Emgality® ▼ (galcanezumab)

This information is intended for UK registered healthcare professionals only as a scientific exchange in response to your search for information. Please refer to the link for full prescribing information: Emgality Summary of Product Characteristics (SmPC)

Emgality® ▼ (galcanezumab): Carcinogenic Potential

Cases of malignant neoplasms that were reported during galcanezumab treatment in the phase 3 studies are summarized below. These were likely unrelated to galcanezumab treatment due to the short exposure time to galcanezumab prior to diagnosis

Detailed Information

Carcinogenicity

Nonclinical studies have not been conducted to evaluate the carcinogenic or mutagenic potential of galcanezumab. There is no evidence to suggest that chronic treatment with galcanezumab would increase the risk of carcinogenesis based on data from pharmacology and chronic toxicology studies with galcanezumab, as well as an assessment of the literature regarding CGRP.1

Consistent with the ICH guidance,2 carcinogenicity studies in animals were not scientifically justified.3 

Incidence of Malignancy in Phase 3 Migraine Prevention Clinical Trials

Across the galcanezumab placebo-controlled, phase 3 migraine prevention clinical trials, 6 cases of malignant neoplasms were reported as serious adverse events during galcanezumab treatment (Table 1).3

Two of the 6 cases were considered related to galcanezumab treatment by the investigator or by Eli Lilly and Company. Although similar events were not reported by patients on placebo, in view of the relatively short time interval between the start of galcanezumab treatment in these cases and the event onset, an association with galcanezumab is unlikely. Furthermore, the incidence of cancers of the breast, colorectum, and cervix uteri are among the highest reported in more developed regions globally.3

Table 1. Migraine Prevention: Cases of Malignant Neoplasms During Phase 3 Galcanezumab Treatment3

Preferred Term

Treatment

Event Onset

Potentially Related to Treatment by the Investigator or by Eli Lilly and Company

Adenocarcinoma of cervix

GMB 120 mg

6 months after first dose,
24 days since last dose of GMB.

No

Colon cancer

GMB 120 mg

1 month after first dose of GMB.

No

Tubular breast cancer

GMB 120 mg

1 month after first dose of GMB,
patient reported breast lump and
was subsequently diagnosed
with tubular breast carcinoma.

No

Lung neoplasm malignant

GMB 120 mg

18 days after fourth dose, patient reported cough which never resolved and was subsequently diagnosed as lung cancer 42 days after the last dose during the post-treatment phase.

Yes

Malignant nipple neoplasm

GMB 120 mg / GMB 240 mga

18 days after starting GMB, patient reported a wound on breast nipple that was subsequently diagnosed 9 months after beginning GMB as malignant.

Yes

Esophageal adenocarcinoma

PBO / GMB 240 mgb

243 days after starting GMB during open-label treatment (on the same day as 9th dose of GMB 240 mg), patient was hospitalized for esophageal carcinoma.

No

Abbreviation: GMB = galcanezumab; PBO = placebo.

a Patient received GMB 120 mg during double-blind treatment and GMB 240 mg during open-label treatment.

b Patient received PBO during double-blind treatment and GMB 240 mg during open-label treatment.

Note: The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose .1 The results of a maintenance dose of galcanezumab 240 mg once monthly are also described here. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

Description of Analysis Set

Randomized, Double-Blind, Placebo-Controlled Studies

The carcinogenic potential of galcanezumab was evaluated in phase 3 randomized, double-blind, placebo-controlled studies in adult patients for the prevention of

  • episodic migraine (EVOLVE-1 and EVOLVE-2),4,5 and

  • chronic migraine (REGAIN).6

The studies had a duration of

  • 6 months for prevention of episodic migraine,4,5 and

  • 3 months for prevention of chronic migraine, with an optional 9-month open-label extension phase.6 

Patients were randomized at the beginning of double-blind treatment in a 2:1:1 ratio to receive monthly subcutaneous injections of 

  • placebo

  • galcanezumab 120 mg with a loading dose of 240 mg, or

  • galcanezumab 240 mg.4-6 

This pooled analysis of 2886 adult patients included a total of 1435 patients that received monthly doses of galcanezumab (120 mg or 240 mg) administered subcutaneously.7

  • The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.1 Please note that the results of a maintenance dose of 240 mg galcanezumab once monthly are also included in this response. Even though this dose has been tested in pivotal studies, it has not been approved and therefore is not recommended.

The majority of patients were female (>80%) and Caucasian (>75%), with a mean age of 41 to 42 years.7

Open-Label Safety Study

Galcanezumab has also been studied in a phase 3, open-label, 12-month safety study for the prevention of episodic or chronic migraine.8

In this study, 270 patients were randomized to receive 12 monthly subcutaneous injections of 

  • galcanezumab 120 mg with a loading dose of 240 mg, or

  • galcanezumab 240 mg.8

References

1. Emgality [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.

2. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. 2011. Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals. S6(R1). http://www.ich.org/products/guidelines/safety/article/safety-guidelines.html. Accessed January 24, 2018.

3. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

4. Stauffer VL, Dodick DW, Zhang Q, et al. Evaluation of galcanezumab for the prevention of episodic migraine: the EVOLVE-1 randomized clinical trial. JAMA Neurol. 2018;75(9):1080-1088. http://dx.doi.org/10.1001/jamaneurol.2018.1212

5. Skljarevski V, Matharu M, Millen BA, et al. Efficacy and safety of galcanezumab for the prevention of episodic migraine: results of the EVOLVE-2 phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442-1454. http://dx.doi.org/10.1177/0333102418779543

6. Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine: the randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211-e2221. http://dx.doi.org/10.1212/WNL.0000000000006640

7. Stauffer VL, Wang S, Bangs M, et al. Phase 3 safety data from studies comparing galcanezumab and placebo in patients with episodic and chronic migraine. Poster presented at: European Academy of Neurology (EAN) – 4th Congress; June 16-19, 2018; Lisbon, Portugal.

8. Camporeale A, Kudrow D, Sides R, et al. A phase 3, long-term, open-label safety study of galcanezumab in patients with migraine. BMC Neurology. 2018;18(1):188. http://dx.doi.org/10.1186/s12883-018-1193-2

Glossary

CGRP = calcitonin gene-related peptide

ICH = International Conference on Harmonisation

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

Date of Last Review: February 19, 2019

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