On June 26, 2023 AB Science SA (Euronext-FR0010557264-AB) reported that the European Patent Office has issued a Notice of Allowance for a patent relating to methods of treating (mCRPC) with its lead compound masitinib, based on findings from study AB12003 [1] (Press release, AB Science, JUN 26, 2023, https://www.ab-science.com/ab-science-receives-notice-of-allowance-for-european-patent-covering-masitinib-in-the-treatment-of-metastatic-castrate-refractory-prostate-cancer-mcrpc/ [SID1234632886]). This new European patent provides intellectual property protection for masitinib in the treatment of mCRPC until 2042.

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Masitinib is positioned in combination with docetaxel as a treatment of mCRPC patients who are eligible to chemotherapy; that is to say, it is administered directly following the metastatic hormone-sensitive prostate cancer (mHSPC) treatment space.

Although there are numerous treatments in the mHSPC treatment space, there is currently no drug registered for use in combination with docetaxel in patients with mCRPC, despite docetaxel having been approvedalmost 20 years ago. Historically, there has been a high failure rate of trials studying combinations of docetaxel and new targeted agents, with study AB12003 being a rare example of a phase 3 clinical trial that showed improvement in progression-free survival (PFS) for masitinib in combination with docetaxel.

The Notice of Allowance (NOA) means that the European Patent Office intends to grant the patentapplication, EP4175639A1, after the completion of certain formal procedural steps. Once granted, the patent can be kept in force until May 2042. A European NOA is issued after an examiner determines that a patent application satisfies all requirements for patentability under the European Patent Convention.

More specifically, this patent provides protection of masitinib and related compounds for treatment of mCRPC in a patient subpopulation with low metastatic involvement (as measured by baseline alkaline phosphatase levels). This patient population is fully consistent with results from masitinib study AB12003 [1] and the on-going clinical development program of masitinib in mCRPC. As a reminder, key results from study AB12003 include:

Masitinib (6.0 mg/kg/day) plus docetaxel conferred a significant progression-free survival (PFS) benefit in mCRPC patients with baseline alkaline phosphatase levels (ALP) less than or equal to 250 IU/L; hazard ratio of 0.79 [0.64,0.97] (p=0.0087), corresponding to a 21% reduction in risk of progression relative to control.

Assessment of PFS rates was convergent with this primary outcome, with 12, 18, and 24-month PFS rates showing significant improvement in favor of masitinib plus docetaxel relative to control: 1.6-fold (p=0.0035), 1.9-fold (p=0.0001) and 1.9-fold (p=0.0028), respectively.

A progressively greater masitinib treatment effect was observed for lower baseline ALP levels (i.e., less advanced metastatic disease), with a significant 47% reduced risk of progression in patients with ALP less than or equal to 100 IU/L (hazard ratio=0.53, p=0.002).

The masitinib plus docetaxel safety profile was acceptable, consistent with the known masitinib profile and with no new safety signals observed.

Although localized disease is associated with high survival rates, metastatic prostate cancer still represents an unmet medical need with a 5-years survival rate of about 32%.

References

[1] Pavic, Michel; Hermine, Olivier; Spaeth, Dominique LBA02-11 Masitinib plus docetaxel as first-line treatment of metastatic castrate refractory prostate cancer: results from study AB12003, Journal of Urology: September 2021-Volume 206-Issue Supplement 3. doi: 10.1097/JU.0000000000002149.11

[2] American Cancer Society. Cancer Facts & Figures 2023. Atlanta: American Cancer Society; 2023. Accessed June 2023. View Source

About study AB12003 Study

AB12003 was a prospective, placebo controlled, double blind, randomized, phase 3 trial, evaluating masitinib (6.0 mg/kg/d) in combination with docetaxel (IV 75 mg/m² plus prednisone for up to 10 cycles) as a first-line treatment of metastatic castrate resistant prostate cancer (mCRPC). Eligible patients were chemo-naïve with confirmed mCRCP, who had progressed on previous abiraterone treatment or were indicated for docetaxel treatment, and had a ECOG ≤1. Primary analysis was performed on a pre-specified targeted subgroup, defined as patients with baseline alkaline phosphatase levels (ALP) ≤250 IU/L, and on the overall population. Primary endpoint was progression free survival (PFS) (PCWG2 definition). The study was successful if improvement in median PFS relative to control reached a 3.9% level of significance for the target subgroup (alpha split with fallback procedure to conserve overall type-I error at 5% for the overall study cohort). Primary analysis was based on 450 patients in the targeted subgroup (ALP ≤ 250 IU/L). There was a total of 712 patients in the overall study cohort.

About masitinib

Masitinib is a orally administered tyrosine kinase inhibitor that targets mast cells and macrophages, important cells for immunity, through inhibiting a limited number of kinases. Based on its unique mechanism of action, masitinib can bedeveloped in a large number of conditions in oncology, in inflammatory diseases, and in certain diseases of the central nervous system. In oncology due to its immunotherapy effect, masitinib can have an effect on survival, alone or in combination with chemotherapy. Through its activity on mast cells and microglia and consequently the inhibition of the activation of the inflammatory process, masitinib can have an effect on the symptoms associated with some inflammatory and central nervous system diseases and the degeneration of these diseases.