November 22, 2021. The Russian biopharmaceutical company Nanolek announces the results of the 1st phase of a clinical trial aimed at comparing a new HPV vaccine developed in-house with a vaccine of the same type produced in the USA. The domestic drug showed a more favourable safety profile and better tolerability.

Human papillomavirus (HPV) causes cancers and precancerous conditions of the cervix, vagina, external female genitals, penis and anus, and some head and neck cancers in adults. According to findings published in 2021 in the Lancet scientific journal, HPV vaccination lowers by 90% the risk of cervical cancer, a disease that kills more than 300,000 people every year. This vaccine does not relate to a particular age, but WHO recommends vaccinating girls from 9 to 13 years old and people aged 27-45, in particular those living with HIV and smokers in the first place. The vaccine has been included in the National vaccination schedules in 91 countries worldwide. Now it is included in some regional vaccination schedules in Russia, and is expected to be added to the National schedule in 2024. Up to date, only foreign vaccines have been put into the stream of commerce.

The first phase of a clinical trial of a new domestic HPV vaccine was carried out from July to November 2021 at the research center of Kirov State Medical University. Two quadrivalent recombinant vaccines against human papillomavirus (HPV) were compared — a domestic vaccine developed by Nanolek in partnership with Kombiotech, and the American one, manufactured by Merck Sharp & Dohme (USA). According to the findings, the Russian medication showed a high tolerability and safety profile. The risk of adverse events was 7% lower than that of the reference drug, while all the changes in the subjects’ well-being were mild - these were chiefly reactions at the place of injection, e. g. redness, itching, and/or pain on palpation. The Russian vaccine also showed good immunogenicity: most volunteers developed antibodies to all four of the most common oncogenic strains after a single injection.

“The first phase of the clinical trial confirms the high quality of the HPV vaccine that our company is developing in partnership with Kombiotech. For Nanolek, the development and production of vaccines is a key priority. And we are proud that another socially important medicine will enhance our portfolio to ensure the highest possible protection of Russian women from the common type of cancer,” says Vladimir Khristenko, president of Nanolek, adding that Nanolek plans to invest about 2 billion roubles in the development and entire production cycle of the Russian vaccine.

The next phase of trials is a randomized comparative clinical trial involving more than a thousand volunteers. And only then Nanolek will proceed to efforts towards setting up a production facility.

“We plan to launch it on the market by 2024. In terms of production volumes, we are going to completely cover the need for this vaccine in Russia and also produce it for export,” said Maksim Stetsyuk, Head of the vaccine division and First Deputy General Director at Nanolek. “We hope that the HPV vaccine will be included in the National vaccination schedule later this year, as the government plans. In this case, all Russian girls aged 9 to 13 will be able to receive a vaccine shot free of charge.”

Clinical Trials of the First Domestic HPV Vaccine

Tolerability and Safety. To assess the safety profile in control groups, the number of adverse events (AE) was measured — negative changes in the health condition of the subjects. The risk of adverse events in those who tested the Russian vaccine was 7% lower: AEs were observed in 13% of volunteers, whereas in the group of subjects exposed to reference drug - in 20% of volunteers.

In group 1 (Russian vaccine), 60% of general disorders and reactions at the place of injection were communicated (pain at the place of injection, pain on palpation, and itching at the vaccination place), 20% of AEs were observed in the blood and lymphatic system (regional lymphadenopathy) and 20% of AEs accrued to the reproductive system (menstrual irregularities). In terms of intensity, 100% of AEs were classified as mild. None of the volunteers was in need of drug therapy to eliminate the AEs. In all cases of AEs (100%), the outcome was “recovery/comeback without consequences.”

Clinically significant deviations of laboratory parameters from the norm were not registered in any of the volunteers.

Immunogenicity

For the first trial phase, immunogenicity assessment was not the primary task and was supplementary. All volunteers who received the Russian vaccine became seropositive for all four types of HPV one month after a single vaccination. As many as 100% of the volunteers who received the reference drug became anti-HPV 6, anti-HPV 11, anti-HPV 16 seropositive, and 96.7% of the volunteers became anti-HPV 18 seropositive.

At the same time, rising antibody titers in group 1 (Russian vaccine) was the case 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), rising antibody titers were 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 average geometric titer of antibodies on the 28th day after vaccination in both groups was 4–30 times higher, depending on the HPV type, relative to the baseline level.

Thus, in serum samples taken on the 28th day after a single vaccination with both the Russian vaccine and the reference drug, showed an increase in specific influenza antibodies in the majority of volunteers against all four most common oncogenic strains. The rising antibodies against human papillomaviruses of all types after vaccination with the tested vaccine and the reference drug occurred similarly, which is an indication of the comparability of the intensity of the immune response in the compared drugs.

About Nanolek: a modern biopharmaceutical company founded in 2011 by Vladimir Khristenko and Mikhail Nekrasov, specializing in the production of import-substituting and innovative drugs, both developed in-house and created with international partners. Nanolek is one of the leaders in the production of pediatric vaccines in the Russian Federation. In addition to vaccines, the Nanolek’s portfolio includes drugs to treat HIV, cancer, and orphan diseases.