Galcanezumab
Galcanezumab Uses, Dosage, Side Effects, Food Interaction and all others data.
LY2951742/galcanezumab is a fully humanized monoclonal antibody against human calcitonin gene-related peptide (CGRP) that is developed by ELi Lilly and Company. This therapy is given as a single subcutaneous injection twice a month and ongoing clinical trials for the agent are for episodic and chronic migraine as well as cluster headaches.
Although various small-molecule CGRP receptor antagonists have also been developed, humanized monoclonal antibodies like galcanezumab are specifically designed to potently and selectively bind to the CGRP entities directly. Given this target specificity, lack of off-target toxicity, and characteristic proteolysis profile of immunoglobulin antibodies to not undergo metabolism by liver enzymes, galcanezumab possesses favourable and promising safety and tolerability.
Galcanezumab was given FDA approval on 27 September 2018.
| Trade Name | Galcanezumab |
| Availability | Prescription only |
| Generic | Galcanezumab |
| Galcanezumab Other Names | Galcanezumab, Galcanezumab-gnlm |
| Related Drugs | Emgality, Trokendi XR, Reyvow, prednisone, propranolol, atenolol, topiramate, nifedipine, Depakote, sumatriptan |
| Weight | 100mg/ml, 120mg/ml |
| Type | Subcutaneous solution |
| Weight | 147000.0 Da (Approximate) |
| Protein binding | Readily accessible data regarding the protein binding of galcanezumab is not available. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Galcanezumab is a calcitonin-gene related peptide antagonist used to prevent migraines and treat cluster headaches.
Galcanezumab is a humanized monoclonal antibody that is indicated for migraine prophylaxis and treatment of episodic cluster headaches in adults by binding endogenous human calcitonin gene-related peptide (CGRP).
Galcanezumab is also used to associated treatment for these conditions: Episodic Cluster Headache, Migraine
How Galcanezumab works
Galcanezumab is a fully humanized monoclonal antibody designed and manufactured specifically against calcitonin gene-related peptide (CGRP). It binds avidly to human CGRP, with a binding affinity (Kd) of 31 pM (4.5 ng/mL).
Studies since 1985 have demonstrated that CGRP levels increase during acute migraine attacks in migraine-suffering patients but normalize after efficacious sumatriptan therapy. Moreover, research has also shown that intravenous administration of CGRP can induce migraine-like attacks in migraine-suffering patients. For all these reasons, the binding of CGRP to interfere with its activity was specifically designed to be the mechanism of action for galcanezumab to take advantage of in reversing the migraine-inducing activity of natural CGRP. The binding of galcanezumab to natural endogenous CGRP subsequently interferes with its activities, such as its binding to CGRP receptors, for example.
Studies have also shown that humanized monoclonal antibodies against CGRP have proven successful in reducing the frequency of migraine headaches in early clinical trials as a preventative therapeutic.
Toxicity
Overdose and LD50 date are not readily available.
The most common adverse effects associated with galcanezumab during clinical trials include headache, nasopharyngitis, hematuria, and contact dermatitis . However, with the exception of hematuria which was not present in placebo treatment arms, the frequencies of these events were similar to placebo . Additional frequently reported adverse effects in subjects receiving galcanezumab were diarrhea, toothache, and increased alanine aminotransferase (ALT) .
The pharmacokinetics of galcanezumab were not affected by age, sex, race, or subtypes of migraine spectrum (episodic or chronic migraine), based on a population pharmacokinetic analysis . Body weight has no clinically relevant effect on the pharmacokinetics of galcanezumab .
Renal and hepatic impairment are not expected to affect the pharmacokinetics of galcanezumab . Population pharmacokinetic analysis of integrated data from the galcanezumab clinical studies revealed that creatinine clearance did not affect the pharmacokinetics of galcanezumab in patients with mild or moderate renal impairment . Patients with severe renal impairment (creatinine clearance Label. Based on a population PK analysis, bilirubin concentration did not significantly influence the CL/F of galcanezumab .
Studies regarding the carcinogenic potential and genetic toxicology of galcanezumab have not yet been conducted .
When galcanezumab (0, 30, or 250 mg/kg) was administered to male rats by subcutaneous injection prior to and during mating, no adverse effects on fertility was observed . The higher dose tested was associated with a plasma exposure (Cave, ss) 8 times that in humans at the recommended human dose (RHD) of 120 mg . When galcanezumab was administered to female rats by subcutaneous injection in two studies (0, 30, or 100 mg/kg; 0 or 250 mg/kg) prior to and during mating and continuing throughout organogenesis, no adverse effects on fertility were observed . The highest dose tested (250 mg/kg) was associated with a plasma Cave, ss 38 times that in humans at the RHD .
Food Interaction
- Avoid alcohol.
- Take with or without food.
Volume of Distribution
The apparent volume of distribution of galcanezumab is documented to be 7.3 L, with 34% inter-individual variability.
Elimination Route
Following single dose subcutaneous administration, the time to maximum concentration was recorded as 5 days. The injection site location did not appear to significantly influence the absorption of galcanezumab.
The Cmax and the area under the concentration-time curve from dosing to infinity (AUC (0-∞)) are generally considered to be dose proportional over a dose range.
Half Life
The mean serum half-life of galcanezumab is similar at all dose levels at about 25-30 days. The elimination half-life of galcanezumab was ultimately approximately 27 days.
Clearance
It is noted that the clearance of galcanezumab is by proteolysis. The apparent clearance of galcanezumab was recorded as 0.008 L/h.
Elimination Route
Monoclonal antibody agents like galcanezumab are generally not eliminated via hepatic, renal, or biliary routes.
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