Author: Byung-Kun Kim

Promising real-world experience in South Korea

Byung-Kun Kim, Eulji University School of Medicine, Seoul, South Korea

Emgality (galcanezumab) was approved in South Korea in September 2019 and remains the only CGRP therapy available. Between December 2019, when it became available, and July 2020, I prescribed galcanezumab to around 200 patients, 55% of whom had chronic migraine, 40% episodic migraine (high frequency 31%, low frequency 9%), and 5% cluster headache.

I check the e-diaries and paper diaries that my patients use to track migraine attacks and have seen much greater improvement than reported in clinical trials, with 78% achieving a 50% or greater reduction in monthly migraine headache days. On the self-report measure of the Patient Global Impression of Change (PGIC) scale, 32% of patients said they were very much improved, 48% were much improved, 15% minimally improved, and 5% reported no change. No patients reported getting worse. Most patients said that their quality of life was much improved compared with oral preventive medication.

No patients have discontinued galcanezumab due to an adverse event. In my clinical practice, CGRP antibody therapy was much better tolerated than in clinical trials. In my experience, patients in clinical trials usually worried about even a minor adverse event such as injection site pain or rash. However, in clinical practice, they usually do not pay attention to trivial adverse events. Their main concern is whether treatment works or not.

If patients do not respond within three months, I do not usually recommend further injections because of the high cost.

To other clinicians in Korea, I would say that CGRP therapy is definitely a game changer. If your patients cannot tolerate oral preventive medication or do not respond to botulinum toxin, CGRP monoclonal antibodies are excellent alternatives and have significantly expanded the options for migraine therapy. More effective and better tolerated treatments may help improve the quality of life of migraineurs.

South Korea has a public healthcare system (National Health Insurance [NHI]) and optional private health insurance. NHI does not cover the cost of galcanezumab and private health insurance companies usually make partial reimbursement. Eli Lilly reimburses the cost of the first vial (about 400 USD) through its patient support programme, but physicians will need to discuss with patients about their private insurance plan for easy access to this expensive new therapy.

I understand that, in some countries, patients have been prescribed CGRP therapy instead of botulinum toxin because of restrictions on patients being able to attend clinics for injections. Korea has generally controlled COVID-19 well. However, some patients, who are reluctant to visit hospitals for fear of contacting the disease, are very happy with the galcanezumab autoinjectors.

Anti-CGRP therapy: what is its role in Korea?

In September 2019, Emgality (galcanezumab) became the first anti-CGRP therapy to be approved for migraine prevention in adults in Korea – a country with a migraine prevalence of 6.1% which is similar to other countries in Asia.1 Clinical trials of Aimovig (erenumab) and Ajovy (fremanezumab) are nearing completion, with approvals expected in 2021. Byung-Kun Kim, Professor of Neurology at Eulji Medical School, Seoul, discusses the role of anti-CGRP therapy in Korea.

 

  1. Which patients in Korea should be considered for anti-CGRP therapy and what dose do you advise?

As there is no restriction on prescribing galcanezumab for migraine prevention in Korea, it could be used as first line treatment. However, considering its high cost, physicians usually prescribe galcanezumab to patients who fail on current oral preventive medication due to lack of efficacy, suboptimal efficacy, or intolerability. We also need to consider contra-indications to other drugs used for migraine prevention, for example, propranolol is contraindicated in asthma, and a history of renal stones is a relative contraindication to topiramate. Of course, the preferences of the patient are also important. I advise using the same dosage regimen for galcanezumab as in clinical trials – 240 mg once as a loading dose, followed by 120mg monthly.

  1. Have studies been carried out specifically in Korean patients and what did they show? Is there any evidence of different efficacy, pharmacokinetics or side effects in Korean patients?

Korean patients took part in both the pivotal EVOLVE-2 study of galcanezumab in episodic migraine2 and the more recently reported CONQUER study in patients with treatment resistant migraine.  When we analysed the results of the EVOLVE-2 study, the efficacy of galcanezumab in patients from Korea was highly consistent with the primary study cohort.  In addition, the safety profile was consistent with that seen in other Phase 3 migraine studies of galcanezumab, including the primary study cohort in EVOVE-2. There was no difference in immunogenicity in the Korean population.

A clinical trial of fremanezumab in episodic and chronic migraine is ongoing for regulatory approval in Korea and Japan. Korean patients are also participating in a clinical trial of erenumab in episodic migraine (EMPOwER) to support regulatory approval, and the DRAGON trial in chronic migraine is underway in Korea.

  1. What should clinicians in Korea tell patients about anti-CGRP therapies before they prescribe them?

Migraine is a highly prevalent disease and may be experienced by women throughout their child bearing years. Owing to the month-long half life of CGRP monoclonal antibodies (MAbs), we should carefully discuss pregnancy planning with patients before initiating treatment with MAbs. In our practice, we advise discontinuation at least five months before conception.

  1. What new research would you like to see on anti-CGRP therapies?

We are expecting a lot of new research on anti-CGRP therapies in Korea, including in pregnancy, in adolescents and in post-traumatic headache. We are also expecting a cardiovascular disease registry to be established for MAb therapy and long term safety studies of more than five years’ treatment duration. A clinical trial of the oral CGRP receptor antagonist, atogepant, is expected to get underway at the end of 2019.

  1. Do patients in South Korea have to pay for anti-CGRP therapies or are they included in any free health service or by insurance?

South Korea has a public healthcare system (National Health Insurance [NHI]) and optional private health insurance. Public healthcare is financed in a similar way to other nations with public healthcare – through national insurance based on individual earnings. The NHI system is compulsory and required by Korean law. However, NHI does not cover the cost of galcanezumab. Fortunately, most people in Korea have their own private health insurance, and private health insurance companies in Korea reimburse part or all the medical expense depending on the contract. There is no restriction on reimbursement as long as patients are migraineurs.

References

  1. Byung-Kun Kim, Min Kyung Chu, Te Gyu Lee et al. Prevalence and Impact of Migraine and Tension-Type Headache in Korea. J Clin Neurol. 2012 Sep; 8(3): 204–211.
  2. 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. Cephalgia 2018 Jul;38(8):1442-1454.