On the evening of January 31, BCHT Biotechnology announced that its zoster vaccine live had been approved for marketing, intending to prevent the herpes zoster infection in people over 40 years old, which is also the first approved herpes zoster vaccine made in China. The announcement notes that after obtaining the drug registration certificate, the zoster vaccine live also need to obtain the lot release certification and complete procedures such as the local access, making the time for marketing is not sure. Thus, the price of the vaccine has not been determined, and the clinical data has not yet been disclosed. Nevertheless, BCHT Biotechnology still kicks off the domestic substitution of the herpes zoster vaccine.

What is the herpes zoster? What are the technical routes for vaccine R&D? What's the current progress of R&D?

The market demand of the herpes zoster vaccine is huge

Herpes zoster (HZ) is an acute infectious skin disease caused by the reactivation of varicella-zoster virus (VZV) lurking in the body. When VZV is infected for the first time in childhood, it causes varicella. Then the virus enters the skin sensory nerve ending, moves to the center via the nerve fiber of the posterior root of the spinal cord or the trigeminal ganglion, and exists in the sensory ganglion of spinal nerve or cranial nerve for a long time in a persistent and latent form.

When the body has a low immunity or a nonspecific stimulation, the virus will be re-active, grow and propagate, causing the invaded ganglion inflammation or necrosis. Before the outbreak, the patients are characterized by low fever, discomfort, pain in the site where the rash will occur, and paresthesia; During the acute attack stage, the patients are characterized by rash and pain, blister on the unilateral skin surface, erythema, etc; During the chronic stage, the patients are characterized by persistent postherpetic neuralgia. According to the patients' description, the pain of postherpetic neuralgia is comparable to the labor pain and chronic cancer pain, which will last for weeks to years. The morbidity and severity of herpes zoster show a growth trend with the increase in age. About 70% cases of herpes zoster occur in the people over 50 years old.

At present, herpes zoster can not be treated by any specific medicine, and vaccine is the most effective prevention way. According to the consulting organizations, the herpes zoster vaccine market is forecast to reach RMB 56 billion in China in 2030, with a huge clinical need.

When Shingrix monopolizes the market with its excellent efficacy, how can BCHT Biotechnology stand out?

At present, only 3 kind herpes zoster vaccines are approved for marketing, that is MSD's Zostavax, GSK's Shingrix and SK's SkyZoster. Among them, SkyZoster is only sold in Korea.

Shingrix monopolizes the market with its excellent efficacy for its technical route and its self-developed new adjuvant AS01B, then how can BCHT Biotechnology's herpes zoster vaccine stand out?

According to the BCHT Biotechnology, its herpes zoster vaccine has the following advantages: (1) Applicable age is younger: People over 40 years old (it is over 50 years old for Shingrix); (2) One injection in the whole vaccination process, with high compliance (two injections for Shingrix); (3) Adverse reaction is low, with a better safety.

It is predicted that the revenue peak of BCHT Biotechnology's herpes zoster vaccine will reach about RMB 3.5-4.5 billion according to the current data of the active population of middle-aged and elderly people vaccinated with the flu vaccine.

The R&D status of herpes zoster vaccine in China

At present, in China, the enterprises with the herpes zoster vaccine can be mainly divided into two categories: One is the enterprises with live attenuation vaccine, including BCHT Biotechnology, Wantai BioPharm, Shanghai Biotechnology, etc, among which BCHT Biotechnology is in the fastest progress of this technical route. The other one is the enterprises with recombinant protein vaccine, including RECBIO, Immune-Path Biotechnology, Luzhu Biotech, Ab&B Bio-Tech, etc.

Among them, the Immune-Path Biotechnology is in the fastest progress. In 2020, the clinical trial application of its herpes zoster vaccine, the first domestic recombinant herpes zoster vaccine for clinical registration in China, was accepted by the National Medical Products Administration. In August 2021, Immune-Path Biotechnology's herpes zoster vaccine started the Phase I/II clinical trial.

The IND application of Luzhu Biotech's herpes zoster vaccine was accepted by NMPA in August 2021, starting the clinical trial formally. In June 2022, its herpes zoster vaccine started the Phase II clinical trial, being applicable to the susceptible adults over 40 years old.

Noticeably, RECBIO's recombinant herpes zoster vaccine, REC610, adopts its self-developed new adjuvant BFA01. In the preclinical head-to-head study, REC610 shows an immunogenicity (CD4+ T cells immune response), which is not inferior to the Shingrix, stimulating high levels of IL-2 and INF-gamma cytokines. In addition, on December 19, 2022, RECBIO announced that the clinical trial application of REC610 had been approved by Philippines for conducting the head-to-head clinical research together with Shingrix.

With the population aging and the increasing new herpes zoster cases, the herpes zoster vaccine's market's growth room in the future is still favored in China. But Shingrix's performance in China's market is not satisfactory comparing with the hot global market. In June2020, Shingrix was marketed formally in China, but its lot released doses were only 1.04 million during January to September in 2020. Due to the bad sale, GSK started to reduce the price, from the original RMB 1600/vial to RMB 1200-1300/vial. Nevertheless, the vaccination cost is still RMB 2400-2600 a year. Belonging to the Category II vaccine, Shingrix is a charged item, thus its sale is still "poor" after the price reduction. With the successive listing of herpes zoster vaccine made in China, we have reasons to believe that to realize domestic substitution is just a matter of time.

Key references:

1.  CDE official website;

2.  BCHT Biotechnology's Prospectus. Retrieved Jun 21, 2021, from http://data.eastmoney.com/notices/detail/688276/AN202106201498901785.html;

3.  Cell-mediated immune responses to a varicella-zoster virus glycoprotein E vaccine using both a TLR agonist and QS21 in mice.

About the Author:

Xiaobin

Xiaobin holds a Master's degree in Pharmacy and currently work as a public health control staff. Navigating through the intricate and complex data each day and feeling a sense of insignificance of herself. While being happy to witness the golden time of the development of Chinese bio-pharmaceutical industry. Hope to learn and improve together with everyone.