Rare diseases remain untreatable globally despite significant advances in research enabling an understanding of their molecular basis and legislation providing regulatory and economic incentives to accelerate their development . Rare diseases lack treatment options and are often decades behind in research and development. A key factor in addressing this translational gap is applying advances in knowledge about rare diseases to potential medicines such as small molecules, monoclonal antibodies, protein replacement therapies, oligonucleotides, gene and cell therapies, and pharmaceuticals. It’s about choosing the best treatment for conversion. Diversion. Merck, a global pharmaceutical company, is working to develop a cure for one such rare disease, multiple sclerosis (MS). Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system prevalent in the Asia-Pacific region. It is the most common nontraumatic disabling neurological disorder in young adults. Like many other rare diseases, MS has received little attention from drug developers due to the small market opportunity for this patient group. Exchange with BioSpectrum Asia Liz Henderson, Senior Vice President APAC, Merck Healthcare describes the therapeutic prospects for this rare disease.
Why is multiple sclerosis (MS) worthy of attention and investment in APAC to develop new treatments?
In my opinion, there can never be too many treatment options for someone with a serious autoimmune disease like MS.
Merck believes that a healthier future requires significant investment. In 2018, our Healthcare business spent approximately 20% of total revenue on research and development activities aimed at discovering and developing new therapeutics. All of this is integrated into his four highly connected hubs strategically located on three continents: Darmstadt, Boston, Beijing and Tokyo.
What are Merck’s latest developments and investments in MS?
Merck has a long history in multiple sclerosis. We have been developing drugs to treat this disease for over 20 years and continue to invest heavily in this area of unmet need. A major goal of drug development programs for MS patients is to improve quality of life and slow disease progression. The goal is to reduce the burden of treatment, improve adherence, improve outcomes of care and facilitate management. It also encourages discussion within the MS community.
In 2017, we received EMA approval for Mavenclad, an oral therapy for the treatment of relapsing multiple sclerosis. Following this, the FDA approved the treatment in 2019. His first product to receive approval was his Rebif 20 years ago, an active neurology and immunology pipeline in lupus and multiple sclerosis with assets in stages 2 and 3 of development. I have.
In addition, we partner with companies with interesting new drug candidates that offer strategic additions to our portfolio. The recent acquisition of Chord Therapeutics will allow us to explore the potential of cladribine beyond MS in the indications of generalized myasthenia gravis (gMG) and neuromyelitis optica spectrum disorder (NMOSD). We primarily focus on molecules we know well and strive to maximize their potential for the benefit of our patients.
Additionally, a previous initiative called the Multiple Sclerosis Innovation Grant (GMSI) supports scientific and medical research advances in the field of MS. An early-stage research project will be funded to enable talented and inspiring researchers to better understand how to predict, diagnose, treat and monitor the progression of this disabling disease. .
How do you foresee the opportunities and challenges in the multiple sclerosis therapeutic area?
MS is a complex disease that is difficult to treat. The biggest challenge is the medical community’s understanding of the disease itself. Clinical trials are difficult because MS symptoms vary from patient to patient and responses to treatment vary widely.
Therefore, biomarker research will open up many possibilities in terms of treatment and response rates. Significant progress has been made in the identification of MS biomarkers over the past decade, allowing patients to be diagnosed more quickly and ensuring safe and personalized treatment.
Are there new pathways that could modulate the immune system in a more targeted manner than traditional immunosuppressive therapies to tackle rare diseases?
For immune-mediated diseases, the focus is on targeting the innate and adaptive components of the immune system. This means developing products aimed not only at inhibiting inappropriate immune activation that contributes to disease, but also increasing immune tolerance and training the body not to do so. Respond to specific triggers.
The immune system has many complex pathways that can go wrong. Therefore, numerous drugs have been developed by pharmaceutical companies that target various complex pathways involved in immune dysfunction.Disease-modifying therapies for patients with autoimmune diseases have evolved significantly. Drug discovery usually begins with identifying a specific target, such as blocking the Bruton’s Tyrosine Kinase (BTK) receptor. Evobrutinib, his BTK inhibitor developed by Merck, is currently in Phase 3 trials for MS.
From a mechanistic point of view, what excites me about this drug is that it is the first to show reduced levels of a key biomarker called circulating neurofilament light chain (NfL) levels that indicate neuronal damage and inflammation in MS patients. Being the only BTK inhibitor. Measurement of this biomarker can capture the extent of nerve axonal damage, especially early in the disease.
Monoclonal antibodies are considered the mainstay of treatment for MS because they can bind very specifically to large proteins called antigens and mediate their effects on specific pathways, whereas BTK inhibitors are much smaller molecules. Yes, and can enter the central nervous system. is a property not found in monoclonal antibodies and thus may influence disease evolution over time.
What drugs are in the immune-mediated rare disease pipeline? What are Merck’s development plans for 2023?
Collaborate with Global Business Development to seek out and evaluate external opportunities in immunology, including technology, preclinical and early clinical assets. In January 2022, we entered into licensing agreements with New York-based Trial Spark and High Line Bio for the drug spryfermin. Spryfermin is a disease-modifying treatment for osteoarthritis (OA) that improves cartilage thickness. This drug is a recombinant form of human fibroblast growth factor 18 and may be the first disease-modifying therapy for OA patients.
Across our neurology and immunology portfolios, we are also developing drugs to treat lupus, another autoimmune disease that occurs when the body attacks its own cells. Enpatoran is a novel, investigational immune checkpoint inhibitor being developed for two different types of lupus, systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE).
Lupus is a multifactorial autoimmune disease that impairs a variety of processes and cell types, including loss of tolerance to self-nuclear antigens, and is caused by overactivation of Toll Like Receptors (TLR) 7/8. TLR is a relatively new discovery (1985). They are an important part of our innate immune system, protecting us from pathogens. Inhibiting the overactivation of these proteins has recently been identified as a potential target for lupus.
Enpatoran is currently in Phase 2 trials with preliminary data expected to be generated soon.
In Neurology and Immunology, the company remains committed to multiple sclerosis with two approved therapies and is focused on the ongoing Phase 3 trial of evobrutinib, which is expected to be completed by the end of 2023.