FDA Approves Zeposia (ozanimod) for Relapsing Forms of Multiple Sclerosis

Myers Squibb Company (NYSE: BMY)  announced that the U.S. Food and Drug Administration (FDA) approved Zeposia (ozanimod) 0.92 mg for the treatment of adults with relapsing forms of multiple sclerosis (RMS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.1 Zeposia, an oral medication taken once daily, is the only approved sphingosine-1-phosphate (S1P) receptor modulator that offers RMS patients an initiation with no genetic test and no label-based first-dose observation required for patients.1,4,5 An up-titration scheme should be used to reach the maintenance dosage of Zeposia, as a transient decrease in heart rate and atrioventricular conduction delays may occur.

Multiple sclerosis (MS) is a disease in which the immune system attacks the protective myelin sheath that covers the nerves, creating damaging lesions that make it harder for signals to travel between each nerve cell.6,7 This “signal breakdown” can lead to symptoms and relapses.6,8

“With the FDA approval of Zeposia, appropriate patients with relapsing forms of multiple sclerosis will have another oral treatment option with meaningful efficacy to help address the disease’s hallmark relapses and brain lesions,”9 said Samit Hirawat, M.D., chief medical officer, Bristol Myers Squibb. “Zeposia has substantial clinical potential, and we are well positioned with our heritage in transformational science to ensure this innovative compound ultimately benefits as many patients as possible.”

The approval is based on data from the largest pivotal, head-to-head RMS studies with an active comparator to date: the randomized, active-controlled Phase 3 SUNBEAM™ (safety and efficacy of Zeposia versus interferon beta-1a in relapsing multiple sclerosis) and RADIANCE™ (safety and efficacy of the selective sphingosine 1-phosphate receptor modulator Zeposia in relapsing multiple sclerosis) Part B clinical trials of more than 2,600 adults.1,2,3,10 In both trials – as compared to AVONEX® (interferon beta-1a), Zeposia delivered powerful efficacy as measured by annualized relapse rate (ARR), as well as on the number and size of brain lesions.1,2,3

• Zeposia demonstrated a relative reduction in ARR versus AVONEX of 48% through one year and 38% at two years (absolute ARR of 0.18 versus 0.35 and 0.17 versus 0.28, respectively).1,2,3
• At one year, treatment with Zeposia reduced the number of T1-weighted gadolinium-enhanced (GdE) brain lesions more than AVONEX (0.16 vs 0.43), a relative reduction of 63%, and reduced the number of new or enlarging T2 lesions (1.47 vs. 2.84), a relative reduction of 48%.1,3
• At two years, treatment with Zeposia reduced the number of T1-weighted gadolinium-enhanced (GdE) brain lesions more than AVONEX (0.18 vs 0.37), a relative reduction of 53%.1,2 Zeposia also reduced the number of new or enlarging T2 lesions vs AVONEX (1.84 vs 3.18), a relative reduction of 42%.1,2

There was no statistically significant difference in the three-month and six-month confirmed disability progression between Zeposia- and AVONEX- treated patients over two years.1

Zeposia demonstrated acceptable safety and tolerability in the Phase 3 SUNBEAM and RADIANCE Part B trials.1,2,3 Zeposia is contraindicated in patients who in the last six months experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure; patients who have a presence of Mobitz type II second or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial, unless the patient has a functioning pacemaker; patients with severe untreated sleep apnea; and patients taking a monoamine oxidase inhibitor.1 Zeposia is associated with the following Warnings and Precautions: increased risk of infections, bradyarrhythmia and atrioventricular conduction delays, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, posterior reversible encephalopathy syndrome, additive immunosuppressive effects from prior immune-modulating treatments, severe increase in disability after stopping Zeposia, and immune system effects after stopping Zeposia.1 Please see Important Safety Information for additional details. The most common adverse reactions (incidence ≥4%) were upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.1

Before initiation of treatment with Zeposia, all patients require assessments including a recent complete blood count including lymphocyte count (within six months or after discontinuation of prior MS therapy), an ECG to determine whether preexisting conduction abnormalities are present, a recent liver function test (within six months), and consideration of current and prior medications, including vaccinations.¹ For patients with a history of uveitis or macular edema, an ophthalmic assessment is required.

Treatment for relapsing forms of multiple sclerosis is critical to address this devastating neurological disease.11 I’m excited, with the introduction of Zeposia, I will have a new oral option to offer my RMS patients that has demonstrated efficacy and safety,”1 said Bruce Cree, M.D., Ph.D., M.A.S., professor of clinical neurology, University of California San Francisco (UCSF) Weill Institute for Neurosciences and clinical research director, UCSF MS Center.

“Multiple sclerosis is an unpredictable and often disabling disease that affects nearly one million people in the United States.9,12 Ongoing treatment with disease-modifying therapy can reduce the number of disease attacks,”11 said Bruce Bebo, executive vice president of research, National Multiple Sclerosis Society. “Each person can respond differently to these medications, which is why having treatment options is so important. We are pleased that there will now be another effective treatment option for people with MS.”

