What are the differences between zanubrutinib vs ibrutinib？

zanubrutinib is an oral small-molecule inhibitor of Bruton's tyrosine kinase (BTK). Another BTK inhibitor that has been approved for marketing is ibrutinib. Coincidentally, the indications for zanubrutinib and ibrutinib are the same. So the two drugs are bound to be compared. Which is more effective, whose side effects are less, and whose prices are lower? Next, we will talk about them.

Comparison of therapeutic effects of zanubrutinib and ibrutinib

At the 2019 International Conference on Lymphoma (ICML), the Chinese scientific team published the results of clinical trials of zanubrutinib in the treatment of refractory recurrent sleeve cell lymphoma: an objective remission rate of 84%, and, alarmingly, a complete remission of 78%, meaning that malignant lymphocytes disappear. In 2013, clinical trial data for the treatment of refractory sleeve cell lymphoma were published with an objective remission rate of 68% and a complete remission rate of 21%.

Although the data for zanubrutinib and ibrutinib are not available in the same clinical trial and cannot be directly compared, the data for zanubrutinib are much higher and comparable than for ibrutinib. In particular, the rate of complete remission of zanubrutinib is almost four times that of ibrutinib, and the gap is very large.

Comparison of side-effects of zanubrutinib and ibrutinib

Direct clinical trials of zanubrutinib versus ibrutinib showed a significant difference in side effects. At the just-concluded American Clinical Oncology 2020 online meeting, Baekje Dhina released the latest data from its Phase 3 clinical trial of zanubrutinib versus ibutinib in treating patients with megomeginemia (WM).

The data showed a significant improvement in safety and tolerance compared to ibrutinib, and the overall risk of adverse events (AE) was lower, particularly in adverse events requiring special attention, such as atrial fibrillation (zebrinib 3.0% VS ibrinib 18.4%).

Comparison of prices of zanubrutinib and ibrutinib

To the patient, the price also is the main index that chooses anticancer drugs.

Ibrutinib costs $16,787 a month in the United States and $2,2680 a month in the country. Zanubrutinib costs $12,935 a month in the U.S., about 23 percent less than ibutinib costs in the U.S. Currently the domestic price of zanubrutinib has not been announced, but considering that zanubrutinib is a domestic drug, the price is expected to be lower than ibrutinib.

Comparison of the mechanism of action of zanubrutinib and ibrutinib

Quality comes from design. A good product is always "intentional", not just to achieve patent purposes.

First, the multikinase inhibitory activity of ibrutinib is considered to be responsible for its superior clinical efficacy, which is the rationale for multitarget drugs. However, for BTK, it depends on the level of research in translational medicine. Through animal experiments, BeiGene found that the efficacy of the drug depends on the inhibition of BTK, but is not related to other targets. At the same time, ibrutinib has begun to exhibit hemorrhagic, rash, and diarrhea adverse events. Targeting wild-type EGFR can cause skin toxicity and gastrointestinal adverse reactions.

Secondly, the first metabolic effect of ibrutinib was obvious. After 34%—73% ibrutinib was absorbed in the gastrointestinal tract, only 11%—25% reached the systemic circulation. Absolute bioavailability was only 2.9% and variability was high among healthy subjects.

Therefore, Dr. Wang Lai, Senior Vice President and Global R&D Director of BeiGene pointed out in an interview that ibrutinib's inhibition of the target is not complete, there are still many problems to be optimized. Selectivity and absorptivity are two strategies to optimize and improve product quality. The higher the selectivity, the smaller the potential side effects. The better the absorption, the lower the dose required to achieve the same target inhibition rate, further reducing toxicity and thus increasing the therapeutic window. It is not difficult to see that the selectivity and absorption of zanubrutinib were superior to that of ibrutinib at the beginning of the project.

Conclusion

To sum up, by comparing the differences between zanubrutinib and ibrutinib, zanubrutinib has certain advantages in the efficacy, side effects, prices, and mechanism of action. It is firmly believed that zanubrutinib will bring greater benefits to global patients. Considering both J&J and Albertville are known for their expertise in commercial operations, ibrutinib's market share is not going to be lost quickly. Let's wait and see what will happen in the BTKi market.