Multiple sclerosis (MS) is a condition that can affect the brain and spinal cord, causing a wide range of potential symptoms, including problems with vision, arm or leg movement, sensation, or balance. It is a chronic autoimmune inflammatory disease of the central nervous system that damage and scars the sheath, and potentially the underlying nerves. Multiple sclerosis is affecting 2.3 million people worldwide, with females more affected than males.

According to the National Institute for Neurological Disorders and Stroke (NINDS), approximately, 250,000-350,000 people are suffering from the Multiple Sclerosis in the United States. The majority of the people with multiple sclerosis are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. The most common symptoms associated with MS include fatigue, difficulty walking, vision problems, problems controlling the bladder, etc. The average life expectancy is slightly reduced for people with MS. The progress, severity, and specific symptoms of MS in any one person cannot yet be predicted.

There are various diversify companies involved in the discovery and development of a potentially robust clinical pipeline for the treatment of Multiple Sclerosis. Merck Healthcare KGaA, Novartis, Sanofi, TG Therapeutic, Biogen, MedDay Pharmaceuticals SA, and Hoffmann-La Roche are the major market players

Actelion (Ponesimod)

Ponesimod is an investigational selective sphingosine-1-phosphate receptor 1 (S1P1) modulator that inhibits S1P protein activity and reduce the number of circulating lymphocytes that can cross the blood-brain barrier. The Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen) had submitted the New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ponesimod for the treatment of adult patients with relapsing multiple sclerosis (MS).

Merck Healthcare KGaA (Evobrutinib)

Evobrutinib is an investigational oral inhibitor of Bruton’s tyrosine kinase (BTK) which is thought to be important in the development and functioning of various immune cells including B lymphocytes and macrophages. Currently, clinical research study is ongoing on Evobrutinib. The study would evaluate the efficacy and safety of evobrutinib administered orally twice daily versus Teriflunomide (Aubagio), administered orally once daily in participants with Relapsing Multiple Sclerosis (RMS).

Hoffmann-La Roche (Ocrelizumab)

Ocrelizumab is a humanized monoclonal antibody that selectively targets the CD20-positive B-cells implicated in the inflammatory and neurodegenerative processes of multiple sclerosis (MS), to effectively impact disease progression while maintaining immunosurveillance.

A clinical trial of Phase-III study is being conducted to treat MS. This is a single arm, open label, multicenter extension study in participants on ocrelizumab therapy at the end of Treatment period of the Roche P-trial. Participants would receive the treatment with ocrelizumab as single 600 mg infusions every 24 weeks for two years.

TG Therapeutics, Inc. (Ublituximab)

Ublituximab (TG-1101) is a monoclonal antibody that targets CD20 positive B-cells, a component of the body’s immune system. When it attaches to the B-cell it triggers immune reactions (including antibody-dependent cellular cytotoxicity, ADCC, and antibody-dependent cellular phagocytosis that result in the death of the targeted B-cell).

While ublituximab is a novel patented molecule, it’s mechanism of action is similar to the approved anti-CD20 monoclonal antibodies. Ublituximab has been bioengineered to remove certain sugar molecules from the anti-CD20 antibody, which are naturally occurring. The removal of the sugar molecules in a process called glycoengineering have enhanced the potency of ublituximab with data showing 50-100x greater activity than non-bioengineered anti-CD20 antibodies.

MedDay Pharmaceuticals SA (MD1003)

MD1003 is a highly concentrated oral formulation of biotin currently under clinical investigation as a treatment for primary and secondary progressive multiple sclerosis (PPMS and SPMS). It is being developed by MedDay. It is a promising treatment that exhibits the pro-myelinogenic effects and enhances the supply of energy for nerve impulse transmission.

Biogen (Opicinumab)

Opicinumab is a human monoclonal antibody that targets LINGO-1, a protein that suppresses the redevelopment of axons (brain cells that send functional information throughout the body) and re-formation of myelin sheaths (fibers that protect the axons). Axons and myelin sheaths are lost or damaged in patients with MS, leading to loss of physical and cognitive function. By blocking LINGO-1, opicinumab is formulated to promote regeneration of axons and myelin.