As the country’s healthcare system is dealing with the unprecedented COVID-19 pandemic, Bristol Myers Squibb has made the decision to delay commercialization of Zeposia. The Company made the decision based on what’s in the best health interest of our patients, customers and employees. Bristol Myers Squibb will continue to monitor the environment and will partner with the neurology community to inform launch timing.

A Marketing Authorization Application for Zeposia for the treatment of adults with relapsing-remitting multiple sclerosis in the European Union is currently under review with the European Medicines Agency (EMA). A regulatory decision from the EMA is expected in the first half of 2020.

https://en.wikipedia.org/wiki/Ozanimod

FDA Approves Zeposia (ozanimod) for Relapsing Forms of Multiple Sclerosis

FDA Approves Vumerity (diroximel fumarate) for Multiple Sclerosis

 Biogen Inc. (Nasdaq: BIIB) and Alkermes plc (Nasdaq: ALKS),  announced  the U.S. Food and Drug Administration (FDA) approval of Vumerity (diroximel fumarate), a novel oral fumarate with a distinct chemical structure, for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. Biogen holds the exclusive, worldwide license to commercialize Vumerity and intends to make it available in the United States in the near future.

“The FDA’s approval of Vumerity delivers on Biogen’s commitment to pursue new therapies that may provide meaningful impact for people living with relapsing MS, and we look forward to bringing it to the MS community as an additional treatment option,” said Alfred Sandrock, Jr., M.D., Ph.D., executive vice president, research and development, and chief medical officer at Biogen. “Vumerity is a novel fumarate that offers the well-characterized efficacy of Tecfidera® (dimethyl fumarate) and has been studied for improved patient-reported gastrointestinal tolerability.”

“The approval of Vumerity for relapsing MS marks the culmination of a multi-year development program and is the latest milestone in our mission to develop new treatments for patients living with chronic central nervous system disorders,” said Craig Hopkinson, M.D., chief medical officer and senior vice president of medicines development and medical affairs at Alkermes. “We are grateful to the patients and study investigators who have participated in our Vumerity clinical trials and we look forward to working with our collaboration partners at Biogen to make this new treatment available to patients.”

The FDA approval of Vumerity was based on a New Drug Application (NDA) submitted under the 505(b)(2) filing pathway. It included data from pharmacokinetic bridging studies comparing Vumerity and Tecfidera to establish bioequivalence, and relied, in part, on the FDA’s findings of safety and efficacy for Tecfidera.

The NDA submission also included interim exposure and safety findings from EVOLVE-MS-1, an ongoing, Phase 3, single-arm, open-label, two-year safety study evaluating Vumerity in patients with relapsing-remitting MS. Interim results from EVOLVE-MS-1 at the time of NDA submission included a low overall rate of Vumerity treatment discontinuation due to adverse events (6.3 percent), and a rate of less than one percent of patients who discontinued Vumerity treatment due to gastrointestinal (GI) adverse events. Additional exploratory efficacy endpoints in the ongoing EVOLVE-MS-1 study showed changes in clinical and radiological measures compared to baseline.

“MS is a heterogeneous disease, and real-world patient circumstances can vary, reinforcing the benefits of having therapeutic choices to support the diverse range of treatment considerations,” said Robert Naismith, M.D., professor of neurology, Washington University School of Medicine in St. Louis. “Throughout its clinical development program, Vumerity has demonstrated a desirable therapeutic profile, making it a compelling new option for patients.”

“MS is a lifelong disease that has a significant impact on the people affected and their caregivers. We are encouraged by the progress being made in the treatment of MS, and pleased that another treatment option will soon be available,” said Bruce Bebo, Ph.D., executive vice president, research, National MS Society. “It’s important for people with MS to have treatments that are both efficacious and tolerable to help manage their disease.”

Under the terms of the license and collaboration agreement between Biogen and Alkermes, Biogen will pay Alkermes $150 million in connection with the FDA’s approval of Vumerity. Biogen plans to account for this milestone payment as an asset that will be amortized over the expected useful life of the product. Alkermes is also entitled to receive a mid-teens percentage royalty on worldwide net commercial sales of Vumerity, subject, under certain circumstances, to minimum annual payments for the first five years following FDA approval and customary reductions as set forth in the agreement.

https://www.drugbank.ca/drugs/DB14783

FDA Approves Mavenclad (cladribine) Tablets for Multiple Sclerosis

In continuation of my update on cladribine

The U.S. Food and Drug Administration,    approved Mavenclad (cladribine) tablets to treat relapsing forms of multiple sclerosis (MS) in adults, to include relapsing-remitting disease and active secondary progressive disease. Mavenclad is not recommended for MS patients with clinically isolated syndrome. Because of its safety profile, the use of Mavenclad is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS.

“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “The approval of Mavenclad represents an additional option for patients who have tried another treatment without success.”

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communications between the brain and other parts of the body. Most people experience their first symptoms of MS between the ages of 20 and 40. MS is among the most common causes of neurological disability in young adults and occurs more frequently in women than in men.

