Among the most incredible achievements of humankind over the last few decades are the indisputable advancements in medical science — remarkable treatments that contribute to longer, healthier lives worldwide. Yet, despite awe-inspiring innovations, millions of people live with complicated, difficult-to-treat conditions for which there remain limited or no treatment options.
Alkermes is working to change this. As a rare company in the biopharmaceutical industry, Alkermes seeks to tackle some of the largest and most pressing public health challenges like addiction, serious mental illness and cancer. Its mission is to advance cutting-edge science and develop innovative medicines, while advocating for patients to help address complicated health challenges. This is what drives everyone at the company to keep striving to advance science on behalf of patients every day.
The company’s roots in drug formulation and delivery began with the goal of improving the pharmacology of existing drug molecules. Alkermes chose targets with potential to add significant value — aiming to develop medicines to address unmet needs for patients through formulation, prodrug and delivery technologies. Since then, Alkermes has evolved into a developer of novel medicines to tackle therapeutic challenges in both neuroscience and oncology. Its transformation is built on extensive technical capabilities in biology and chemistry, bolstered through innovation and strategic business development.
Innovating in neuroscience
Neuroscience has always been a core focus area for Alkermes. The company’s foundational expertise in patient-focused R&D efforts has led to an exploration of new ways to address persistent treatment gaps and develop potential best-in-class or first-in-class medicines based on known biology.
For example, many neurological disorders are characterized by aberrant synaptic pathology. For these disorders, targeting the synapse may slow progression and preserve cognitive and functional abilities. Studies show that inhibition of some histone deacetylases (HDAC), a family of enzymes found in the nucleus of cells, may increase the number of synapses or connections between neurons, which could have therapeutic value in certain neurological disorders.1,2 Alkermes’ HDAC inhibitor platform is designed to navigate historical challenges of hematological toxicities and suboptimal brain exposure by selectively engaging the multi-protein complexes associated with prosynaptic function. Alkermes has advanced its first investigational selective HDAC inhibitor candidate, ALKS 1140, into first-in-human studies and looks forward to evaluating it across neurodegenerative and neurological disorders.
Alkermes has also progressed its orexin 2 receptor agonist, ALKS 2680, which was recently nominated to advance toward the clinic. The biology of the orexin pathway has been validated in narcolepsy and Alkermes sees a compelling opportunity in this space. Preclinical data has been encouraging and the company looks forward to advancing this candidate into human studies to better understand its safety profile.
Impact and future directions in oncology
Alkermes’ evolution to oncology was guided by its unique protein-engineering capabilities and a desire to help patients with difficult-to-treat cancers who have limited treatment options. Leveraging its protein engineering expertise, Alkermes has sought to modify immune cytokines with validated anti-tumor functions, to elevate their therapeutic potential and applicability.
This approach led Alkermes to its first investigational immuno-oncology drug candidate, nemvaleukin alfa (nemvaleukin). Nemvaleukin is a redesigned novel cytokine that is designed to leverage the known anti-tumor effects of interleukin-2 (IL-2), while mitigating certain toxicity issues which have limited IL-2’s use.
While recombinant human IL-2 (rhIL-2) is an approved treatment for certain cancers, it binds to multiple types of IL-2 receptors (IL-2R), which is associated with a challenging therapeutic profile.3,4 The undesirable effects of rhIL-2 are believed to be primarily attributed to its ability to activate regulatory T cells (T regs) and vascular endothelial cells (VECs). The activation of T regs may dampen anti-tumor immune mechanisms, while the activation of VECs is associated with toxicities like vascular leakage.4,5 Nemvaleukin is selective for the intermediate-affinity IL-2R found on cancer-fighting CD8+ T cells and natural killer cells. This selectivity is designed to mitigate the unfavorable effects of IL-2, while potentially driving an expansion of the cancer-fighting immune cells.
Nemvaleukin is currently being studied both as a monotherapy and in combination with an approved immunotherapeutic agent, pembrolizumab. Alkermes is encouraged by the data seen to date in patients with high unmet needs, including those who progressed on previous treatment with checkpoint inhibitors (CPIs) as well as those who are not eligible for treatment with CPIs. Nemvaleukin is currently the only investigational IL-2 variant in development that has received FDA Fast Track Designations in two indications — as monotherapy in mucosal melanoma and in combination with pembrolizumab in platinum-resistant ovarian cancer (PROC), and an Orphan Drug Designation in mucosal melanoma. Alkermes recently initiated the ARTISTRY-7 phase 3 trial in PROC and looks forward to the data emerging from this potential registrational study.
Innovation at Alkermes is driven by three principles: great science, deep compassion, and real impact. The company pursues these goals in a collaborative, respectful and inclusive culture, inspired by a patient-focused mission that employees are passionate about. Learn more about the company’s recent advancements at Alkermes.com.
Craig Hopkinson, M.D. is Executive Vice President, Research & Development and Chief Medical Officer of Alkermes
- Morrison, J., Baxter, M. Nat Rev Neurosci. 2012
- Verstraelen, P et al. Front. Neurosci. 2018
- Wrangle JM et al. IL-2 and Beyond in Cancer Immunotherapy. J Interferon Cytokine Res. 2018 Feb 1; 38(2): 45–68. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815463/M/small>
- Jiang T et al. Role of IL-2 in cancer immunotherapy. Oncoimmunology. 2016 Jun; 5(6): e1163462. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4938354/
- Baluna R. and Vitetta ES. Vascular leak syndrome: a side effect of immunotherapy. Immunopharmacology. 1997 Oct;37(2-3):117-32. https://pubmed.ncbi.nlm.nih.gov/9403331/