Which nonclinical studies did approved monoclonal antibodies skip?

“Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.”

“No long-term animal studies have been performed to establish the carcinogenicity potential of tocilizumab.”

“Genotoxicity studies are not considered relevant for a biological product in accordance with ICH S6.”

“Instead, a comprehensive risk assessment including feasibility assessment of available animal models for carcinogenicity testing was performed. Based on the weight of evidence the risk of carcinogenicity can be considered low.”

“Genotoxicity No studies have been performed in accordance with ICH S6(R1).”

“In line with ICH S6 (R1), a weight of evidence approach has been provided which suggests that there are no identified concerns for increased carcinogenic risk with the use of tralokinumab.”

“No genotoxicity studies of aducanumab were conducted because antibodies are generally unable to interact with genetic material.”

“Carcinogenicity studies of aducanumab were not conducted because its target, aggregated Aβ, is not present in wild-type rodents. No increases in the incidence or severity of proliferative lesions were observed in the 4-week study in monkey or the 13- or 26-week studies in aged Tg2576 mouse.”

“no genotoxicity studies have been conducted, in accordance with ICH S6(R1).”

“Carcinogenicity studies were waived, based on the lack of erenumab activity in rodents, histopathological data from the submitted toxicology studies showing no carcinogenic risk factors (i.e. hyperplasia or neoplasia)”

“According to ICH S6(R1), genotoxicity studies were not performed.”

“A thorough weight of evidence evaluation, in combination with data from the repeat dose toxicity studies, which included exposure to concizumab up to 52 weeks, does not suggest that concizumab has carcinogenic potential.”

“Genotoxicity studies with biologics such as garadacimab are not required.”

“Based on the weight of evidence, the Division agreed with the Applicant that a rodent carcinogenicity study was not technically feasible. Further, there appears to be a low or negligible carcinogenic potential based on the results of the 26-week monkey study and review of the published literature regarding chronic inhibition of FXIIa.”

“The lack of genotoxicity studies is considered justified according to ICH S6”

“2) ofatumumab is not pharmacologically active in rodents and so the standard carcinogenicity bioassays are unsuitable, 3) there is no scientific evidence to suggest that depletion of B cells by any other anti-CD20 therapeutics leads to cancer”

“No genotoxicity studies were performed.”

“No studies have been conducted to assess potential of bevacizumab for carcinogenicity or mutagenicity.”

“No genotoxicity studies were conducted. Belimumab is a monoclonal antibody and is not expected to interact directly with DNA or other chromosomal material.”

“CHMP concurred with the Applicant’s argumentation that the potential risk for malignancy with belimumab can only be evaluated in a clinical setting; the proposal for a clinical post-marketing safety study was supported.”

“No genotoxicity studies have been conducted. Since brolucizumab is an antibody fragment, the lack of genotoxicity studies is in accordance with the available guideline ICH S6 (R1) and this point is accepted.”

“Similarly, no carcinogenicity studies have been conducted with brolucizumab, as noted in ICH S6 (R1), standard carcinogenicity bioassays are generally not performed for biotechnology-derived pharmaceuticals.”

“Genotoxicity studies have not been conducted with nirsevimab. In accordance with ICH S6(R1), genotoxicity studies are not required for biologics as they are not anticipated to interact with DNA or other genetic material.”

“Carcinogenicity studies have not been conducted with nirsevimab. A weight of evidence approach was conducted in accordance with the FDA’s recommendations and applicable ICH guidelines for establishing the carcinogenic potential of nirsevimab and did not reveal any specific carcinogenic risk.”

“No genotoxicity studies have been conducted with bimekizumab in line with ICH S6 (R1) guideline.”

“In conclusion, the literature does not suggest a clear concern that inhibition of IL-17A and IL-17F would lead to carcinogenicity or tumor development.”

“Genotoxicity assays are not recommended for biological therapeutics. An Ames assay was conducted, and results were negative.”

“Carcinogenicity studies were not required because ublituximab is not active in rodent; therefore, standard carcinogenicity studies are not feasible.”

“In line with ICH S6(R1), genotoxicity studies are not considered relevant for proteins and were not performed with caplacizumab.”

