On 15th, CHA Vaccine applied to the Ministry of Food and Drug Safety for a domestic phase 2 clinical trial plan (IND) for its shingles vaccine candidate "CVI-VZV-001." The company said that in a prior phase 1 trial, it confirmed not only safety but also efficacy, with antibody levels more than doubling in all participants.
Shingles occurs when the varicella-zoster virus (VZV), which causes chickenpox, lies dormant in the nervous system and reactivates when immunity declines. It is a common disease that causes skin rashes and severe neuralgia, and 1 in 3 people experience it at least once in their lifetime. Because shingles can cause extreme pain and leave complications once it develops, prevention is important.
Although shingles vaccines developed overseas are already on the market, post-vaccination pain and price burden are cited as drawbacks. Domestic corporations are challenging the dominance of global pharmaceutical companies and accelerating the development of next-generation shingles vaccines that reduce pain and expense.
While existing vaccines are made from the shingles virus itself, domestic corporations are developing next-generation genetic recombinant vaccines that administer only the virus's protein. The advantage is that side effects are fewer while the effect is similar. If commercialized, they are expected to target not only the domestic market but also overseas markets.
◇ Market shaken by MSD Zostavax withdrawal
Shingles vaccines currently 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 virulence of the live varicella-zoster virus. Representative products include Zostavax from U.S. Merck (MSD), the world's first shingles vaccine, and Sky Zoster from SK bioscience, a domestically produced vaccine.
Recombinant vaccines are made from specific proteins of the varicella-zoster virus. The virus gene is inserted into Chinese hamster ovary (CHO) cells and cultured, then the corresponding protein is purified. The virus protein produced in this way is injected into the human body to induce an immune response. Shingrix from U.K.-based GlaxoSmithKline (GSK), which currently dominates the market, is a recombinant vaccine.
Shingrix is a vaccine that enhances the immune response by combining an adjuvant (AS01B) with a specific protein of the varicella-zoster virus, and its preventive efficacy reaches 97%. Since receiving U.S. Food and Drug Administration (FDA) approval in 2017, it has maintained the No. 1 position in global sales. Zostavax has been pushed out of the market as its efficacy is relatively low and its immune effect declines in older adults, leading to supply discontinuations in many countries, including Korea.
In Korea, Sky Zoster, developed in-house by SK bioscience, entered the market in 2017. In Oct. last year, it captured more than half of the domestic live vaccine market as a spillover benefit from MSD's withdrawal of Zostavax. Sky Zoster requires only one dose, and its price is about one-third that of Shingrix (two doses, an average of 400,000 won). It also has the advantage of fewer side effects, such as arm pain and fever, after vaccination. Sky Zoster is currently undergoing regulatory procedures not only in Korea but also to expand into Southeast Asian markets.
However, the prevailing assessment is that the efficacy gap remains large to threaten Shingrix in the global market. Like Zostavax, Sky Zoster shows somewhat reduced preventive effect in immunocompromised patients and older adults. Last year, in domestic shingles vaccine sales, Shingrix ranked first with 42 billion won, while Sky Zoster and Zostavax recorded 18.7 billion won and 17.4 billion won, respectively.
◇ Targeting the limits of live vaccines with genetic recombination
Recently, domestic corporations have been accelerating the development of next-generation shingles vaccines that address the limitations of existing vaccines. Leading examples include shingles vaccines under development by GC Biopharma, CHA Vaccine, and EuBiologics.
The most advanced at present is GC Biopharma. Through its U.S. affiliate Curevo Vaccine, it is conducting a phase 2 clinical trial in the United States for the shingles vaccine candidate "Amezosvatein." In a head-to-head phase 2 trial with Shingrix, 100% of vaccine recipients showed an immune response, and adverse events were fewer than with Shingrix.
Curevo said it plans to complete the trial by next year and move straight into phase 3. GC Biopharma has taken on not only production of the clinical trial vaccines but also contract manufacturing (CMO) for future commercial volumes.
CHA Vaccine combined its proprietary adjuvant "Lipo-Pam" with the recombinant shingles vaccine candidate VZV-001. The company explained that Lipo-Pam induces a cellular immune response in which T cells directly destroy infected cells or cancer cells rather than antibodies, potentially compensating for the limited immune response in older adults seen with existing live vaccines.
The company said that while VZV-001 uses the same recombinant protein approach as Shingrix, its goal is to enhance the immune response while reducing post-injection pain and other side effects. A CHA Vaccine official said, "Looking at the detailed phase 1 data, VZV-001 showed far less pain than Shingrix," adding, "In phase 2, we will verify these aspects in detail."
EuBiologics is also developing a new vaccine platform based on its own protein synthesis technology. An industry official said, "Shingrix is unrivaled in terms of efficacy, but there are still gaps, such as price, storage conditions, and pain," adding, "If domestic vaccines target these niches, a shift in the market landscape is possible."
As shingles affects many patients, the market continues to grow. Global market research firm Grand View Research projected that the global shingles vaccine market will grow from $4.78 billion (6.67 trillion won) last year to $11.26 billion (15.7 trillion won) by 2030. With recent studies reporting that shingles vaccines may help prevent cardiovascular diseases such as myocardial infarction and stroke, as well as dementia, the market is expected to expand further.