Russia’s biosimilar pembrolizumab: domestic innovation and patient access

The year 2022 brought significant disruption to many patients as foreign pharmaceutical companies pulled back and several clinical trials closed. This posed real challenges for the Russian healthcare system. Yet domestic pharmaceutical firms rose to the occasion, delivering new and original solutions. Russia now offers innovative developments and locally produced drugs for treating oncological diseases, along with successful introductions of generic therapies whose active substances mirror those of original drugs and have proven effectiveness in clinical studies.

Among these advances is the creation of a bioanalogue for pembrolizumab (trade name Pembroria®), a widely used oncology medication. It is employed to address a broad range of cancers, including melanoma, lung cancer, and renal cell carcinoma, among others.

Quality control

Biosimilars are a class of biologic medicines that resemble existing therapies. While often confused with generics, biosimilars and generics are distinct. Biosimilars originate from natural biological sources, a process that is intricate, lengthy, and costly. Generics, in contrast, contain low molecular weight compounds that can be reproduced via chemical synthesis. This fundamental difference shapes how they are developed and regulated.

Registration for biosimilars involves a sequence of extensive, costly comparative studies. Unlike unregistered generics, biosimilars undergo rigorous evaluation at all stages of clinical development to ensure safety and efficacy.

BioCAD conducted an extensive program to develop the pembrolizumab biosimilar, examining pharmacokinetics, pharmacodynamics, safety, and immunogenicity. Results demonstrated similarity between the original drug and the biosimilar, a finding that supported the equivalence of pembrolizumab BIOCAD and Merck & Co. Inc. (MSD). This provided the clinical basis for regulatory acceptance of the biosimilar in Russia.

After licensing and market launch, BIOCAD maintains ongoing pharmacovigilance to monitor safety and effectiveness. The pharmacovigilance service operates continuously in line with Russian legislation and international standards.

Drug independence

The introduction of a domestic biosimilar helps ensure a reliable drug supply for patients regardless of external sourcing, while also potentially reducing treatment costs for cancer patients. In its first year on the market, the biosimilar has demonstrated strong performance in clinical practice. Importantly, patients previously treated with foreign pembrolizumab now have the option to switch to the Russian biosimilar without compromising drug properties.

Currently, BIOCAD has launched REFLECTION, a non-interventional retrospective study assessing safety for patients with advanced cancers during the switch from the original drug to pembrolizumab biosimilar. The study also evaluates the biosimilar’s effectiveness in patients treated for six months or longer.

In a retrospective analysis of the electronic disease database from roughly 400 cancer patients across Russia, all participants received the original pembrolizumab (at least two injections) before switching to the biosimilar (also at least two injections).

Results indicate that the vast majority (98%) did not experience an increase in adverse reactions in frequency or severity, and overall adverse event rates did not exceed those seen with the original. About 88% of patients maintained disease control. These transitional efficacy and safety indicators suggest that the Russian pembrolizumab biosimilar could play a meaningful role in cancer treatment, particularly in ensuring continued access to life-saving therapy.

A parallel study is underway at the Moscow Scientific Research Center, led by AS Loginov, Doctor of Medical Sciences, Corresponding Member of the Russian Academy of Sciences, and Deputy Director. In a cohort of 114 patients with diverse malignant neoplasms, results supported the comparability of the biosimilar’s safety profile with the original drug. No increase in adverse reactions was observed during the switch.

As data collection progressed, most patients continued Pembroria® therapy and maintained disease control. No instances of biosimilar discontinuation due to adverse events were reported. These findings reinforce confidence in the biosimilar’s safety and practical viability.

Today BIOCAD produces all medicines within Russia, including the synthesis of pharmaceutical substances, ensuring continuity of drug therapy for Russian patients. This approach helps secure the future availability of essential medicines.

Medical supervision

Post-marketing studies gather additional information on effectiveness, safety, and side effects in real-world settings. They enable broader, longer-term monitoring of patients and verification of the drug’s impact on those with various comorbidities.

To broaden the evidence base for the biosimilar pembrolizumab in real-world clinical use, BIOCAD initiated a prospective multicenter study named PERFECTION. The study aims to evaluate the drug’s effectiveness and safety in patients with advanced cancer across multiple regions. It currently includes more than 160 patients with conditions such as metastatic non-small cell lung cancer, metastatic or unresectable head and neck squamous cell carcinoma, locally advanced or metastatic urothelial cancer, advanced renal cell carcinoma, metastatic or recurrent cervical cancer, and advanced endometrial cancer.

Interim data show no meaningful difference in safety between the biosimilar and the original pembrolizumab. Adverse event types and frequencies were comparable, including serious events.

Research on these programs continues, with results slated for publication in 2024. Such studies are highly important for clinicians and patients alike. The emerging evidence suggests Russian medicines can stand shoulder to shoulder with foreign developments, at times even surpassing them in real-world effectiveness.

Citations: Clinical program results and study notes are provided by BIOCAD and affiliated research centers where indicated (official study communications and internal reports disclosed for professional audiences). Independent evaluators and peer discussions corroborate these findings in context.