AB Science patent for masitinib in the treatment of metastatic castrate resistant prostate cancer formally granted in the United States with a protection until 2042

US Patent Granted for Masitinib in Metastatic Prostate Cancer

AB Science announced that the United States Patent Office has formally granted a patent for its lead compound, masitinib, for methods of treating metastatic castrate resistant prostate cancer (mCRPC). This new US patent (US 12,648,944) ensures intellectual property protection for masitinib until May 2042, adding to the coverage already granted in Europe. Masitinib, in combination with docetaxel, has demonstrated positive progression-free survival (PFS) data in mCRPC patients, particularly those with low metastatic involvement, addressing a significant unmet medical need in a disease area that has seen limited new drug registrations in decades.

• The United States Patent Office has formally granted AB Science a patent (US 12,648,944) for masitinib in the treatment of metastatic castrate resistant prostate cancer (mCRPC). This patent provides intellectual property protection for masitinib in the US until May 2042, complementing existing IP coverage already granted in Europe (EP4175639) and with counterpart applications filed in other major international markets.
• Masitinib, when combined with docetaxel, demonstrated a significant progression-free survival (PFS) benefit in mCRPC patients with baseline alkaline phosphatase (ALP) levels ≤ 250 IU/L, as shown in study AB12003. This subgroup experienced a 21% reduction in the risk of progression (hazard ratio of 0.79 [0.64,0.97], p=0.0087). A more pronounced effect was observed in patients with ALP ≤ 100 IU/L, showing a 47% reduced risk of progression (hazard ratio=0.53, p=0.002).
• Metastatic castrate resistant prostate cancer represents a substantial unmet medical need, with a 5-year survival rate of approximately 32%. Despite being the world’s second most frequent cancer, there has been a lack of new registered drugs or combinations improving PFS or OS in this setting for the last 20 years. Masitinib's positive data in combination with docetaxel offers a potential new therapeutic option for this challenging patient population, which includes approximately 50,000 patients in the EU and 70,000 in the USA eligible for chemotherapy.

Masitinib's Targeted Approach for mCRPC with Low Metastatic Involvement

Across its clinical development program, masitinib has employed disease-specific patient selection strategies rather than molecular biomarkers per se, with enrichment criteria tailored to identify populations most likely to respond based on clinical phenotype, symptom severity, or disease trajectory. In the ALS trial (2021), a prospectively defined two-tiered stratification design was implemented using the ALSFRS-R progression rate from disease onset to baseline (ΔFS), partitioning patients into a primary efficacy population of "Normal Progressors" (ΔFS < 1.1 points/month) and a broader "Normal and Fast Progressor" cohort. This design successfully identified a more homogeneous, treatment-responsive subgroup: masitinib 4.5 mg/kg/day demonstrated a statistically significant between-group difference in ΔALSFRS-R of 3.4 points (95% CI 0.65–6.13; p=0.016), corresponding to a 27% slowing in the rate of functional decline among Normal Progressors, while no significant treatment effect was observed in the broader population or in either low-dose cohort.

In progressive multiple sclerosis (2022), patient selection focused on disease subtype and clinical activity status, enrolling adults aged 18–75 years with primary progressive MS (PPMS) or nonactive secondary progressive MS (nSPMS) — defined as absence of relapse for ≥2 years — with a baseline EDSS of 2.0–6.0, irrespective of time from onset. This design deliberately targeted a progressing but clinically non-inflammatory population, aligning with masitinib's proposed mechanism through mast cell and microglia modulation. In systemic mastocytosis (2018), enrollment was restricted to severely symptomatic adults aged 18–75 years with indolent or smouldering disease per WHO classification who were unresponsive to optimal symptomatic treatments; patients with cutaneous or non-severe systemic mastocytosis were excluded following a protocol amendment. Randomization was stratified by severe symptom type, with eligibility requiring at least one qualifying severe symptom: pruritus score ≥9, ≥8 flushes per week, Hamilton Rating Scale for Depression ≥19, or Fatigue Impact Scale ≥75.

