South Korean shingles vaccines target lower costs, fewer side effects

On the 15th of last month, Cha Vaccine Institute applied to the Ministry of Food and Drug Safety for a domestic phase 2 clinical trial plan (IND) for the shingles vaccine candidate 'CVI-VZV-001.' The company previously confirmed in phase 1 trials not only safety but also efficacy, with antibodies increasing more than twofold in all subjects.

Shingles occurs when the varicella-zoster virus (VZV), which causes chickenpox, reactivates after lying dormant in the nervous system when immunity weakens. It is a common disease causing skin rashes and severe neuralgia, affecting 1 in 3 people at least once in their lifetime. Shingles can cause extreme pain and leave complications, making prevention critical.

While shingles vaccines developed overseas are already on the market, their drawbacks include significant post-vaccination pain and high costs. Domestic companies are accelerating the development of next-generation shingles vaccines that reduce pain and costs, challenging the dominance of global pharmaceutical firms.

Existing vaccines are made from the shingles virus itself, but domestic companies are developing next-generation recombinant protein vaccines that administer only viral proteins. These vaccines offer similar efficacy with fewer side effects. If commercialized, they are expected to target not only the domestic market but also international markets.

◇MSD's Zostavax Exit Shakes the Market

Currently, shingles vaccines on the market are divided into two types: live attenuated vaccines and recombinant protein vaccines (inactivated vaccines). Live attenuated vaccines are made by weakening the toxicity of the live varicella-zoster virus. Representative products include Merck (MSD)'s 'Zostavax,' the world's first shingles vaccine, and SK Bioscience's domestic vaccine 'Skyzoster.'

Recombinant vaccines are made from specific proteins of the varicella-zoster virus. The virus's genes are inserted into Chinese hamster ovary (CHO) cells, cultured, and the proteins are purified. These viral proteins are then injected into the human body to induce an immune response. GSK's 'Shingrix,' which dominates the current market, is a recombinant vaccine.

Shingrix combines a specific protein of the shingles virus with an immune adjuvant (AS01B) to enhance immune response, achieving a 97% prevention efficacy. Since receiving U.S. Food and Drug Administration (FDA) approval in 2017, it has maintained the top global sales. Zostavax, with relatively lower efficacy and reduced immune effects in the elderly, has been phased out in many countries, including South Korea, and lost market share.

In South Korea, SK Bioscience's self-developed Skyzoster entered the market in 2017. Following MSD's withdrawal of Zostavax in October of last year, it captured over half of the domestic live vaccine market. Skyzoster requires only one dose and costs about one-third of Shingrix (two doses, averaging 400,000 Korean won). Its milder side effects, such as arm pain and fever, are also advantages. Skyzoster is currently undergoing approval processes for expansion into Southeast Asian markets.

However, experts assess that Skyzoster still lags behind Shingrix in efficacy. Like Zostavax, Skyzoster shows somewhat reduced preventive effects in immunocompromised patients and the elderly. Last year, Shingrix led the domestic shingles vaccine market with sales of 42 billion Korean won, while Skyzoster and Zostavax followed with 18.7 billion and 17.4 billion Korean won, respectively.

◇Overcoming Live Vaccine Limitations with Recombinant Technology

Recently, domestic companies have accelerated the development of next-generation shingles vaccines that address the limitations of existing vaccines. Notable candidates include those being developed by GC Biopharma, Cha Vaccine Institute, and EuBiologics.

GC Biopharma is currently leading the race. Through its U.S. subsidiary Curevo Vaccine, it is conducting phase 2 clinical trials in the U.S. for the shingles vaccine candidate 'Amezosvatein.' In a phase 2 trial directly comparing it to Shingrix, 100% of vaccinated subjects showed an immune response, with fewer side effects than Shingrix.

Curevo plans to complete the trial by next year and immediately proceed to phase 3. GC Biopharma is responsible for both clinical trial vaccine production and future commercial-scale contract manufacturing (CMO).

Cha Vaccine Institute combined its recombinant shingles vaccine candidate VZV-001 with its proprietary immune enhancer 'Lipo-Pam.' Lipo-Pam induces cellular immune responses, where T-cells directly destroy infected or cancerous cells, potentially overcoming the limitations of live vaccines in elderly immune responses, according to the company.

The company stated that while VZV-001 uses the same recombinant protein method as Shingrix, its goal is to reduce post-vaccination pain and other side effects while enhancing immune response. A Cha Vaccine Institute official said, "Phase 1 data shows VZV-001 causes significantly less pain compared to Shingrix," adding, "Phase 2 will confirm these aspects in detail."

EuBiologics is also developing a new vaccine platform based on its proprietary protein synthesis technology. An industry source said, "While Shingrix is unrivaled in efficacy, gaps remain in price, storage conditions, and pain issues," adding, "If domestic vaccines target these niches, market dynamics could change."

The shingles vaccine market continues to grow due to the high prevalence of the disease. Global market research firm Grand View Research estimated the global shingles vaccine market would grow from $4.78 billion (6.67 trillion Korean won) last year to $11.26 billion (15.7 trillion Korean won) by 2030. Recent studies suggesting shingles vaccines may prevent cardiovascular diseases like myocardial infarction and stroke, as well as dementia, are expected to further expand the market.

Korean Next-Gen Shingles Vaccines Challenge Global Dominance