“In line with ICH S6(R1), no carcinogenicity studies have been performed. No carcinogenic risk was identified based on the pharmacological mode of action, results from chronic dosing toxicity studies in Cynomolgus monkey (up to 26 weeks)”

“The lack of genotoxicity testing was considered acceptable, as in accordance with the ICH S6 guideline, the range and type of genotoxicity studies routinely conducted for pharmaceuticals are not applicable to biotechnology-derived pharmaceuticals and therefore are not needed.”

“The CHMP also considered acceptable that no carcinogenicity testing was performed, taking into account the lack of an appropriate animal model, the well-established risk of indirect tumorigenicity caused by prolonged immunosuppression”

“Certolizumab pegol was not genotoxic in the Ames test, the human peripheral blood lymphocytes chromosomal aberration assay, or the mouse bone marrow micronucleus assay.”

“No conventional carcinogenicity testing was performed with certolizumab pegol, which was acceptable considering the nature of the compound and the lack of pharmacological activity and immunogenicity of certolizumab pegol in species normally used for such testing.”

“Genetic toxicity studies were not applicable for this therapeutic biologic protein though reslizumab was negative in two in vitro assays.”

“A transgenic mouse (Tg.rasH2) carcinogenicity study was conducted with dose concurrence by the Executive Carcinogenicity Assessment Committee (ECAC). No drug-related neoplasms were found after dosing up to 500 mg/kg IV once every two weeks.”

“Based on the ICH Guideline for the Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals (ICH S6(R1) 2011), genotoxicity studies have not been conducted for secukinumab which is acceptable to CHMP.”

“Since secukinumab cannot be tested in a traditional 2-year rodent study to evaluate carcinogenic potential due to its species specific binding, the sponsor will monitor malignancy in psoriasis patients administered secukinumab as a part of a comprehensive Risk Management Plan.”

“Genotoxicity and carcinogenicity studies are generally not appropriate for biotechnology-derived monoclonal antibodies such as burosumab. No genotoxicity or carcinogenicity studies have been conducted by the Applicant; this is endorsed.”

“Overall, it is agreed that the carcinogenicity risk of burosumab appears to be low.”

“Y-mAbs has not conducted genetic toxicology studies with naxitamab. In accordance with ICH S6 and ICH S9, these studies are not considered necessary to support a marketing application for a biotechnology-derived pharmaceutical intended to treat advanced cancer.”

“Y-mAbs has not conducted carcinogenicity studies with naxitamab. In accordance with ICH S6 and ICH S9, these studies are not considered necessary to support a marketing application for a biotechnology-derived pharmaceutical intended to treat advanced cancer.”

“No genotoxicity studies were conducted with daratumumab (as per ICH S6) and no carcinogenicity were conducted with daratumumab (as per ICH S6 and S9).”

“ICH S9 also outlines that carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with advanced cancer, and as such no carcinogenicity studies were needed.”

“Genetic toxicology studies are not applicable to monoclonal antibodies and were not conducted with dupilumab based on ICH S6 guidance”

“No carcinogenicity studies were conducted. However, an assessment of the carcinogenic potential of dupilumab was made based on literature data on the role of the IL-4/IL-13 pathway in tumour development and on non-clinical data for both REGN646 and REGN1103.”

“Genotoxicity studies have not been conducted with ansuvimab-zykl. In accordance with International Council for Harmonisation (ICH) S6(R1), genotoxicity studies are not required for biologics.”

“In accordance with ICH S1A and ICH S6(R1), carcinogenicity studies are not required as ansuvimab-zykl will be administered as a single intravenous (IV) infusion.”

“Genetic toxicology studies are not applicable to monoclonal antibodies and were not conducted with lebrikizumab based on ICH S6 guidance.”

“There was no evidence of tissue proliferation (i.e., hyperplasia, pre-neoplastic lesions) or immunosuppression in the 9-month intravenous toxicology study in cynomolgus monkeys that received lebrikizumab doses up to 25 mg/kg/week. The overall data suggest that lebrikizumab has low carcinogenic potential.”

“Consistently with ICH S6(R1) guidance, genotoxicity studies were not conducted because galcanezumab is a monoclonal antibody.”