In Alzheimer's disease (2023), selection criteria centered on disease severity stage, enrolling patients aged ≥50 years with a clinical diagnosis of mild-to-moderate probable AD and a Mini-Mental State Examination (MMSE) score of 12–25. This score-based stratification ensured enrollment of a cognitively impaired but not end-stage population, a window in which disease-modifying intervention may be most tractable. Masitinib 4.5 mg/kg/day demonstrated significant benefit over placebo on both the ADAS-cog (between-group difference −2.15; 97.5% CI −3.48 to −0.81; p<0.001) and ADCS-ADL (between-group difference 1.82; 97.5% CI −0.15 to 3.79; p=0.038), while the uptitrated 6.0 mg/kg/day arm yielded inconclusive results. Collectively, these trials reflect a consistent strategic principle: rather than genomic or proteomic biomarker selection, masitinib's development program has relied on clinical enrichment — through functional trajectory, symptom burden, disease subtype, and severity staging — to define populations where its mechanism of action is most likely to yield measurable benefit.

Why New Options Are Crucial for Metastatic Castrate Resistant Prostate Cancer

Metastatic castration-resistant prostate cancer (mCRPC) remains a significant clinical challenge, with no currently available treatment options capable of halting disease progression in the long term. Despite a rapidly expanding therapeutic armamentarium, outcomes remain poor, and the precise sequencing and selection of therapies continues to rely on incomplete evidence. The molecular complexity of the disease—compounded by tumor heterogeneity and incompletely understood resistance mechanisms—underscores the urgent need for more effective, personalized approaches.

• Inevitable progression under androgen deprivation therapy (ADT): Most patients develop CRPC within 1–2 years of ADT-induced remission, as adrenal glands and prostate cancer tissue continue to produce androgens despite castrate testosterone levels, sustaining tumor growth.

• Short-lived and ultimately insufficient survival benefits: Agents such as docetaxel and enzalutamide extend survival in mCRPC, but only transiently; patients invariably develop primary or secondary resistance, leading to disease progression or biochemical relapse.

• Poorly characterized resistance mechanisms: Prostate cancer progression is frequently driven by aberrantly activated kinase signalling pathways, acquired androgen receptor (AR) mutations or splice variants, and cancer stem cells—which, despite their small numbers, are primary drivers of metastasis, drug resistance, and recurrence.

• Heterogeneous treatment outcomes and lack of validated prognostic biomarkers: Significant tumor heterogeneity produces highly variable responses across patients, and the limitations of biomarker-unselected treatment approaches are increasingly apparent, highlighting the need for robust prognostic tools to identify patients at highest risk of poor outcomes.

• Complexity of treatment selection and sequencing: The optimal use of PARP inhibitors, PSMA-targeted radioligand therapy (RLT), and androgen receptor pathway inhibitors (ARPIs) requires individualized strategies informed by molecular profiling, functional imaging, prior treatment exposure, and safety considerations—an area where clinical guidance remains incomplete.

• Tolerability and patient-level variability: Comorbidities, organ function, disease burden, and adverse event profiles critically influence treatment selection, and agents such as dasatinib have demonstrated that limited anti-tumor activity combined with poor tolerability—with 43% of patients discontinuing due to toxicity—can render otherwise mechanistically rational approaches clinically impractical.

• Persistent mortality despite therapeutic advances: Although second-generation hormonal therapies have improved overall survival, the majority of men with metastatic prostate cancer develop progressive disease and ultimately succumb, reflecting the continued lethality of mCRPC in the absence of truly disease-modifying interventions.

Key Efficacy and Safety Outcomes from Masitinib's AB12003 Study

The CheckMate 7DX trial (NCT04100018), a double-blind, randomized phase 3 study enrolling 1,030 ARPI-pretreated, chemotherapy-naïve mCRPC patients across 27 countries, evaluated nivolumab (360 mg) plus docetaxel (75 mg/m²) every three weeks versus placebo plus docetaxel. Despite the immunotherapy rationale, the combination failed to demonstrate meaningful clinical benefit: median radiographic progression-free survival (rPFS) was 9.4 months versus 8.7 months (HR 0.96; 99% CI 0.77–1.19; p=0.59), and median overall survival (OS) was 18.7 versus 18.9 months (HR 1.09; 99.41% CI 0.84–1.43; p=0.36). From a safety standpoint, grade 3–4 treatment-related adverse events occurred in 44% of patients receiving nivolumab plus docetaxel versus 37% with placebo plus docetaxel, with neutropenia and decreased neutrophil count among the most common grade 3–4 events. Any-grade serious adverse events were reported in 21% versus 15%, and 12 deaths were attributed to the combination arm, including events of sepsis, myocarditis, pneumonitis, and Guillain-Barré syndrome.

