Sickle Cell Disease (SCD) is a rare blood disorder that affects the hemoglobin involved in delivers oxygen to cells throughout the body. It is inherited in an autosomal recessive trait in which both copies of the genes present in each cell have mutations. The parents of an individual with an autosomal recessive condition comprised of one copy of the mutated gene, and do not show signs and symptoms of the condition. The atypical hemoglobin molecules called hemoglobin S are present among the patients. Sickle cell disease is characterized by the presence of sickle or crescent-shaped, red blood cells in the bloodstream. Sickle Cell Disease occurred due to the mutations in the hemoglobin beta (HBB) gene.
Sickle Cell Disease Epidemiology Insights
The United States accounts for the highest prevalent cases of Sickle cell disease followed by the EU5 countries (France, Germany, Spain, Italy, and the United States), and Japan
According to the Centers for Disease Control and Prevention (CDC), Sickle Cell Disease affects approximately 100,000 Americans
Sickle Cell Disease occurs among about 1 out of every 365 Black or African-American births
Sickle Cell Disease occurs among about 1 out of every 16,300 Hispanic-American births
Approximately, 1 in 13 Black or African-American babies is born with sickle cell trait (SCT).
The mutations in the HBB gene are common in people from African, Mediterranean, Middle Eastern, and Indian ancestry and in people from the Caribbean and parts of Central and South America, but can be found in people of any ethnicity
Vitiligo is a chronic disorder that causes areas of skin to lose color. When skin cells that make color are attacked and destroyed, the skin turns a milky-white color. Various factors such as autoimmune disease, genetic factors, & neurogenic factors lead to the development of Vitiligo. The main symptom associated with vitiligo is the loss of natural color. The patches can show up on any part of your body and can affect the skin, which gets milky-white patches, usually on the hands, feet, arms, and face, hair, which can turn white on the scalp, eyebrow, eyelash, and beard & the inside of your mouth or nose. People with vitiligo can also get problems with the eyes and ears. In addition, people with the disorder may worry about how their skin looks, which can affect general well-being.
Vitiligo is the most common skin depigmentation disorder with an average prevalence estimated to be between 0.5% to 2% of the global population. An estimated 65-95 million people of all ages, sexes, and ethnicities worldwide suffer from vitiligo, including approximately 2.4 million people in the United States. The majority (70–80%) of patients with vitiligo experience disease onset before age 30. Approximately 30% have childhood-onset vitiligo before age 12.
Currently, there are no FDA-approved therapies for vitiligo. Dermatologists typically prescribe topical corticosteroids, topical calcineurin inhibitors, and/or phototherapy for the treatment of vitiligo. Therefore, pharmaceutical companies such as Incyte Corporation, Dermavant Sciences GmbH, Aclaris Therapeutics, Inc. Amgen and other companies are developing novel therapies for the treatment of Vitiligo.
Incyte Corporation (Ruxolitinib/INCB018424)
Ruxolitinib is a Janus kinase (JAK1/JAK2) inhibitor discovered by Incyte scientists. Overactive signaling through the JAK-STAT pathway has been associated with many types of disease, including a group of rare blood cancers called myeloproliferative neoplasms (MPNs), as well also used for the treatment of Vitiligo. Ruxolitinib is currently under the clinical trial of Phase III. The purpose of this study is to evaluate the efficacy and safety of ruxolitinib cream in adolescent and adult participants with non-segmental vitiligo for whom total body involved vitiligo area (facial and nonfacial) does not exceed 10% body surface area (BSA).
Cerdulatinib is a dual inhibitor of the Janus kinase (JAK) and spleen tyrosine kinase (Syk) pathways, which Dermavant is evaluating as a differentiated topical treatment option for vitiligo and other inflammatory skin conditions such as atopic dermatitis. The Phase IIa study is a multi-center, randomized, double-blind, vehicle-controlled study to assess the safety, tolerability, and systemic exposure of cerdulatinib gel 0.37%, dosed twice daily for six weeks versus vehicle in 30 adult patients aged 18-70 years diagnosed with vitiligo. The primary endpoints of the study are the safety and tolerability of topical administration of cerdulatinib gel 0.37% in adult subjects with vitiligo assessed by frequency, duration, and severity of adverse events (local and systemic), vital signs, laboratory values, and local tolerability scale (LTS) scores.
