Domestic Shingles Vaccine Reaches Major Milestone as Green Cross Bioscience Accelerates Commercialization
5On March 30, major positive news emerged regarding the domestically produced shingles vaccine!
LUZHU BIOTECH-B (02480.HK) has completed the Phase II clinical trial in China for its core product, LZ901. The trial results demonstrated statistical and clinical significance, along with a favorable safety profile. LUZHU BIOTECH expects to initiate an active-controlled Phase III clinical trial for LZ901 as soon as possible in 2023 and anticipates submitting a Biologics License Application (BLA) for LZ901 to the National Medical Products Administration (NMPA) in the second half of 2024.The herpes zoster vaccine is the R&D focus of LUZHU BIOTECH. LZ901, its latest advancement, is the first recombinant protein-based herpes zoster vaccine under development in China to complete Phase II clinical trials, which will also accelerate the commercialization process for LUZHU BIOTECH.
Announcement Information Further Discloses:
(1) In terms of immunogenicity studies, the geometric mean concentration (“GMC”), geometric mean titer (“GMT”), and seroconversion rate in the LZ901 high-dose group were significantly higher than those in the low-dose group. On the other hand, the antibody GMC, GMT, and seroconversion rate in both the LZ901 high- and low-dose groups were significantly higher than those in the placebo group; and
(2) In terms of safety, adverse events (“AEs”) in the trial mainly occurred within 0–7 days. The incidence rates of Grade 1, Grade 2, and Grade 3 AEs associated with the investigational vaccine were approximately 23.74%, 6.02%, and 1.00%, respectively. During the Phase II clinical trial of LZ901 conducted in China, no Grade 4 AEs or serious AEs were observed; and
(3) Phase II clinical trial data provided a solid basis for the Phase III clinical trial of LZ901. The dose for the Phase III clinical trial was determined to be 100 μg/0.5 mL/vial, and the immunization schedule should include two doses, with the second dose administered 30 days after the first dose.
In the previously announced Phase I clinical trial data, LZ901 also demonstrated favorable safety and efficacy.Data show that the likelihood of severe adverse reactions at the injection site of LZ901 is significantly reduced. The overall number and incidence of Grade I adverse events (AEs, i.e., vaccine adverse events) and Grade II AEs in subjects were far lower than those in subjects who received Shingrix, and no Grade III AEs were observed. Based on the immunogenicity data collected from the Phase I clinical trial,Compared with Shingrix, LZ901 induces a stronger cellular immune response. After the first dose of the vaccine, LZ901 can rapidly stimulate the body to produce higher levels of anti-VZV antibodies, demonstrating good immunogenicity.
In recent years, the uptake of herpes zoster vaccines among high-risk populations has accelerated. In 2022, Shingrix, the only herpes zoster vaccine available in China, saw its year-on-year sales growth exceed 100%. As the sole effective means of preventing herpes zoster, the vaccine’s popularity is rivaling that of HPV vaccines, positioning it as a product capable of reshaping the competitive landscape of the global vaccine market. However, the research, development, and manufacturing of herpes zoster vaccines are challenging; for companies seeking to enter this field, every step of the development process presents new trials.
2001In [Year], LUZHU BIOTECH was established in Beijing, dedicated to the research and development of innovative biological products. The founding team of LUZHU BIOTECH hails entirely from the renowned Beijing Institute of Biological Products under the Ministry of Health, which is the earliest institution in China engaged in microbiology and immunology research as well as the production of biological products, and has cultivated a large number of outstanding talents in the innovative development of biological products.
Among them, Kong Jian, co-founder of LUZHU BIOTECH, worked at the Beijing Institute of Biological Products under the Ministry of Health for over ten years, serving as Director of the Science and Technology Development Department and Head of the Immunodiagnosis Research Laboratory before leaving. Zhang Yanping and Jiang Xianmin, also members of LUZHU BIOTECH’s founding team, similarly hail from the Beijing Institute of Biological Products under the Ministry of Health. With decades of experience in the innovative development of biological products, they have accumulated extensive R&D expertise in the prevention and control of diseases with high prevalence among the Chinese population.
For many years, LUZHU BIOTECH has been deeply engaged in the research and development of recombinant protein technologies, independently developing technical platforms such as targeted recombinant antigen presentation. At its inception, with no vaccines available domestically or internationally for the prevention of epidemic cerebrospinal meningitis in children under two years of age, Kong Jian led the LUZHU BIOTECH R&D team to leverage their mastered polysaccharide-protein conjugation technology. They successfully developed five innovative bacterial polysaccharide-protein conjugate vaccines and low-pyrogen polysaccharide vaccines, significantly filling a market gap in disease prevention and control.
As LUZHU BIOTECH’s self-developed Fabite technology platform and mammalian expression technology platform continue to mature, the company’s innovative development of biological products has entered a new phase.
According to the prospectus, LUZHU BIOTECH has currently established a product pipeline comprising seven projects in development, including three vaccines (recombinant zoster vaccine, recombinant varicella vaccine, and recombinant rabies vaccine), one adalimumab biosimilar, and three bispecific antibodies (CD3/CD19, CD33/CD3, and CD19/CD3).