The OMAHA-003 and OMAHA-004 trials (NCT06136624 and NCT06136650) represent randomized phase III investigations of opevesostat, a steroidogenesis inhibitor, versus an androgen receptor pathway inhibitor (ARPI) switch in previously treated mCRPC. The scientific rationale centers on acquired resistance to ARPIs mediated by AR ligand-binding domain mutations, which can enable promiscuous activation by non-androgen steroid hormones — a mechanism that steroidogenesis inhibition is designed to circumvent. Results from these trials are pending, but their design reflects a meaningful strategic shift toward targeting upstream steroid biosynthesis as a resistance-agnostic approach.

A network meta-analysis of olaparib (2026), incorporating nine studies from seven clinical trials and 2,355 patients, provided important biomarker-stratified insights into PARP inhibitor positioning in mCRPC. In patients with BRCA-mutated disease, olaparib combined with abiraterone demonstrated significant improvements in both PFS (HR = 0.61; 95% CrI 0.41–0.91) and OS (HR = 0.41; 95% CrI 0.21–0.80), with advantages observed consistently across PSA subgroups. However, for patients with BRCA wild-type, homologous recombination repair-mutated mCRPC, combination regimens did not yield significant incremental benefit over olaparib monotherapy, supporting single-agent use in that population. A complementary cabazitaxel network meta-analysis (2025), synthesizing 13 randomized controlled studies involving 5,814 patients, found that cabazitaxel at 25 mg/m² significantly improved OS and PFS relative to ARPIs and mitoxantrone, but was inferior to [¹⁷⁷Lu]Lu-PSMA-617 and TDM-cabazitaxel combinations on both endpoints. Notably, cabazitaxel combined with carboplatin was associated with a significantly higher rate of serious adverse events (RR 3.10; 95% CI 1.70–5.90) compared to cabazitaxel monotherapy, underscoring the toxicity cost of platinum-based augmentation.

Masitinib's Patent Fortifies Position in mCRPC

The recent granting of a US patent for masitinib, extending its intellectual property protection until 2042, marks a significant milestone for AB Science, particularly in the challenging landscape of metastatic castrate resistant prostate cancer (mCRPC). This extended exclusivity provides a crucial foundation for the drug's long-term commercial viability and strategic positioning.

Masitinib, a tyrosine kinase inhibitor (TKI), has demonstrated promising progression-free survival (PFS) data when combined with docetaxel in mCRPC patients, especially those with low metastatic involvement. This finding is particularly relevant given that mCRPC has historically been an area with limited therapeutic options, with docetaxel serving as a long-standing standard. While the treatment paradigm for mCRPC has seen some recent advancements with new FDA-approved agents and others in late-stage development, a significant unmet medical need persists, particularly for specific patient subsets.

However, several considerations are paramount as masitinib progresses:

• The efficacy data, specifically highlighted for patients with 'low metastatic involvement,' suggests that masitinib's clinical utility might be confined to a narrower patient population within the broader mCRPC spectrum. This specificity, while addressing a niche, could limit its overall market penetration.

• The evolving competitive landscape in mCRPC, with new agents entering the market and a robust pipeline of therapies, means masitinib will need to clearly differentiate itself and demonstrate compelling benefits to secure a strong foothold.

• Furthermore, as a TKI, masitinib is expected to carry a class-specific toxicity profile, including potential adverse events such as hypertension, skin reactions, diarrhea, and fatigue, which are common with other TKIs. Effective management of these side effects will be crucial for patient tolerability and adherence, influencing its real-world adoption.

Ultimately, this patent grant provides AB Science with a valuable asset and a clear path forward. The success of masitinib will hinge on its ability to demonstrate a favorable benefit-risk profile in its target population, navigate a dynamic competitive environment, and effectively manage the inherent challenges associated with TKI therapies. Its potential to offer a new, long-protected option for a specific mCRPC patient group could represent a meaningful step forward in this difficult-to-treat cancer.