Date: 2013-10-09
Type of information: Milestone
Compound: Tasquinimod TASQ
Company: Active Biotech (Sweden) Ipsen (France)
Therapeutic area: Cancer - Oncology
Type agreement: co-development
commercialisation
Action mechanism: immunomodulator/immunotherapy product. TASQ (tasquinimod, ABR-215050) binds to a molecule called S100A9 which is expressed in the white blood cells involved in the regulation of immune responses. S100A9 interacts with two known pro-inflammatory receptors (Toll like receptor 4 (TLR4) and receptor of advanced glycation end products (RAGE)) and this interaction is inhibited by TASQ (Björk et al PLoS Biology, April 2009).
Disease: prostate cancer
Details: * On April 18, 2011, Active Biotech AB and Ipsen have entered into a broad partnership to co-develop and commercialize Active Biotech's investigational compound Tasquinimod "TASQ". A global Phase III trial of TASQ in men with metastatic castrate-resistant prostate cancer (CRPC) was recently initiated by Active Biotech and patient recruitment is ongoing. This new partnership will broaden the scope of Ipsen’s uro-oncology franchise. Under the terms of the agreement, Active Biotech granted Ipsen exclusive rights to commercialize TASQ worldwide, except for North and South America and Japan where Active Biotech retains all commercial and marketing rights. Both companies will co-develop TASQ for the treatment of castrate-resistant prostate cancer, with the possibility to develop TASQ in other cancer indications. The development of TASQ is currently focused on the treatment of prostate cancer. TASQ is an antiangiogenic compound, meaning that it cuts off the supply of nutrients to the tumor. Up-regulation of thrombospondin-1 (TSP1) has been identified as one important component in order to understand and explain the anti-angiogenic mechanism of TASQ treatment of prostate cancer (Olsson et al, Mol Cancer May 2010).
The previously concluded clinical trial was a 2:1 randomized, placebo controlled, double-blind Phase II trial investigating up to 1 mg/day of TASQ versus placebo in 206 asymptomatic patients with metastatic castrate resistant prostate cancer (CRPC). The primary endpoint, patients with disease progression at six months, was reached. The results showed that the fraction of patients with disease progression during the six-month period was 31% for patients treated with TASQ compared with 66% for placebo-treated patients. The median progression-free survival was 7.6 months for the TASQ group, compared to 3.3 months for the placebo group (p=0.0042). TASQ treatment also had an effect on biomarkers relevant for prostate cancer progression and was generally well tolerated.
The ongoing clinical trial (funded by Active Biotech) is a global, randomized, double-blind, placebo-controlled Phase III trial in patients with metastatic CRPC. The aim of the study is to confirm TASQ's effect on the disease, with radiological progression-free survival (PFS) as the primary endpoint and overall survival as the secondary endpoint. The study will include about 1,200 patients in more than 250 clinics (www.clinicaltrials.gov).
Financial terms: Active Biotech is responsible for conducting and funding the Phase III pivotal clinical trial and will receive up to €200 million consisting of an upfront payment of €25 million and additional payments contingent upon achievement of clinical, regulatory and commercial milestones. In addition, Ipsen will pay Active Biotech progressive double-digit royalties on its net sales and will conduct and fund a European supportive study in prostate cancer patients out of its R&D budget. Eventual costs to develop TASQ in future other cancer indications will be shared.
Latest news: * On April 16, 2015, Active Biotech and Ipsen announced top line results of the 10TASQ10 study. While the study showed that tasquinimod reduced the risk of radiographic cancer progression or death compared to placebo (rPFS, HR=0.69, CI 95%: 0.60 – 0.80) in patients with metastatic castration resistant prostate cancer (mCRPC) who have not received chemotherapy, tasquinimod did not extend overall survival (OS, HR=1.09, CI 95%: 0.94 – 1.28). Efficacy results together with preliminary safety data do not support positive benefit risk balance in this population. Therefore the companies have decided to discontinue all studies in prostate cancer. Full results will be presented at an upcoming scientific conference. * On October 9, 2013, Active Biotech has announced that the company, under the terms of the co-development and commercialization agreement on tasquinimod, has received a milestone payment of 12 million euros from Ipsen. Today the development of tasquinimod is principally focused on the treatment of prostate cancer, but clinical studies in other cancer indications are performed. The ongoing 10TASQ10 trial met its enrollment target in December 2012 with 1,245 randomized patients as planned in the clinical protocol. The study recruited patients in 37 countries covering more than 200 centers. Active Biotech and Ipsen plan to conduct the primary PFS analysis for the 10TASQ10 trial in 2014, at the same time as the first interim overall survival (OS) analysis.