Aclaris Therapeutics, Inc. (ATI-50002/ATI-502)
ATI-502 (AA-201 Topical), is an investigational topical Janus Kinase (JAK) 1/3 inhibitor, developed by aclaris therapeutics used to treat Vitiligo. Currently, ATI-502 is evaluated under the clinical trial study of Phase II. This is a multicenter, open-label study designed to evaluate the safety, tolerability, and efficacy of ATI-50002 Topical Solution 0.46% in subjects with non-segmental facial vitiligo. Subjects would be required to have a clinical diagnosis of non-segmental facial vitiligo affecting at least 0.25% of total body surface area (TBSA) (excluding upper and lower eyelids, mucosal lip areas, and forehead and chin areas covered by the stereotactic positioning device for photography) with at least one area of the face with normal pigmentation. Twenty-four eligible subjects would receive ATI-50002 Topical Solution, 0.46%, BID for 24 weeks.
PF-06651600 is an oral JAK3 inhibitor used to treat Vitiligo. The JAK pathways are believed to play an important role in inflammatory processes as they are involved in signaling for over 50 cytokines and growth factors, many of which drive immune-mediated conditions. JAK inhibition may offer patients with these conditions a potential new advanced treatment option. PF-06651600 initiated a Phase II clinical trial study. This is a randomized, double-blind, parallel-group, multicenter study with an extension period. The study would have a maximum duration of approximately 60 weeks. This includes an up to 4 weeks Screening Period, a 24-week dose-ranging period, an up to 24 week extension period and an 8 week Follow up Period.
Amgen (AMG 714)
AMG 714 (PRV-015) is a human immunoglobulin monoclonal antibody that binds to IL-15 developed by amgen used to treat Vitiligo. Currently, AMG 714 is evaluated under a clinical trial study. The Phase IIa, double-blind, placebo-controlled, multi-center, proof of concept trial of AMG 714 for the treatment of vitiligo. Participants would be randomized 2:1 to receive AMG 714 or placebo for AMG714. The random assignment would be stratified by active versus stable vitiligo.
Every year June 25 is celebrated as the World Vitiligo Day to raise awareness regarding Vitiligo, fight prejudice, and raise funds for research, support & education. The aim of this day is to include the recognition of the bullying, social neglect, psychological trauma, and disability of millions of people affected by vitiligo. The primary purpose of this day is to raise money for research, give free skin exams, and educate physicians on how to best take care of patients with vitiligo.
Vitiligo is the long term skin condition in which the skin loses the pigment i.e. melanin, essential for determining the color of skin, hair, and eyes. This leads to the slow growth of the white patches of irregular shapes on the skin. Vitiligo can also affect the mucous membranes, including tissues inside the mouth and nose. It can affect people of all skin types but is generally noticeable much in darker skin people.
Around 1 out of 10 people i.e. 1-2% of people are suffering from Vitiligo worldwide
The United States accounts for the highest prevalent cases of Vitiligo in comparison to the EU5 (Germany, France, Spain, Italy, and the United Kingdom) and Japan
Vitiligo is classified as the non-segmental, and segmental Vitiligo. Non-segmental Vitiligo is most prevalent in comparison to the segmental Vitiligo
Approximately, 95% of the people develop the condition prior to age 40.
Around 20% of people have a family member suffering from Vitiligo
Males and females are almost equally affected by Vitiligo
Vitiligo is sometimes associated with certain other medical conditions, including thyroid dysfunction, diabetes mellitus, Addison’s disease, etc.
Several factors such as autoimmune disease, genetic factors, sunburn or any cut, oxidative stress, neurochemicals, and exposure to the industrial chemicals increase the risk of developing Vitiligo
Myasthenia Gravis is a chronic autoimmune, neuromuscular disease that causes weakness in the skeletal muscles that worsens after periods of activity and improves after periods of rest. These muscles are responsible for functions involving breathing and moving parts of the body, including the arms and legs. It is characterized by muscular fatigue leading to extreme weakness. The fatigue is caused by the loss of ability to convert nerve impulses into muscle contraction. The disease affects muscles controlling voluntary movement including those associated with actions such as swallowing and breathing and usually begins in a mild form. Typical first symptoms are associated with the eyelid, sight, swallowing, and speech. Focal MG usually develops more or less rapidly into generalized MG with symptoms that appear in the arms and abdomen and subsequently in the legs and respiratory muscles.