“Carcinogenicity studies were not required, based on the potential for galcanezumab to counter CGRP associated angiogenesis and immunosuppression, specificity of galcanezumab for CGRP, lack of structural alerts on galcanezumab”

“No genetic toxicology studies were conducted. Genetic toxicology studies are generally not necessary to support marketing of biotechnology-derived pharmaceuticals such as elotuzumab as discussed in the ICH S6 guidance document.”

“No carcinogenicity studies were conducted. Carcinogenicity studies are not necessary to support the marketing of therapeutics intended to treat patients with advanced cancer as discussed in the ICH S9 guidance document”

“No genotoxicity studies were performed with sutimlimab, as monoclonal antibodies are generally considered devoid of mutagenic or clastogenic risk.”

“Given the absence of proliferative lesions observed at either dose tested in the chronic monkey study and the lack of any identified tumorigenic risk based on the mechanism of action and a search of the relevant scientific literature, it is unlikely that sutimlimab possesses significant tumorigenic potential.”

“No genotoxicity studies of satralizumab were conducted because antibodies are generally unable to interact with genetic material.”

“Carcinogenicity studies of satralizumab were not conducted because satralizumab does not bind to rat or mouse IL-6R, and the use of a mouse homolog antibody was determined not to be feasible because of immunogenicity.”

“Genotoxicity studies were not conducted as vedolizumab is a humanized monoclonal antibody and so are not required in-line with ICH Guideline S6(R1).”

“In accordance with ICH Guideline S6(R1), conventional carcinogenicity studies (i.e., rodent bioassays) have not been conducted with MLN0002 to assess its carcinogenic potential as it lacks pharmacological activity in mice and rats.”

“the applicant decided to perform a partial genotoxicity study using in vitro and in vivo assays in terms of an AMES test and a rat micronucleus test. No genotoxic potential of Cetuximab was observed.”

“Based on the life-expectancy in the intended therapeutic indication, no long-term carcinogenisity studies are required80.”

“Genotoxicity testing was not performed. The product is a recombinant IgG2 protein of naturally occurring amino acids and is not expected to react with DNA or other chromosomal material.”

“A low incidence of osteosarcoma (2/54) was observed in high dose males at 19x human exposure. However, the lack of statistical significance of this finding and the large exposure multiple suggests that romosozumab is unlikely to increase the human risk of osteosarcoma.”

“no genotoxicity studies were performed with evinacumab, per ICH S6.”

“The Applicant submitted a weight of evidence carcinogenicity assessment for evinacumab based on available evidence from relevant literature and completed animal toxicology studies, which suggested that there is no identified risk of carcinogenicity for evinacumab.”

“No genotoxicity studies were conducted as monoclonal antibodies do not directly interact with DNA or other chromosomal material, which is in line with ICH S6(R1) guideline.”

“No carcinogenicity studies were conducted. The applicant conducted a weight-of-evidence (WoE) assessment to evaluate the potential of depemokimab to cause carcinogenicity.”

“Genetic toxicity studies were not applicable for this therapeutic biologic protein.”

“Carcinogenicity studies were not conducted since rodents are not pharmacologically relevant species. AstraZeneca submitted a carcinogenicity risk assessment that was evaluated by the CDER Executive Carcinogenicity Assessment Committee.”

“No genotoxicity studies were conducted with emapalumab as per International Conference on Harmonisation S6.”

“No carcinogenicity studies were conducted with emapalumab as per International Conference on Harmonisation S6.”

“Evaluation of the genotoxicity, carcinogenicity and dedicated safety pharmacology studies were not conducted and were not needed for this application.”

“The lack of carcinogenicity studies is considered acceptable based ICH S6 guidance.”

“The in-vivo test was a mouse micronucleus assay involving single iv injection of trastuzumab at 29.5, 59 and 118 mg/kg. All tests gave clearly negative results.”

“Herceptin has not been tested for carcinogenic potential.”

“No genotoxic effects were seen. This is not a complete genotoxicity test battery (see CPMP/ICH/174/95, S2B). However, for a monoclonal antibody, genotoxicity tests are considered to be of limited value and are therefore not needed (CPMP/ICH/302/95, S6).”