The Phase II, double-blind AFFINITY study is assessing the effectiveness of opicinumab as an add-on therapy in people with relapsing or secondary-progressive forms of MS (RMS or SPMS).

Novartis (Ofatumumab)

Ofatumumab is a fully human anti-CD20 monoclonal antibody (mAb) self-administered by a once-monthly subcutaneous injection in development for RMS. Ofatumumab works by binding to the CD20 molecule on the B-cell surface, distinct from that of other anti-CD20 antibodies, and induces potent B-cell lysis and depletion. The selective mechanism of action and subcutaneous administration of ofatumumab allows precise delivery to the lymph nodes, where B-cell depletion in MS is needed, while sparing those in the spleen that help maintain protective immunity. Once-monthly dosing of ofatumumab also allows faster repletion of B-cells, and offers more flexibility as no first dose observations or laboratory monitoring is required. Novartis obtained rights for ofatumumab from Genmab in all indications, including MS, in December 2015.

Novartis (BAF312)

Siponimod is an investigational, selective modulator of specific subtypes of the sphingosine-1-phosphate (S1P) receptor. Siponimod binds to the S1P1 sub-receptor on lymphocytes, which prevents them from entering the central nervous system (CNS) of patients with multiple sclerosis. This leads to the anti-inflammatory effects of siponimod. Siponimod also enters the CNS and binds to the S1P5 sub-receptor on specific cells in the CNS (oligodendrocytes and astrocytes). By binding to these specific receptors, siponimod has the potential to modulate damaging cell activity, and preclinical studies suggest that it may prevent synaptic neurodegeneration and promote remyelination in the central nervous system.

Sanofi (Teriflunomide)

Teriflunomide is the first original ‘once-daily’ oral ‘disease modifying therapy’ (DMT) for Multiple Sclerosis. It offers an effective, safe and a convenient option that is indicated as a first-line treatment for relapsing forms of Multiple Sclerosis that must be taken once a day, with or without food.

Emerging Pipeline Landscape of Multiple Sclerosis (MS)

Company name	Product Name	Stage of development	Route of administration	Mechanism of action
Merck Healthcare KGaA	Evobrutinib + Teriflunomide	Phase III	Oral	BTK inhibtor
Actelion	Ponesimod	Phase III	Oral	S1P1 immunomodulator
Novartis	BAF312 (Mayzent™)	Phase III	Oral	S1P1 Modulator
Novartis	Ofatumumab	Phase III	Subcutaneous	anti-CD20
MedDay Pharmaceuticals	MD1003	Phase III	Oral	Enzyme modulators
F. Hoffmann-La Roche AG	Ocrelizumab/ RG1594	Phase III	Intavenous	anti- CD20 positive B- cells
Sanofi	Teriflunomide	Phase III	Oral	Dihydroorotate dehydrogenase inhibitors
Sanofi	Alemtuzumab	Phase III	Intravenous	dihydro-orotate dehydrogenase inhibitor
TG Therapeutics	Ublituximab	Phase III	Oral	anti- CD20
Biogen	Opicinumab	Phase II	Intravenous	anti-LINGO

Novel Coronavirus: Recent Updates

Sanofi and GSK Collaborate to Develop Vaccine for COVID-19

Sanofi and GlaxoSmithKline have signed a letter of intent to develop an adjuvanted vaccine for COVID-19, using innovative technology. Sanofi would contribute its S-protein COVID-19 antigen, which is based on recombinant DNA technology whereas the GSK would contribute its pandemic adjuvant technology. The use of an adjuvant technology would help in reducing the amount of vaccine protein required per dose, allowing more vaccine doses to be produced and therefore help in protecting the more people.

China Approves Two Experimental Coronavirus Vaccines to enter Clinical Trials

China has approved early-stage human tests for two experimental vaccines to combat the new coronavirus. One vaccine is being developed by a Beijing-based unit of Nasdaq-listed Sinovac Biotech, and another vaccine is being developed by the Wuhan Institute of Biological Products.