Various diagnostic tests such as electro-diagnostics, diagnostic imaging, pulmonary function tests, and other tests are used for the diagnosis of Myasthenia Gravis. Thymectomy, Monoclonal antibody, Anticholinesterase medications, and Immunosuppressive drugs are recommended for the treatment of myasthenia gravis. Several pharmaceutical companies such as CuraVac, argenx BVBA, Cartesian Therapeutics, Momenta Pharmaceuticals, Inc., RemeGen, and others are involved in the development of novel therapies for the treatment of Myasthenia Gravis.
Myasterix (CV-MG01) is an investigational therapeutic vaccine being developed by Curavac to alleviate the symptoms of myasthenia gravis. Myasterix is likely to have fewer side effects and a simpler method of administration than other therapies. The Myasterix vaccine induces the body to produce a different type of antibody, which binds to autoantibodies and T-cell receptors associated with myasthenia gravis. Obstructing receptors of the anti-AChR T-cells with the Mysterix-produced antibody prevents autoimmune production of anti-AChR antibodies. This is expected to unblock the AChR, restoring neuromuscular communication via acetylcholine successfully binding to its receptor.
Myasterix, is currently investigated under a clinical trial study. The Study CV-0002 is the first clinical trial administering CV-MG01 in humans. This clinical trial is a safety and proof-of-concept study (proof of mechanism of action) intended to assess the safety, tolerability, and immunogenic response following three subcutaneous injections of CV-MG01 as a potential therapeutic vaccine / active immunotherapy in myasthenia gravis (MG) patients.
Argenx BVBA (ARGX-113/ Efgartigimod)
Efgartigimod is designed as a first-in-class investigational antibody fragment to target the neonatal Fc receptor (FcRn). Efgartigimod is being evaluated for the treatment of patients with severe autoimmune diseases with confirmed presence of pathogenic immunoglobulin G, IgG autoantibodies, where a severe unmet medical need exists.
Cartesian Therapeutics (Descartes-08)
Descartes-08 is a CD8+ CAR-T investigational therapy that targets cells expressing B-cell Maturation Antigen (BCMA), a protein expressed by all plasma cells. Descartes-08 is engineered to have a defined and predictable half-life, enabling repeat dosing to maximize potency while minimizing the risk of toxicity
UCB Biopharma S.P.R.L. (Rozanolixizumab)
Rozanolixizumab is a subcutaneously administered, humanized monoclonal antibody that specifically binds, with high affinity, to human FcRn. It has been designed to block the interaction of FcRn and IgG, inhibiting IgG recycling and inducing the removal of pathogenic IgG autoantibodies. Rozanolixizumab is under clinical development with the aim of improving the lives of people with pathogenic IgG-autoantibody-driven autoimmune diseases, including ITP, myasthenia gravis (MG) and chronic inflammatory demyelinating polyneuropathy (CIDP), by driving removal of pathogenic IgG autoantibodies
Momenta Pharmaceuticals, Inc.( M281/ Nipocalimab)
Nipocalimab (M281) is a fully human, anti-FcRn (neonatal Fc receptor), aglycosylated IgG1 monoclonal antibody. Nipocalimab (M281) has the potential of improving the clinical signs and symptoms of MG by blocking FcRn-mediated IgG recycling, thereby reducing pathogenic autoantibodies including the most common autoantibodies, anti-AChR and anti-MuSK. Nipocalimab, is investigated under clinical trial. The purpose of this study is to evaluate the safety, tolerability, and efficacy of M281 administered to participants with generalized myasthenia gravis (gMG) who have an insufficient clinical response to ongoing standard of care therapy.
Immunovant Sciences GmbH (IMVT-1401)
The investigational drug product candidate, IMVT-1401 (formerly known as RVT-1401), is a novel, fully human monoclonal antibody targeting the neonatal Fc receptor (FcRn). IMVT-1401 has the potential to address a variety of IgG-mediated autoimmune diseases as a subcutaneous injection. The FcRn receptor facilitates IgG recycling. IMVT-1401 enhances the degradation of IgG by targeting FcRn and preventing endogenous IgG from binding. This increased catabolism of IgG may curtail the harmful immune response exhibited by auto-antibodies.
Catalyst Pharmaceuticals, Inc. (Amifampridine Phosphate)
Amifampridine, a neuronal potassium channel blocker, is used for the treatment of MuSK-positive myasthenia gravis. Currently, Catalyst is enrolling patients into a phase III trial examining amifampridine for the treatment of Myasthenia Gravis. The MuSK Trial is a phase III, randomized, double-blind, placebo-controlled, parallel-group study evaluating the safety, tolerability, and efficacy of amifampridine in patients with MuSK-MG and a small sample of patients with AChR-MG. Amifampridine has received the Orphan Drug Designation from the Food and Drug Administration FDA for the treatment of patients with myasthenia gravis.