“No carcinogenicity study was performed with adalimumab. The lack of such studies is justified because there is no conventional or alternative model available, (i.e adalimumab has low/no affinity for mouse/rat TNFα, and MAHA developed after single doses).”

“As a monoclonal antibody, genotoxicity assessment of marstacimab was not scientifically appropriate and therefore was not conducted.”

“Based on the WoE provided by the Applicant, the Division agreed that marstacimab is unlikely to pose a significant carcinogenicity safety concern for humans and therefore considered a 2-year study in rats unlikely to provide additional useful information.”

“No genotoxicity studies were performed with canakinumab, as it is a protein. This is acceptable according to guideline ICH S6.”

“No carcinogenicity studies were performed with canakinumab. According to guideline ICH S6 carcinogenicity studies are generally not required for monoclonal antibodies.”

“No genotoxicity studies were performed, in line with ICH S6(R1).”

“Taken together the weight of evidence supports the position that tildrakizumab is unlikely to be associated with increased carcinogenic risk.”

“No genetic toxicology studies were conducted.”

“Nipocalimab is a mAb which does not cross-react with rodent FcRn, precluding the conduct of traditional carcinogenicity studies. In line with ICH guideline S6(R1) and based on a WoE approach it was concluded that nipocalimab does not pose an increased carcinogenic risk.”

“No genotoxicity studies were carried out.”

“No carcinogenitity studies were carried out.”

“No genetic toxicology or carcinogenicity studies were conducted or warranted to support this BLA submission, as dostarlimab‐gxly is a biotechnology‐derived pharmaceutical and the proposed indication is for advanced cancer.”

“No genetic toxicology or carcinogenicity studies were conducted or warranted to support this BLA submission, as dostarlimab‐gxly is a biotechnology‐derived pharmaceutical and the proposed indication is for advanced cancer.”

“Genetic toxicity studies were not applicable for this therapeutic biologic monoclonal antibody.”

“Based on species specificity, a rodent carcinogenicity study with sarilumab was not considered feasible. The Executive Carcinogenicity Assessment Committee (ECAC) concurred that a carcinogenicity study was not feasible.”

“Consistent with the ICH S6 guidance, genetic toxicology studies were not conducted or required for pembrolizumab.”

“Carcinogenicity studies were not required to support the licensing application for a product to treat advanced human cancer and are neither planned nor expected as post-marketing requirements at this time.”

“No genotoxicity studies of donanemab were conducted because antibodies are generally unable to interact with genetic material.”

“Carcinogenicity studies of donanemab were not conducted because its target, human AβN3pE-x peptide, is not present in wild-type rodents, and carcinogenicity studies in transgenic rodents are not feasible.”

“Studies evaluating genotoxicity of biotechnology products, are not mandatory in accordance with ICH S6 guideline”

“On March 19, 2014, the applicant was informed that a carcinogenicity assessment of lecanemab would not be necessary based on the development of neutralizing anti-drug antibodies in rodents treated with lecanemab or the mouse surrogate, mAb158.”

“Not conducted per ICH S6.”

“Carcinogenicity studies were not conducted or required to support the use of an antibody in the currently proposed indication per ICH S9.”

“There were no studies on genotoxicity or carcinogenicity. This is acceptable due to the nature of the compound.”

“Animal studies have not been conducted to determine the carcinogenic potential of ranibizumab.”

“Not performed per ICH S6(R1).”

“Not performed per ICH S6(R1), ICH S1A, and ICH S9.”

“Genotoxicity studies are generally not necessary to support marketing of biotechnology-derived pharmaceuticals such as tafasitamab as discussed in the ICH S6 guidance document.”

“Carcinogenicity studies are not necessary to support the marketing of therapeutics intended to treat patients with advanced cancer as discussed in the ICH S9 guidance document.”

“Genetic toxicology studies are not needed to support the development of nemolizumab, per the International Council for Harmonisation (ICH) S6(R1) guidance”

“There was no evidence of tissue proliferation (i.e., hyperplasia, preneoplastic lesions) or immunosuppression in the 6-month repeat-dose subcutaneous toxicity study in monkeys.”