AstraZeneca to Test the Impact of Cancer Drug Calquence on Coronavirus Patients

AstraZeneca is planning to start a clinical trial of its cancer drug i.e. Calquence to assess its potential to control the exaggerated immune system response associated with COVID-19 infection in severely ill patients.

Calquence (acalabrutinib) belongs to a class of drugs called Bruton’s tyrosine kinase (BTK) inhibitors which can suppress autoimmune diseases. Calquence is currently used to treat certain types of blood cancers, has already been approved for the treatment of adult patients with chronic lymphocytic leukaemia in the United States and several other countries.

Celltrion Identifies Antibody Candidates against COVID-19

Celltrion has successfully selected the most potent antibody candidates to neutralise SARS-CoV-2, the virus causing COVID-19. Celltrion will begin cell-line development mass production of the selected therapeutic monoclonal antibody. The Company would conduct the efficacy and toxicity testing with Korea Centers for Disease Control and Prevention (KCDC) of the selected therapeutic monoclonal antibody in mice and non-human primates.

Immunomic collaborates with PharmaJet and EpiVax for COVID-19 Vaccine

Immunomic Therapeutics has entered into a collaboration with PharmaJet and EpiVax to develop a nucleic acid vaccine candidate against COVID-19. This collaboration would help in developing a vaccine that is scalable, heat-stable and easy to administer using PharmaJet’s Tropis needle-free injection system.

Vir selects Samsung Biologics to Produce COVID-19 Antibodies

Vir Biotechnology has selected South Korea-based Samsung Biologics for large-scale production of antibodies to potentially treat Covid-19. Under the terms of the collaboration, Samsung Biologics would provide the manufacturing services for Vir’s monoclonal antibody (mAb) programme targeting the novel coronavirus, SARS-CoV-2. Vir’s lead mAb candidates, VIR-7831 and VIR-7832, had showed high affinity for the spike protein of SARS-CoV-2 and ability

Eli Lilly to Begin Testing RA Drug Olumiant and an Anti-Ang2 Drug in COVID-19 Patients

Eli Lilly plans to explore the use of its rheumatoid arthritis drug i.e., Olumiant (oral JAK1/JAK2 inhibitor) as a treatment for hospitalized patients with COVID-19. Olumiant (Baricitinib) is approved in more than 65 countries as a treatment for adults with moderately to severely active rheumatoid arthritis. The clinical trial of Olumiant for COVID-19 would begin this month and results are expected within the next two months.

Moreover, the company is planning to advance LY3127804, an investigational selective monoclonal antibody against Angiopoietin 2 (Ang2), to Phase II testing in pneumonia patients hospitalized with COVID-19 who are at a higher risk of progressing to Acute Respiratory Distress Syndrome (ARDS). Ang2 is known to be elevated in ARDS patients and Lilly will test whether inhibiting the effects of Ang2 with a monoclonal antibody can reduce the progression to ARDS or the need for mechanical ventilation in COVID-19 patients

Promising Clinical Trial Results of Gilead Sciences’ Antiviral Drug Remdesivir for COVID-19

Gilead Sciences Inc.’s experimental drug i.e. remdesivir has shown the promise results in early analysis. All the patients received remdesivir for up to 10 days on a compassionate use basis. The clinical trial demonstrated the clinical improvement was observed in 36 of 53 patients (68%) over the 18 days with 17 of the 30 patients on mechanical ventilation being able to get off the breathing device. Almost half of the patients studied were ultimately discharged, while 13% died. Mortality was highest among those who were on a ventilator, with 18% of them dying. Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy

FDA Approves Rutgers’ Saliva Test for COVID-19

The diagnostic saliva test developed by RUCDR Infinite Biologics with Spectrum Solutions and Accurate Diagnostic Labs (ADL) has received the Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA). This test involves the use of the saliva for the diagnosis of the COVID-19.

This test has eliminated the need for collecting the sample through nasopharyngeal or oropharyngeal as the current COVID 19 diagnostic test requires a swab from deep in the nasal passages or the back of the throat. It puts the healthcare workers at risk of catching an infection. The diagnostic saliva test uses easy-to-collect saliva samples instead of the more difficult deep nose swabs in comparison to the existing diagnostic tests and would reduce the risk of healthcare workers from getting the infection.