Of course, the recombinant zoster vaccine LZ901 is currently the most prominent star in LUZHU BIOTECH’s R&D pipeline.In the development of this vaccine, LUZHU BIOTECH optimized the molecular structure of the antigen and the formulation process, significantly enhancing the vaccine’s efficacy and safety. It is reported that LZ901, independently developed by LUZHU BIOTECH, is the first and only recombinant zoster vaccine in China seeking global regulatory approval.
It is understood that LZ901 features a redesigned antigen molecular structure, which can significantly enhance the in vivo immune response, thereby more effectively combating varicella-zoster virus (VZV) attacks on the body. Specifically, LZ901 is a fusion protein of the VZV glycoprotein E (gE) antigen and the Fc fragment of a human antibody, forming a tetrameric molecular structure. This structure resembles an immune complex and can bind more readily to Fc receptors on the surface of dendritic cells (DCs), resulting in higher antigen presentation efficiency.
In a previous media interview, Zhang Hui, CFO of LUZHU BIOTECH, stated that recombinant immune complex vaccines offer the advantage of active antigen presentation, capable of inducing robust humoral and cellular immune responses. In a sense, LUZHU BIOTECH has ushered in a new era in the field of recombinant protein vaccine technology and is achieving overtaking on a new track in the development of its recombinant zoster vaccine.
In addition, LUZHU BIOTECH has selected aluminum adjuvant, the most traditional and safest option, while avoiding the novel AS01B adjuvant containing immunostimulants, which is considered the key to Shingrix’s success.
For a long time, it has been widely believed within the industry that aluminum adjuvants are ineffective at inducing high-level T-cell immune responses. However, Phase I clinical trial data for LZ901 demonstrate that this recombinant protein antigen, with its modified molecular structure, when combined with an aluminum hydroxide adjuvant, not only induces higher neutralizing antibody titers but also elicits robust T-cell immune responses. In other words, if subsequent clinical trials of LZ901 proceed successfully, they will overturn established technical paradigms in the vaccine industry and have a profound impact on the future development of recombinant protein vaccines.
Shingles is a disease caused by a viral infection. Typically, shingles causes severe pain, with specific symptoms including pain, itching, or tingling in the affected area, followed by the development of a rash.
Beyond causing cutaneous discomfort, the greatest concern with herpes zoster lies in the potential for a series of severe complications. Among these, postherpetic neuralgia (PHN) is the most common complication of herpes zoster. Data indicate that approximately 9% to 34% of patients with herpes zoster are at risk of developing PHN. Furthermore, herpes zoster can lead to serious ocular complications, including blindness. In rare cases, it may also cause pneumonia, hearing impairment, encephalitis, and even death.
Globally, the incidence of herpes zoster is high among the elderly population and continues to rise. Data show that from 2015 to 2021, the number of new herpes zoster cases among individuals aged 50 and above in China increased from 2.5 million to 3.9 million, with a compound annual growth rate (CAGR) of 7.8%. This figure is projected to reach 4.9 million by 2025.
Another fact that cannot be ignored is that the shingles vaccination rate among people aged 50 and above in China remains extremely low. According to statistics, despite the introduction of GSK’s blockbuster shingles vaccine, Shingrix, the vaccination rate for this demographic in China was still a mere 0.04% in 2020.
Behind this,For a long time, the overall low maturity of the global herpes zoster vaccine market has been a key contributing factor.For many years prior to the launch of Shingrix, Merck’s Zostavax was the only shingles vaccine available globally. This live-attenuated vaccine demonstrated low protective efficacy and failed to achieve widespread adoption in the public health market. In October 2017, Shingrix was approved for marketing in the United States. As a recombinant protein vaccine utilizing a novel adjuvant system, Shingrix has significantly enhanced the effectiveness of shingles prevention.
ShingrixWith unstoppable momentum, it has triggered profound changes in the global herpes zoster vaccine market. In just its second year on the market, Shingrix ranked among the top sellers in the global top 10 vaccine sales list. Three years after Shingrix’s launch, Merck discontinued Zostavax in the United States. Meanwhile, numerous biopharmaceutical companies have actively developed their herpes zoster vaccine pipelines. However, as noted at the beginning of this article, the development of herpes zoster vaccines is extremely challenging. To date, only four herpes zoster vaccines have been launched globally: Merck’s Zostavax, GlaxoSmithKline’s Shingrix, SK Bioscience’s SkyZoster, and Baicai Biologics’ Ganwei. This limited product portfolio is clearly insufficient to meet the diverse vaccination needs of potential users worldwide.
However, the global penetration of Shingrix, as a blockbuster vaccine, has significantly raised public awareness of herpes zoster, accelerating the widespread adoption of herpes zoster vaccination.Research institutions predict that the domestic shingles vaccine market in China will experience significant growth between 2021 and 2025, with an estimated high compound annual growth rate (CAGR) of 103.8%, rapidly expanding to RMB 10.8 billion. By 2030, the market size for shingles vaccines in China is expected to exceed RMB 28.1 billion.
For innovative domestic enterprises developing herpes zoster vaccines, including LUZHU BIOTECH, the Chinese market for such vaccines is entering a golden period of growth. Accelerating the launch of products under development will undoubtedly generate substantial commercial value.As LZ901 successfully completes Phase II clinical trials and enters the pivotal Phase III stage, we have heightened expectations for the future performance of LUZHU BIOTECH as a leading domestic manufacturer of herpes zoster vaccines in China.