp) for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from indolent lymphoma, and high-grade B‑cell lymphoma, after two or more lines of systemic therapy. Created using Genmab’s DuoBody® technology, epcoritamab (GEN3013, DuoBody®-CD3xCD20) is a T cell-engaging bispecific IgG1k/l antibody targeting CD20 and CD3 that is jointly owned by Genmab and AbbVie. EPKINLY was approved under FDA’s accelerated approval program based on response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial(s).

FDA’s approval was supported by data from the pivotal Phase 1/2 EPCORE NHL-1 trial (NCT03625037) studying epcoritamab in 157 patients with relapsed or refractory large B-cell lymphoma who had received at least two prior systemic therapies, including some who had received prior treatments with CAR-T cell therapy. The dose escalation findings from the Phase 1 part identified a dose of 48 mg as the recommended Phase 2 dose. In the Phase 2 part, patients received 48 mg of epcoritamab as 1 ml subcutaneous injections in 28-day cycles, with weekly dosing in Cycles 1-2, dosing every second week in Cycles 3-6, and dosing every 4 weeks from Cycle 7 onward. An overall response (complete or partial response) was seen in 61% (90/148 [95 percent confidence interval (CI): 52.5-68.7]) of patients and 38% (56/148 [95 percent CI: 30.0-46.2]) achieved complete remission. The median duration of response was 15.6 months (95 percent CI: 9.7-Not reached).

Epcoritamab is being investigated in multiple ongoing clinical studies across different settings and histologies. The most advanced of these is the randomized, open-label Phase 3 EPCORE™DLBCL-1 trial (NCT04628494) of epcoritamab vs investigator’s choice chemotherapy in patients with R/R DLBCL. The study is recruiting an estimated 552 patients and has an estimated primary completion date in June 2024.

Interested in data for other antibody therapeutics that have received marketing authorizations? Go to our searchable table of approved antibody therapeutics and those in regulatory review for more information.

FDA approves Zynyz™ (retifanlimab-dlwr) for Merkel cell carcinoma

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On March 22, 2023, the US Food and Drug Administration approved Zynyz™ (retifanlimab-dlwr) for the treatment of adults with metastatic or recurrent locally advanced Merkel cell carcinoma (MCC). Retifanlimab (INCMGA00012, MGA012) is a humanized, hinge-stabilized IgG4k antibody targeting PD-1. The biologics license application for Zynyz for MCC was approved under accelerated approval based on tumor response rate and duration of response.

FDA’s approval was based on data from the Phase 2 POD1UM-201 trial (NCT03599713), an open-label, multiregional, single-arm study that evaluated Zynyz in adults with metastatic or recurrent locally advanced MCC who had not received prior systemic therapy for their advanced disease. In this study, patients received Zynyz 500 mg intravenously every four weeks until disease progression, unacceptable toxicity, for up to 24 months. The primary endpoint was objective response rate (ORR) as determined by independent central radiographic review using RECIST v1.1. Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Among chemotherapy-naïve patients (n=65), Zynyz monotherapy resulted in an ORR of 52% (95% confidence interval [CI]: 40-65). Complete response was seen in 12 patients (18%), and 22 patients (34%) showed partial response. Among the responding patients, the DOR ranged from 1.1 to 24.9+ months; 76% (26/34) experienced a DOR of six months or longer and 62% (21/34) experienced a DOR of 12 months or longer by landmark analysis.

Incyte Corporation, which licensed retifanlimab from MacroGenics in 2017, is sponsoring clinical studies evaluating retifanlimab monotherapy as a treatment for other cancers, including endometrial cancer, non-small cell lung cancer, and squamous cell carcinoma of the anal canal.