Nanolec: Human papillomavirus (HPV) vaccine

The main articles are:

• Papillomaviruses
• Vaccines in Russia

2022: Approval for Phase 3 clinical trials in adult HPV vaccine patients

On June 27, 2022 biopharmaceutical , the company "" Nanolek announced that it had received from Ministry of Health of the Russian federation permission for phase three clinical trials in adult patients a vaccine against. HPV This will be the first domestic vaccine from HPV, which is planned to be brought to the market at the end of 2024. In 2 years, she must enter. National calendar of preventive vaccinations

The quadrivalent recombinant (types 6, 11, 16, 18) vaccine against HPV Nanolek is being developed in partnership with Combiotech with the purchase of full rights to the product.

The 3rd phase of the clinical trial of the first domestic HPV vaccine starts. Photo: pharmvestnik.ru.

The goal of the third phase of the clinical study is to evaluate the efficacy, immunogenicity and safety of the vaccine in a large sample of people - 440 participants, in contrast to the first phase, where several dozen volunteers are involved. During the last phase, it is easier to identify possible adverse events that are difficult to track in a small number of patients. commented Svetlana Zakirova, Deputy General Director of Nanolek for Development and Research

As part of the study, the domestic drug will continue to be compared with the Gardasil vaccine manufactured by Merck Sharp & Dohme (USA). At the first stage of the third phase, the vaccine will be tested on adults aged 18 to 45 years. The multicenter study will be held in several clinical centers: at the Kirov State Medical University, the Eco-Security Research Center (St. Petersburg), Perm State Medical University named after Academician E. A. Wagner, Medical and Sanitary Unit No. 163 of the Federal Medical and Biological Agency. After the completion of this stage, it is planned to continue the clinical trial of the third phase in children and adolescents 9-17 years old. When the results of the last stage of the study are received, the vaccine will be registered on the Russian market.

In 2021, the Russian HPV vaccine successfully passed the first phase of clinical examination, where it showed a more favorable safety profile and tolerability than the American reference drug - Gardasil. The second phase of clinical trials was not carried out: it is needed to select the dosage, and this is not required for generic vaccines (biosimilars).

The company plans to invest about 2 billion rubles in the development and full cycle of production of an HPV vaccine. 150 million of them are expected to be spent on clinical research by 2023. Another 600 million rubles will be spent on the development and scaling of production technology. The first Russian HPV vaccine will be produced in a full cycle, entirely from domestic raw materials, at the Nanolek plant in the Kirov region. To do this, the production building has been specially reconstructed, its layout and the concept of the case will meet the world standards of Good Manufacturing Practice, which establish requirements for production and quality control at pharmaceutical enterprises.

2021: Phase 1 Clinical Trial

The Russian biopharmaceutical The company Nanolek"" on November 22, 2021 reported the results of the 1st phase of the clinical trial, in which the vaccine from HPV its own development was compared with the vaccine of the same type produced in. USA The domestic drug showed a more favorable safety profile and better tolerability. Nanolek announced this on November 22, 2021.

Virus human papillomavirus (HPV) also causes cancer precancerous conditions, cervix vaginas, external female genitalia, penis and anus, as well as certain head and neck cancers in adults. According to published in to data 2021 in the scientific journal Lancet, vaccination against HPV by 90% reduces the risk of cervical cancer - a disease from which more than 300 thousand people die annually. This is a vaccination without age, but above WHO all recommends that girls from 9 to 13 years old, and among people 27-45 years old - primarily people living with HIV and smoking. The vaccine is already included in the national calendars of preventive vaccinations in 91, in country of the world Russia November 2021 it is included in separate regional vaccination calendars, it is planned to add it to the national calendar in 2024. So far, there are only foreign vaccines in civilian circulation.

The first phase of a clinical trial of a domestic HPV vaccine was carried out from July to November 2021 at the research center of the Kirov State Medical University. Two quadrivalent recombinant vaccines against human papillomavirus (HPV) were compared - domestic, which was developed by Nanolek in partnership with Combiotech, and American, manufactured by Merck Sharp & Dohme (USA). According to the results, the Russian drug showed a high tolerability and safety profile. The risk of adverse events was 7% lower than that of the reference drug, while all changes in the well-being of the subjects were mild - mainly reactions at the site of vaccine administration, for example, redness, itching and tenderness when pressed. The Russian vaccine also showed good immunogenicity: most volunteers developed antibodies to all four of the most common oncogenic strains after a single administration.

The first phase of the clinical trial confirms the high quality of the HPV vaccine, which our company is developing in partnership with Combiotech. For Nanolek, the creation and production of vaccines is a key priority, and we are proud that our portfolio will include another socially significant drug that can protect Russian women as much as possible from a common type of cancer, "says Vladimir Khristenko, President of Nanolek, adding that Nanolek plans to invest about 2 billion rubles in the development and full production cycle of the Russian vaccine.

The next phase of the trials is a randomized comparative clinical trial involving more than a thousand volunteers. And after that, Nanolek will move on to organizing industrial production.

We plan to bring it to market by 2024. In terms of production volumes, we will be ready not only to completely close the need for this vaccination in Russia, but also to export it, "said Maxim Stetsyuk, head of the vaccine division and first deputy general director of Nanolek. - We hope that in 2024 the HPV vaccine will be included in the national vaccination calendar, as is the plan of the state. In this case, all Russian girls from 9 to 13 years old will be able to receive this vaccination for free.

To assess the safety profile, the number of adverse events (AEs) - adverse changes in the subject's health status - was noted in the control groups. The risk of adverse events in those who tested the Russian vaccine was 7% lower: AEs were reported in 13% of volunteers, while in the group of subjects who received the reference drug - in 20% of volunteers.

In Group 1 (Russian vaccine), there were 60% of total injection site disorders and reactions (pain at the vaccination site, tenderness at pressure at the vaccination site, itching at the vaccination site), 20% of blood and lymphatic system AEs (regional lymphadenopathy), and 20% of reproductive AEs (menstrual disturbance). By intensity, 100% of AEs were attributed to mild severity. None of the volunteers required medication to treat AEs. In all AEs (100%), the outcome was "recovery/resolution without sequelae."

No clinically significant laboratory abnormalities were reported in any volunteer.

For the Phase 1 study, the immunogenicity assessment was not the primary objective and was of an additional nature. All volunteers who received the Russian vaccine became seropositive to all four types of HPV a month after a single vaccination. 100% of volunteers who received the reference drug became anti-HPV 6, anti-HPV 11, anti-HPV 16 seropositive, and 96.7% of volunteers became anti-HPV 18 seropositive.

At the same time, titer increase in group 1 (Russian vaccine) was observed for subtype 6 in 89.7% of volunteers, for subtype 11 - in 100% of volunteers, for subtype 16 - in 82.8%, and for subtype 18 - in 86.2% of volunteers. In group 2 (foreign drug), titer increase was observed for subtype 6 in 90% of volunteers, for subtype 11 - in 93.3% of volunteers, for subtype 16 - in 100%, and for subtype 18 - in 80% of volunteers.

The geometric mean antibody titer on the 28th day after vaccination in both groups was 4-30-fold higher depending on HPV type from baseline.

Thus, in serum samples taken on day 28 after a single vaccination with both the Russian vaccine and the reference drug, the increase in specific influenza antibodies in most volunteers to all four most common oncogenic strains was determined. The increase in antibodies to human papillomavirus of all types after vaccination with the studied vaccine and reference drug occurred in a similar way, which indicates the comparability of the intensity of the immune response in the compared drugs.