Empliciti
elotuzumab
Species
no relevantMonkey
Longest study
none
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Not conducted Not conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
None relevant; only a single-dose rhesus monkey study for off-target toxicity
“Due to the lack of a pharmacologically-relevant animal species to conduct toxicology studies, the scope of the toxicological evaluation for elotuzumab was limited to a tissue cross-reactivity study and in vivo studies that assessed the potential for off-target toxicity and local tolerance.”
Why that species
Binds only human CS1; no recognition of mouse or any nonhuman primate CS1 tested
“HuLuc63 specifically binds only to human CS1 and does not recognize CS1 from the mouse or any NHP species tested (see Figure 5).”
Surrogate molecule
No surrogate; human SLAMF7 transgenic mouse generated but judged not a valid toxicology model
“However, the mouse characterization results indicated that the human SLAMF7 transgenic mouse was not a valid alternative animal model for toxicology testing due to a lack of human SLAMF7 expression in both resting and activated T cells in this mouse model as compared to humans.”
Study lengthopen answer page →
Longest pivotal study
0 (no repeat-dose toxicity studies)
“Repeat-dose toxicity studies of elotuzumab were not conducted due to the lack of a relevant toxicology species or a valid transgenic mouse model.”
Pivotal GLP studies
No repeat-dose studies; single-dose IV rhesus monkey study (0, 30, 100 mg/kg), rabbit local tolerance, human TCR
“A single dose of intravenously infused elotuzumab (0, 30, or 100 mg/kg) was well tolerated in rhesus monkeys with no clinical signs at any dose.”
Route in tox
IV (30-minute infusion)
“In this study, elotuzumab was administered via continuous IV infusion over 30 minutes to 3 groups of rhesus monkeys (1 monkey/sex/group) at doses of 0, 30, or 100 mg/kg.”
Skipped studiesopen answer page →
Genotoxicity
Not conducted (ICH S6)
“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.”
Carcinogenicity
Not conducted (advanced cancer, ICH S9)
“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”
Reproductive & developmental
Not conducted (no pharmacologically relevant species)
“No reproductive and developmental toxicology studies were conducted due to the lack of a pharmacologically-relevant animal species.”
Safety pharmacology
Not conducted (no relevant species); no CNS or cardiovascular effects expected from SLAMF7 binding
“Binding to SLAMF7 by elotuzumab is therefore not expected to have effects on CNS parameters or cardiovascular functioning. The absence of specific safety pharmacology studies is therefore acceptable.”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Empliciti don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.
How it's usually set for oncology monoclonal antibodies (ICH S9)
In cancer patients the start dose should be pharmacologically active yet reasonably safe. A common small-molecule approach is one-tenth of the dose severely toxic to 10% of rodents, or one-sixth of the highest non-severely toxic dose in non-rodents.
“A common approach for many small molecules is to set a start dose at 1/10 the Severely Toxic Dose in 10% of the animals (STD 10) in rodents. If the non-rodent is the most appropriate species, then 1/6 the Highest Non-Severely Toxic Dose (HNSTD) is considered an appropriate starting dose.”
This product's starting point
NOAEL / key findings: Single IV doses of 30 or 100 mg/kg well tolerated in rhesus monkeys (EMA assessment report, p. 20)
NOAEL / key findings
Single IV doses of 30 or 100 mg/kg well tolerated in rhesus monkeys
“Single IV administration of elotuzumab at dose levels of 30 or 100 mg/kg (≤ AUC[INF] range of 335 to 447 mg•h/mL) were well tolerated.”
Risksopen answer page →
Immune & cytokine safety
In vitro human whole-blood assay: elevated levels of 10 cytokines with elotuzumab
“An in vitro cytokine release experiment identified elevated levels of 10 cytokines in response to elotuzumab treatment.”
Biodistribution & persistence
Human TCR: staining of plasma cells/immunoblasts in multiple tissues only; no staining of any nonhuman tissue
“In the human tissues examined, elotuzumab stained the membrane and/or cytoplasm of plasma cells and/or immunoblasts in the bone marrow, breast, cervix, esophagus, Fallopian tube, gastrointestinal tract, liver, lymph node, pancreas, salivary gland, small intestine, spleen, stomach, thymus, thyroid, tonsil, ureter, and uterus.”
Modality-specific risk
Human-specific target: no in vivo animal safety data, so safety characterization relies on clinical data
“Elotuzumab only recognizes human SLAMF7 protein. Because elotuzumab does not recognize non-human forms of SLAMF7 protein, in vivo safety data from animal studies are irrelevant.”