Investigational candidate RC18 is a fusion antibody created by RemeGen scientists to target signaling factors involved in the development and survival of B cells, the cell responsible for generating antibodies. RC18 is a fusion of a TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactors) protein and the IgG protein.
RC18 binds to BLyS (B lymphocyte stimulator) and APRIL (a proliferation-inducing ligand), preventing these cell-signaling molecules from binding to TACI proteins on the surface of the B cell. This inhibits the development and survival of mature B cells, preventing the formation of autoantibodies.
June is the Myasthenia Gravis Awareness Month that creates awareness regarding the myasthenia gravis (MG), supports the people living with Myasthenia Gravis, and creates connections for the MG community. This awareness month aims to boost the efforts regarding the fundraising, research, and advocacy to support people affected by Myasthenia Gravis.
Myasthenia Gravis is a disorder that occurred due to the breakdown in the communication between nerves and muscles because of an immunological problem. It caused the weakness and easy fatigue of the skeletal muscles used for the movement. It is characterized by the trouble talking, problems in walking up stairs or lifting objects, facial paralysis, difficulty in swallowing or chewing, fatigue, hoarse voice, drooping of eyelids, and double vision.
According to the National Organization for Rare Disorders (NORD), the prevalence of Myasthenia Gravis is approximately 14-40 per 100,000 individuals in the United States. It is most frequent among females in comparison to males. It affects people of any age group. It is most common in young adult women under 40 and older adult men over 60 years.
Scoliosis is a sideways curvature of the spine. It occurs most often during the growth spurt just before puberty. Several diseases such as cerebral palsy, muscular dystrophy, and other diseases, birth defects, spinal injuries, and genetic conditions lead to the development of Scoliosis.
Epidemiology Insights: Scoliosis
According to the American Associations of Neurological Surgeons, approximately, six to nine million people i.e. 2%-3% of the population are suffering from scoliosis in the United States.
Scoliosis can develop in infancy or early childhood.
The primary age of onset for scoliosis is 10-15 years old
Males and females are equally affected by scoliosis
Females are eight times more likely to progress to a curve magnitude that requires treatment
Every year, scoliosis patients make more than 600,000 visits to private physician offices
Around 30,000 children are fitted with a brace and 38,000 patients undergo spinal fusion surgery
Scoliosis is classified as the idiopathic, congenital or neuromuscular scoliosis based on etiology. Idiopathic Scoliosis is the most prevalent form of Scoliosis. Idiopathic Scoliosis accounts for 80% of all Scoliosis cases
Majority of the Scoliosis cases are observed among the adolescents
June is the Scoliosis Awareness Month that aims at highlighting the growing need for education, early detection, and awareness regarding scoliosis and its prevalence within the community. It unites scoliosis patients, families, physicians, clinicians, institutions, and related businesses in collaborative partnerships of local activities, events, and grassroots networking throughout the month.
Scoliosis is an abnormal side-to-side curvature of the spine. The spinal curve may develop as a single curve (shaped like the letter C) or as two curves (shaped like the letter S). It is often defined as spinal curvature in the “coronal” (frontal) plane. While the degree of curvature is measured on the coronal plane, scoliosis is actually a more complex, three-dimensional problem which involves the following planes:
The coronal plane is a vertical plane from head to foot and parallel to the shoulders, dividing the body into anterior (front) and posterior (back) sections. The sagittal plane divides the body into right and left halves. The axial plane is parallel to the plane of the ground and at right angles to the coronal and sagittal planes.
Scoliosis is hereditary among the people with scoliosis who are more likely to have children with scoliosis; however, there is no correlation between the severity of the curves from one generation to the next. In children and teens, scoliosis often does not have any noticeable symptoms and may not be noticeable until it has progressed significantly. Most cases of scoliosis are mild, but some spine deformities continue to get more severe as children grow. Severe scoliosis can be disabling. An especially severe spinal curve can reduce the amount of space within the chest, making it difficult for the lungs to function properly. The most common form of scoliosis appears in adolescents. It is known as adolescent idiopathic scoliosis. It can affect children from the age of 10 years.
The symptoms can include the head is slightly off center, the ribcage is not symmetrical, so the ribs may be at different heights and one hip is more prominent than the other. Furthermore, in infants, symptoms can include: a bulge on one side of the chest, consistently lying curved to one side (in babies), Problems with the heart and lungs, leading to shortness of breath and chest pain.