“No formal genotoxicity studies for axatilimab have been conducted. Since monoclonal antibodies are not expected to interact directly with DNA”

“Because axatilimab is not active pharmacologically in rodents, conventional carcinogenicity studies in mice or rats are not relevant for axatilimab.”

“Genetic toxicity studies were not applicable for this therapeutic biologic protein.”

“The need for a carcinogenicity study was discussed with the Executive Carcinogenicity Assessment Committee and it was concluded that a carcinogenicity study was not required given the lack of related findings in the 6-month toxicology study in monkeys and since conduct of a study in rodents did not appear to be technically feasible.”

“Genetic toxicology studies were not conduct for ocrelizumab, consistent with ICH S6 guidance.”

“The sponsor submitted a carcinogenicity assessment waiver request under IND 100593 (Serial No. 0675, February 4, 2016). The waiver was granted”

“Not conducted, in line with ICH S6(R1).”

“In general, an overview of the published literature supports that neutralization of IL-23 would not be expected to increase cancer risk, but rather IL-23 increases tumor incidence and promotes tumor growth and progression.”

“The mutagenic potential of garetosmab-grts has not been evaluated; however, monoclonal antibodies are not expected to alter DNA or chromosomes.”

“a weight of evidence carcinogenicity assessment, and tissue cross-reactivity studies.”

“FDA agrees that genetic toxicology studies are not needed to support the use of penpulimab per ICH S6.”

“Carcinogenicity studies were not conducted with penpulimab, which is consistent with its use in patients with advanced malignancies (see the ICH Guidance S9).”

“There were no nonclinical genotoxicity or carcinogenicity studies performed with pertuzumab, as per the guidance provided in the International Conference on Harmonisation (ICH) guidance S6”

“According to ICH S6 (R1) guideline standard carcinogenicity bioassays are generally not appropriate for biotechnology derived pharmaceuticals and according to ICH S9 carcinogenicity studies are not warranted to support marketing for therapeutics intended to treat patients with late stage or advanced cancer.”

“No genotoxicity studies were conducted as crovalimab is a biotechnology-derived pharmaceutical.”

“Based on the mechanism of action, review of the literature, drug class, and the lack of drug-related preneoplastic lesions in monkeys administered crovalimab for up to 26 weeks, the risk of carcinogenicity of crovalimab is low. Crovalimab is not active in rodents; therefore, carcinogenicity studies are not feasible.”

“Consistent with the ICH S6 guidance, genetic toxicology studies were not conducted or required for necitumumab.”

“Carcinogenicity studies were not required to support the licensing application for a product to treat advanced human cancer”

“No carcinogenicity or genotoxicity studies have been conducted with idarucizumab.”

“Studies to evaluate the mutagenic and carcinogenic potential of idarucizumab have not been performed as based on its mechanism of action and the characteristics of proteins no carcinogenic or genotoxic effects were anticipated.”

“No studies were conducted. Denosumab is a recombinant protein and contains no inorganic or synthetic organic linkages or other non-protein portions.”

“No carcinogenicity studies were conducted in accordance with available regulatory guidance. Ovariectomized monkey treated for up to 16 months with denosumab showed no evidence of pre neoplastic lesions.”

“Genotoxicity tests are considered to be of limited value for this type of product. Still, a complete test battery has been performed. Infliximab did not show any genotoxic activity in these studies.”

“These data gave no support for the hypothesis that inhibition of TNFα is associated with an enhanced risk for tumour development.”

“Evolocumab is not expected to interact directly with DNA and mutagenicity studies were not conducted, per ICH-S6.”

“Evolocumab did not cause any drug-related tumors when administered to hamsters for up to 2 years in a lifetime carcinogenicity assay at doses administered once every other week that provide a 38-, 15- and 6.6-fold safety margin”

“The lack of reproductive, mutagenic, genotoxic and carcinogenic studies is justified, and SPC has been amended appropriately.”

“No long-term animal studies have been performed to establish the carcinogenic or mutagenic potential of RITUXAN or to determine potential effects on fertility in males or females.”

“No genetic toxicology studies were conducted.”

“Based on a weight of evidence assessment, conduct of carcinogenicity studies were deemed not necessary for UCB7665.”

