Which nonclinical studies did approved bispecifics skip?

“Standard genotoxicity studies are not considered appropriate for this class of biological product, in line with the ICH S6 (R1) guideline.”

“Carcinogenicity studies have not been performed with MCLA-128 as they are not considered appropriate for this class of biological product, in line with the ICH S6 (R1) and ICH S9 guidelines.”

“The Applicant did not conduct reproductive or embryo-fetal developmental toxicology studies with zenocutuzumab.”

“In vitro and in vivo genotoxicity studies were not performed in accordance with ICH S6 (R1).”

“As it is being developed for advanced cancer indications, no carcinogenicity studies have been conducted, in accordance with ICH S9.”

“Studies in mice using the surrogate showed no drug-related effects in male or female reproductive organs and did not reveal any embryo-fetal toxicity or teratogenicity.”

“genotoxicity studies have not been conducted with glofitamab. It is not expected that glofitamab would interact directly with DNA or other chromosomal material.”

“Carcinogenicity studies with glofitamab have not been conducted and are not planned. Glofitamab is intended for the treatment of patients with advanced cancer.”

“While no animal studies were conducted to assess the reproductive and developmental risks of glofitamab, a weight of evidence (WoE)-based risk assessment report was submitted.”

“Genotoxicity studies with elranatamab have not been conducted since they are generally not required for protein-based biotherapeutics per ICH S6(R1).”

“Carcinogenicity studies with elranatamab have not been conducted since they are generally not required for advanced cancer and protein-based biotherapeutics per ICH S9 and ICH S6(R1), respectively.”

“Embryofetal developmental toxicity was evaluated using a weight of evidence (WOE) risk assessment”

“Genotoxicity studies were not conducted for epcoritamab per ICHS6(R1) and ICH S9 guidance.”

“Carcinogenicity studies were not conducted for epcoritamab per ICHS6(R1), ICH S1A, and ICH S9 guidance.”

“An EFD toxicity study of epcoritamab in cynomolgus monkeys was waived for phase 3 trials and registration of epcoritamab across ICH regions (FDA, EMEA, and PMDA) given the high potential for immunogenicity of epcoritamab in cynomolgus monkeys.”

“Genotoxicity studies were not conducted as these types of studies are not applicable to biotechnology-derived pharmaceuticals (per ICH S6).”

“Carcinogenicity studies were not conducted due to lack of a pharmacologically relevant rodent species.”

“Animal reproductive and developmental toxicology studies were not conducted with emicizumab as hemophilia A is inherited in an X-linked recessive manner.”

“Therefore, no genotoxicity studies have been conducted or are planned, consistent with ICH Harmonised Tripartite Guideline S6”

“No carcinogenicity studies have been conducted nor are any planned in accordance with ICH S9 (ICH, 2010).”

“Two administrations of a tarlatamab surrogate, mus757, that binds mouse CD3 and DLL3, to pregnant mice on gestational days (GD) 6 and GD 13 did not result in maternal toxicity or embryo-fetal development toxicity at doses ≤4500 µg/kg.”

“Based on the biologic properties of tebentafusp, a fusion protein, genetic toxicology studies are not warranted.”

“Carcinogenicity studies were not warranted for the proposed indication.”

“Due to the specificity for human targets, embryo-fetal development (EFD) studies cannot be conducted in nonclinical species. Therefore, a weight of evidence assessment was conducted to evaluate the risk of tebentafusp administration on pregnancy and embryo-fetal development.”

“Genotoxicity studies have not been performed according to ICH S6(R1).”

“Standard carcinogenicity studies are generally inappropriate for biotechnology-derived pharmaceuticals according to ICH S6.”

“Studies to investigate reproductive and developmental toxicity have not been performed due to the lack of an appropriate animal species, the intended patient population with late-stage malignant disease.”

“In accordance with the current ICH guidance (ICH S6(R1) 2011), genotoxicity studies have not been conducted with mosunetuzumab because the potential of biotechnology products, in particular high molecular weight monoclonal antibodies, to elicit DNA damage in somatic or germ cells via electrophilic reactions is unlikely.”

“No carcinogenicity studies have been conducted with mosunetuzumab and are not planned for the intended oncology indication, as per Guidance for Industry S6R1.”

“A briefing book, including the WOE-based risk assessment and a request to waive a non-human primate embryo-fetal and prenatal/postnatal development study, was submitted to the FDA (dated 3 April 2018; Reference ID: 4277993).”

“No genotoxicity studies were conducted with linvoseltamab as antibodies are not expected to interact directly with DNA or other chromosomal material.”

“As linvoseltamab is intended for use in patients with advanced malignancies, carcinogenicity studies were not conducted with linvoseltamab, consistent with ICH S9 guideline Nonclinical Evaluation of Anticancer Pharmaceuticals.”

“The Applicant provided a weight of evidence (WOE)-based risk assessment to assess the potential for reproductive and developmental toxicities.”

“Antibodies, such as odronextamab, are not expected to interact directly with DNA or other chromosomal material. Therefore, no genotoxicity studies were conducted with odronextamab.”

“As odronextamab is intended for use in patients with advanced malignancies, carcinogenicity studies were not conducted with odronextamab”

“Embryo-fetal developmental toxicology studies with odronextamab were not conducted as such studies are expected to have limited value in further understanding and communicating risks to patients with advanced cancer.”

“Genotoxicity studies have not been submitted.”

“Carcinogenicity studies have not been submitted.”

“Reproductive and developmental toxicity studies have not been submitted.”

“Janssen did not conduct genetic toxicology studies as they are not appropriate for antibody therapies.”

“In addition, Janssen did not conduct dedicated studies to assess fertility or carcinogenicity as these studies are not necessary to support the development of a drug intended to treat patients with advanced cancer.”

“Rather than conducting a dedicated embryofetal development study, Janssen provided a weight-of-evidence-based assessment of the potential for amivantamab to cause reproductive and embryofetal toxicity.”

“Genotoxicity studies routinely conducted for pharmaceuticals have not been conducted and are not applicable to biotechnology-derived pharmaceuticals such as talquetamab per ICH S6.”

“As indicated in the ICH S9 guidance, carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer.”

“We agree with the Applicant’s WOE-based approach for the assessment of reproductive and developmental toxicity.”

“Genotoxicity studies were not conducted with teclistamab.”

“Carcinogenicity studies were not conducted with teclistamab.”

“No reproductive and developmental toxicity studies were conducted for teclistamab.”

“In accordance with ICH S6(R1) guidance, standard genotoxicity studies were not conducted with faricimab.”

“No standard rodent carcinogenicity studies have been conducted as faricimab showed no relevant binding to mouse or rat VEGF-A.”

“An embryofetal development (EFD) study in cynomolgus monkeys showed an increase incidence of abortions in faricimab treated monkeys at IV doses of 1 or 3 mg/kg administered weekly on gestation days 20 to 48.”

“Thus, mutagenicity studies are considered inappropriate and were not conducted.”

“Thus, given the intended patient population and lack of mechanistic concern, carcinogenicity studies are not planned with zanidatamab (ICH S9)”

“Consequently, the conduct of de novo developmental and reproductive toxicity (DART) studies is not warranted for zanidatamab.”