According to the American Association of Neurological Surgeons (AANS), about 80 percent of scoliosis cases have no identifiable cause. The condition is often diagnosed during the first seven years of a child’s life.
Neuromuscular Conditions: These affect the nerves and muscles and include cerebral palsy, poliomyelitis, and muscular dystrophy.
Congenital Scoliosis (present at birth): This is rare and occurs because the bones in the spine developed abnormally when the fetus was growing inside the mother.
Specific genes: At least one gene is thought to be involved in scoliosis.
Leg length: If one leg is longer than the other, the individual may develop scoliosis.
Syndromic scoliosis: Scoliosis can develop as part of another disease, including neurofibromatosis and Marfan’s syndrome.
Osteoporosis: This can cause secondary scoliosis due to bone degeneration.
There are certain risk factors associated with scoliosis include: age, gender & genetics etc. are explained below:
Age: Signs and symptoms often start during a growth spurt just before puberty.
Gender: Females have a higher risk in comparison to the males
Genetics: People with scoliosis may have a close relative with the condition.
Scoliosis is confirmed through a physical examination, an x-ray, spinal radiograph, CT scan or MRI. The curve is measured by the Cobb Method and is diagnosed in terms of severity by the number of degrees. A positive diagnosis of scoliosis is made based on a coronal curvature measured on a posterior-anterior radiograph of greater than 10 degrees. In general, a curve is considered significant if it is greater than 25 to 30 degrees. Curves exceeding 45 to 50 degrees are considered severe and often require more aggressive treatment.
A standard exam that is sometimes used by pediatricians and in grade school screenings is called the Adam’s Forward Bend Test. During this test, the patient leans forward with his or her feet together and bends 90 degrees at the waist. This is a simple initial screening test that can detect potential problems, but cannot determine accurately the exact type or severity of the deformity. The tests are required for an accurate and positive diagnosis.
Doctor would check the spine curvature and whether the shoulders and waist area are symmetrical or not.
Imaging tests doctor may order to look for scoliosis include:
X-ray: During this test, small amounts of radiation are used to create a picture of your spine.
MRI scan: This test uses radio and magnetic waves to get a detailed picture of bones and the tissue surrounding them.
CT scan: During this test, X-rays are taken at a variety of angles to get a 3-D picture of the body.
Bone scan: This test detects a radioactive solution injected into your blood that concentrates in areas of increased circulation, highlighting spinal abnormalities.
Treatment of scoliosis is based on the severity of the curve and the chances of the curve getting worse. Certain types of scoliosis have a greater chance of getting worse, so the type of scoliosis also helps to determine the proper treatment. There are three main categories of treatment i.e. observation, bracing (for example, thoracolumbosacral orthosis or TLSO back brace), and surgery. Consequently, there are treatments available that do not involve surgery, but in some individuals, surgery may be their best option.
In many children with scoliosis, the spinal curve is mild enough to not require treatment. However, if the doctor is worried that the curve may be increasing, he or she may wish to examine the child every four to six months throughout adolescence.
In adults with scoliosis, X-rays are usually recommended once every five years, unless symptoms are getting progressively worse.
Braces are only effective in patients who have not reached skeletal maturity. If the child is still growing and his or her curve is between 25 degrees and 40 degrees, a brace may be recommended to prevent the curve from progressing. There have been improvements in brace design and the newer models fit under the arm, not around the neck. There are several different types of braces available. For optimal effectiveness, the brace should be checked regularly to assure a proper fit and may need to be worn 16 to 23 hours every day until growth stops.
In children, the two primary goals of surgery are to stop the curve from progressing during adulthood and to diminish spinal deformity. Most experts would recommend surgery only when the spinal curve is greater than 40 degrees and there are signs of progression. This surgery can be done using an anterior approach (through the front) or a posterior approach (through the back) depending on the particular case.
A number of factors can lead to increased surgical-related risks in older adults with degenerative scoliosis. These factors include the following: advanced age, being a smoker, being overweight and the presence of other health/medical problems. In general, both surgery and recovery time are expected to be longer in older adults with scoliosis.
Following surgical procedures are used for the treatment of scoliosis
Posterior approach: The most frequently performed surgery for adolescent idiopathic scoliosis involves posterior spinal fusion with instrumentation and bone grafting. This is performed through the back while the patient lies on his or her stomach.