“Genetic toxicity studies have not been conducted with anifrolumab. Genetic toxicity studies are generally not applicable for biotechnology-derived pharmaceuticals such as anifrolumab, as discussed in the ICH S6(R1) guidance document.”

“Carcinogenicity studies with anifrolumab were not conducted. Anifrolumab does not bind to murine IFNAR1 and does not inhibit the biological activity of murine IFN-α.”

“The FDA concurs with the Applicant that genotoxicity studies are not warranted per ICH guidance S6.”

“No fertility and early embryonic development, or carcinogenicity studies have been conducted or are warranted based on the proposed indication.”

“Based on ICH S6 (Guideline for the Safety Evaluation of Biotechnology-Derived Pharmaceuticals) guidelines, no genetic toxicology studies were conducted with brodalumab.”

“Therefore, it is impossible to know the carcinogenicity risk of brodalumab.”

“Genotoxicity studies as outlined in ICH S2B (1997) have not been conducted for golimumab.”

“No carcinogenicity study was performed with golimumab as standard rodent studies are not meaningful due to lack of pharmacologic activity in this species. However, with the current knowledge, a possible risk for the development of lymphomas or other malignancies in patients treated with a TNF-antagonist cannot be excluded.”

“Genetic toxicology studies were not needed to support the development and approval of risankizumab, per the ICH S6(R1) guidance.”

“Overall the risk for malignancy associated with long-term inhibition of IL-23 following administration of risankizumab to humans is considered to be low.”

“Genotoxicity and stand-alone safety pharmacology studies were not conducted.”

“there are no concrete reasons to believe that inhibition of IL36R by spesolimab would lead to carcinogenicity. The Executive Carcinogenicity Assessment committee (ECAC) concurred with this conclusion.”

“Genotoxicity tests were not conducted.”

“Direct evaluation of carcinogenic potential of CNTO 1275 (STELARA, ustekinumab) in carcinogenicity studies or rodent tumour immune surveillance models is precluded by the limited species reactivity of CNTO 1275 (STELARA, ustekinumab) which does not bind to or neutralise IL-12 or IL-23 from mice or rats.”

“Genetic toxicology studies were not conducted or needed per ICH S6 guidance.”

“Rodent carcinogenicity studies have not been conducted with siltuximab. Evidence from studies conducted with siltuximab and other IL-6 inhibitors suggest that the potential for siltuximab to cause carcinogenicity is low.”

“Carcinogenesis, mutagenesis, and reproductive toxicity studies have not been performed.”

“Carcinogenesis, mutagenesis, and reproductive toxicity studies have not been performed.”

“No genotoxicity studies have been performed for lanadelumab in accordance with ICHS6. This is considered acceptable.”

“The conduct of carcinogenicity studies in rodents was not feasible based on the development of ADA in SD rats after repeated dosing. Based on the results of the 39-week study in monkeys as well as evidence from the available scientific literature, chronic inhibition of bradykinin production via DX-2930 treatment is unlikely to affect carcinogenic risk in HAE patients.”

“Based on ICH S6 (Guideline for the Safety Evaluation of Biotechnology-Derived Pharmaceuticals) guidelines, no genetic toxicology studies were conducted with ixekizumab.”

“Thirdly, the literature does not suggest an increased risk for tumorigenicity in relation to neutralisation of IL-17. Overall, the carcinogenic potential of ixekizumab was considered to be low.”

“Genotoxicity studies have not been conducted, in accordance with ICH S6(R1).”

“Based on the mechanism of action and supporting literature, the risk of carcinogenicity can be expected to be low.”

“No studies have been performed to assess the potential of tislelizumab for carcinogenicity or genotoxicity in line with ICH guideline S9.”

“No studies have been performed to assess the potential of tislelizumab for carcinogenicity or genotoxicity in line with ICH guideline S9.”

“In line with the guideline on the pre-clinical safety evaluation of biotechnology-derived pharmaceuticals (ICH S6 R1), no genotoxicity studies were carried out.”

“The conduct of carcinogenicity studies in rodents was not feasible as tezepelumab does not bind to rodents’ TSLP. Therefore, a carcinogenicity risk assessment was conducted.”

