Entrectinib for ROS1 fusion positive, locally advanced or metastatic non-small cell lung cancer
Entrectinib is a drug that specifically targets and blocks the ROS1 protein overproduced in many types of cancers including NSCLC. Preclinical trials suggest it may be more potent in targeting ROS1 than the currently approved therapy crizotinib. If licenced entrectinib would provide an additional specific treatment option for patients with ROS rearranged, locally advanced or metastatic NSCLC.
Ivosidenib for acute myeloid leukaemia with IDH1 mutation
Ivosidenib belongs to a new class of therapies that works by inhibiting the mutated IDH1 enzyme, which in turn reduces the level of d-2-hydroxyglutarate (2-HG), an oncometabolite which impairs myeloid differentiation, increases proliferation of myeloblasts, and blocks cellular differentiation. There are currently no approved treatment options in the EU/UK for those who have relapsed or refractory AML with an IDH1 mutation. If licensed, ivosidenib could be an effective precision medicine for this patient group.
Givosiran for acute hepatic porphyria (AHP)
Givosiran is made of a short, synthetic strand of genetic material called ‘small interfering RNA’ (siRNA) that has been designed to interfere with the production of an enzyme involved in an early step in making haem. By blocking this early step of haem production in patients with AHP, givosiran is expected to prevent the next steps which produce substances that accumulate in the body and cause the symptoms of the disease.
Bempedoic acid (monotherapy) or bempedoic acid in combination with ezetimibe for primary hypercholesterolaemia or mixed dyslipidaemia
The current standard of care for patients with hypercholesterolaemia is primarily statins which are capable of reducing LDL-C. There is however a subset of patients who are unable to tolerate statins due to adverse effects. Bempedoic acid monotherapy or in combination with ezetimibe are once-daily tablets in development for patients unable to tolerate statins at all, or are not able to tolerate the necessary dose of statin required to reach their LDL-C goal, or are recommended not to use them due to various circumstances. Bempedoic acid and ezetimibe both act in complementary ways to lower LDL-C. These therapies may offer additional and effective treatment options to use in combination with dietary changes and other lipid-modifying therapies to treat primary hypercholesterolaemia or mixed dyslipidaemia.
Avelumab in combination with axitinib for advanced or metastatic renal cell carcinoma – first line
Avelumab is a human monoclonal antibody that works by inducing cancer cell death and restoring immune response against cancer cells. Axitinib works by blocking the growth of
blood vessels that supply the cancer cells. Their combined mechanism of actions may result in more effective cancer growth inhibition with manageable toxicity profiles. If licensed,
avelumab in combination with axitinib may offer an additional treatment option for people with advanced renal cell carcinoma that have not been treated previously.
Tagraxofusp for blastic plasmacytoid dendritic cell neoplasm
Tagraxofusp is a fusion protein formed by combining interleukin‐3 (IL‐3) and truncated diphtheria toxin (DT). It causes inactivation of protein synthesis, and death of the target cell.
Treatment for BPDCN has included therapies that are used for AML, acute lymphoblastic leukaemia (ALL), or lymphoma. If licensed, tagraxofusp will offer the first prospectively
studied treatment option for BPDCN for which there are limited treatment options and a significant unmet medical need.
Atezolizumab in combination with Nab-paclitaxel for unresectable, locally advanced or metastatic triple-negative breast cancer – first line
Atezolizumab combined with nab-paclitaxel is the first product to demonstrate positive phase III immunotherapy results in patients with locally advanced or metastatic TNBC who have not received prior systemic therapy. Atezolizumab is a monoclonal antibody that binds to the programmed cell death 1 ligand (PD-L1) and blocks its interaction with the programmed cell death protein 1 (PD-1), thereby enhancing T-cell activity against tumours. Nab-paclitaxel (paclitaxel formulated as albumin bound nanoparticles) is an anti-microtubule agent that inhibits cell growth by preventing mitosis. The combination may offer a first-line treatment option to improve clinical efficacy in the treatment of people with TNBC, an aggressive disease with no approved targeted therapy.