Anterior approach: The patient lies on his or her side during the surgery. The surgeon makes incisions in the patient’s side, deflates the lung and removes a rib in order to reach the spine. Video-assisted thoracoscopic (VAT) surgery offers enhanced visualization of the spine and is a less invasive surgery than an open procedure. The anterior spinal approach has several potential advantages: better deformity correction, quicker patient rehabilitation, improved spine mobilization and fusion of fewer segments.
Decompressive laminectomy: The laminae (roof) of the vertebrae are removed to create more space for the nerves. A spinal fusion with or without spinal instrumentation is often recommended when scoliosis and spinal stenosis are present. Various devices (like screws or rods) may be used to enhance fusion and support unstable areas of the spine.
Minimally invasive surgery (MIS) : Fusion can sometimes be performed via smaller incisions through MIS. The use of advanced fluoroscopy (X-ray imaging during surgery) and endoscopy (camera technology) has improved the accuracy of incisions and hardware placement, minimizing tissue trauma while enabling a MIS approach. It is important to keep in mind that not all cases can be treated in this manner and a number of factors contribute to the surgical method used.
The benefits of surgery should always be weighed carefully against its risks. Although a large percentage of scoliosis patients benefit from surgery, there is no guarantee that surgery will stop curve progression and symptoms in every individual.
Koselugo (selumetinib):AstraZeneca plc and Merck & Co., Inc.
Koselugo (selumetinib) is the first drug approved by the FDA for the treatment of pediatric patients, 2 years of age and older, with neurofibromatosis type 1 (NF1), a genetic disorder of the nervous system causing tumors to grow on nerves. The drug is an inhibitor of mitogen-activated protein kinases 1 and 2 (MEK1/2). Koselugo was granted with many designations: US FDA Breakthrough Therapy Designation in April 2019, Rare Pediatric Disease Designation in December 2019, Orphan Drug Designation in February 2018, EU orphan designation in August 2018 and Swissmedic Orphan Drug Status in December 2018 for the treatment of pediatric patients with NF1 PN.
Tukysa (tucatinib): Seattle Genetics
Tukysa (tucatinib) is an oral, small-molecule tyrosine kinase inhibitor (TKI) of HER2, a protein that contributes to cancer cell growth. The drug is approved in combination with trastuzumab and capecitabine for the treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting. Tukysa was approved by different regulatory bodies such as the US Food and Drug Administration (FDA) in collaboration with Health Canada, Australian Therapeutic Goods Administration (TGA), Swissmedic (SMC, Switzerland), and Health Sciences Authority (HSA, Singapore) in April 2020.
Pemazyre (pemigatinib): Innovent Biologics, Inc.
Pemazyre (pemigatinib) is the first and only FDA-approved treatment for the treatment of adults with previously treated, unresectable locally advanced, or metastatic cholangiocarcinoma. Pemazyre is a potent, selective, oral inhibitor of Fibroblast growth factor receptor (FGFR) 1, 2, and 3. The drug is marketed by Incyte in the United States. Incyte has granted Innovent Biologics rights to develop and commercialize pemigatinib in hematology and oncology in Mainland China, Hong Kong, Macau, and Taiwan. Incyte has retained all other rights to develop and commercialize pemigatinib outside of the United States.
Ongentys (opicapone): Neurocrine Biosciences, Inc.
Ongentys (opicapone) is the first and only approved Catechol-O-methyltransferase (COMT) inhibitor indicated for the treatment of Parkinson’s disease with off episodes, used as an adjunctive treatment to levodopa and carbidopa. It was developed by Portuguese pharmaceutical group BIAL. Neurocrine Biosciences entered an exclusive licensing agreement with BIAL for the development and commercialization of opicapone in North America in September 2017. BIAL is currently responsible for the marketing of Ongentys in the United Kingdom, Italy, Spain, Germany, and Portugal.
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
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.
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).
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.
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.
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)
Every year 30 May, is celebrated as the World Multiple Sclerosis Day to raise awareness regarding Multiple Sclerosis. It celebrates solidarity and hope for the future. It makes people closer free to move closer to a world free of MS.
Purpose of World Multiple Sclerosis Day
Building communities that support and nurture people affected by MS
Promoting self-care and healthy living with MS
Lobbying decision-makers for better services and effective treatment for people with MS
Connecting people affected by MS to MS research.
Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord that attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between the brain and the rest of the body. It causes permanent damage or deterioration of the nerves.