“Genetic toxicology studies are not applicable to mAbs and were not conducted with guselkumab based on ICH S6R1 guidance”

“does not support a causal mechanistic/target-related link between IL-23 inhibition and increased cancer risk”

“As ibalizumab is a biotechnology-derived protein product made of natural amino acids, and as per ICH S6(R1), genotoxicity studies are not applicable and therefore have not been conducted.”

“The conclusion of this report made by the applicant was that given the weight of evidence, ibalizumab is not expected to be carcinogenic. Standard 2-year carcinogenicity studies in rodents or 6-month studies in transgenic mice were not possible, because ibalizumab does not bind rodent CD4.”

“There were no indications for a mutagenic potential as expected for a protein-like monoclonal antibody nor for potential contaminants or product excipients in the drug product.”

“Standard short or long term carcinogenicity studies were not performed due to the proteinous nature of the test article. Two in vitro and three in vivo studies were performed to study the effects the natalizumab on human α 4 expressing tumour cell lines in vitro and in vivo (as transplants into SCID and nude mice).”

“No genetic toxicology studies have been conducted with teplizumab or the surrogate.”

“The short duration of treatment, the absence of pharmacologic activity in the rodent (for teplizumab itself), and the observations of anaphylaxis and hypersensitivity following various dosing regimens in the rodent limit the utility of carcinogenic assessments”

“In line with ICH S6 (R1), genotoxicity studies were not performed with ALXN1210.”

“The carcinogenic potential of ALXN1210 in animals is unknown. However, in the 26‐week repeat dose toxicology study in mice with BB5.1, multiple hematopoietic neoplasms (lymphoma/lung/salivary glands/thymus) occurred in 1 high dose female (60 mg/kg/week)”

“Consistent with the ICH S6 guidance, genetic toxicology studies were not conducted or required for dinutuximab.”

“Carcinogenicity studies were not required to support the licensing application for a product intended to treat advanced human cancer”

“No genotoxicity studies were conducted, which is acceptable in accordance with ICH S6.”

“In accordance with the weight of evidence approach outlined in ICH S6 (R1), the applicant has presented argumentation for waiving of carcinogenicity studies.”

“Genetic toxicology studies with pozelimab have not been conducted, in accordance with ICH S6(R1).”

“Carcinogenicity studies with pozelimab have not been conducted. The Applicant conducted a carcinogenicity risk assessment for pozelimab and concluded that the carcinogenic potential is low.”

“Genotoxicity studies were not conducted for sibeprenlimab, a monoclonal antibody, which lacks the ability to directly interact with DNA.”

“A carcinogenicity risk assessment was submitted by the applicant, which was reviewed under the IND. Rodent carcinogenicity studies were deemed not to be warranted to establish an adequate assessment of carcinogenicity risk for sibeprenlimab.”

“Genotoxicity studies have not been conducted in accordance with ICH S6(R1).”

“Since blockade of CGRP would prevent these effects, the carcinogenic risk associated with eptinezumab is considered low.”

“A standard Ames test was negative. A full genotoxicity test battery and carcinogenicity evaluation have not been conducted for omalizumab, due to the absence of a relevant species appropriate for such studies.”

“No carcinogenicity study with omalizumab was performed since omalizumab does not bind rodent IgE.”

“No standard genotoxicity battery of studies was performed with ipilimumab.”

“considering the lack of relevance of the rodent species for ipilimumab, the limited value of short-term carcinogenicity studies with homologous products (as reflected in the draft reviewed version of the guideline), and the advanced condition intended to be treated by ipilimumab, the lack of conventional carcinogenicity studies is acceptable.”

“Genetic toxicology studies were not conducted because, as a monoclonal antibody, DAC HYP is not expected to interact directly with DNA.”

“Because DAC HYP is pharmacologically active only in monkey, carcinogenicity studies are not feasible; therefore, the carcinogenic potential of DAC HYP was not assessed.”

“No studies have been performed to test the potential of bezlotoxumab for carcinogenicity or genotoxicity.”

“No studies have been performed to test the potential of bezlotoxumab for carcinogenicity or genotoxicity.”

“Genetic toxicology studies were not warranted.”

“Carcinogenicity studies were not warranted.”