For most people, MS starts with a relapsing-remitting course, in which episodes of worsening function (relapses) are followed by recovery periods (remissions). These remissions may not be complete and may leave patients with some degree of residual disability. Many, but not all, patients with MS experience some degree of persistent disability that gradually worsens over time. In some patients, disability may progress independent of relapses, a process termed secondary progressive multiple sclerosis (SPMS). In the first few years of this process, many patients continue to experience relapses, a phase of the disease described as active SPMS. Active SPMS is one of the relapsing forms of MS, and drugs approved for the treatment of relapsing forms of MS can be used to treat active SPMS.

The efficacy of Mavenclad was shown in a clinical trial in 1,326 patients with relapsing forms of MS who had least one relapse in the previous 12 months. Mavenclad significantly decreased the number of relapses experienced by these patients compared to placebo. Mavenclad also reduced the progression of disability compared to placebo.

Mavenclad must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Mavenclad has a Boxed Warning for an increased risk of malignancy and fetal harm. Mavenclad is not to be used in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, health care professionals should evaluate the benefits and risks of the use of Mavenclad on an individual patient basis. Health care professionals should follow standard cancer screening guidelines in patients treated with Mavenclad. The drug should not be used in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception during treatment and for six months after the course of therapy because of the potential for fetal harm. Mavenclad should be stopped if the patient becomes pregnant.

Other warnings include the risk of decreased lymphocyte (white blood cell) counts; lymphocyte counts should be monitored before, during and after treatment. Mavenclad may increase the risk of infections; health care professionals should screen patients for infections and treatment with Mavenclad should be delayed if necessary. Mavenclad may cause hematologic toxicity and bone marrow suppression so health care professionals should measure a patient’s complete blood counts before, during and after therapy. The drug has been associated with graft-versus-host-disease following blood transfusions with non-irradiated blood. Mavenclad may cause liver injury and treatment should be interrupted or discontinued, as appropriate, if clinically significant liver injury is suspected.

The most common adverse reactions reported by patients receiving Mavenclad in the clinical trials include upper respiratory tract infections, headache and decreased lymphocyte counts. 

Ref : https://en.wikipedia.org/wiki/Cladribine

FDA Approves Mavenclad (cladribine) Tablets for Multiple Sclerosis

FDA Approves Mavenclad (cladribine) Tablets for Multiple Sclerosis

In continuation of my update on cladribine

The U.S. Food and Drug Administration,    approved Mavenclad (cladribine) tablets to treat relapsing forms of multiple sclerosis (MS) in adults, to include relapsing-remitting disease and active secondary progressive disease. Mavenclad is not recommended for MS patients with clinically isolated syndrome. Because of its safety profile, the use of Mavenclad is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS.

“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “The approval of Mavenclad represents an additional option for patients who have tried another treatment without success.”

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communications between the brain and other parts of the body. Most people experience their first symptoms of MS between the ages of 20 and 40. MS is among the most common causes of neurological disability in young adults and occurs more frequently in women than in men.

For most people, MS starts with a relapsing-remitting course, in which episodes of worsening function (relapses) are followed by recovery periods (remissions). These remissions may not be complete and may leave patients with some degree of residual disability. Many, but not all, patients with MS experience some degree of persistent disability that gradually worsens over time. In some patients, disability may progress independent of relapses, a process termed secondary progressive multiple sclerosis (SPMS). In the first few years of this process, many patients continue to experience relapses, a phase of the disease described as active SPMS. Active SPMS is one of the relapsing forms of MS, and drugs approved for the treatment of relapsing forms of MS can be used to treat active SPMS.

The efficacy of Mavenclad was shown in a clinical trial in 1,326 patients with relapsing forms of MS who had least one relapse in the previous 12 months. Mavenclad significantly decreased the number of relapses experienced by these patients compared to placebo. Mavenclad also reduced the progression of disability compared to placebo.

Mavenclad must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Mavenclad has a Boxed Warning for an increased risk of malignancy and fetal harm. Mavenclad is not to be used in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, health care professionals should evaluate the benefits and risks of the use of Mavenclad on an individual patient basis. Health care professionals should follow standard cancer screening guidelines in patients treated with Mavenclad. The drug should not be used in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception during treatment and for six months after the course of therapy because of the potential for fetal harm. Mavenclad should be stopped if the patient becomes pregnant.

Other warnings include the risk of decreased lymphocyte (white blood cell) counts; lymphocyte counts should be monitored before, during and after treatment. Mavenclad may increase the risk of infections; health care professionals should screen patients for infections and treatment with Mavenclad should be delayed if necessary. Mavenclad may cause hematologic toxicity and bone marrow suppression so health care professionals should measure a patient’s complete blood counts before, during and after therapy. The drug has been associated with graft-versus-host-disease following blood transfusions with non-irradiated blood. Mavenclad may cause liver injury and treatment should be interrupted or discontinued, as appropriate, if clinically significant liver injury is suspected.

The most common adverse reactions reported by patients receiving Mavenclad in the clinical trials include upper respiratory tract infections, headache and decreased lymphocyte counts. 

Ref : https://en.wikipedia.org/wiki/Cladribine

FDA Approves Mavenclad (cladribine) Tablets for Multiple Sclerosis

Mavenclad Approved for Multiple Sclerosis

In continuation of my update on Mavenclad (cladribine)

  

Mavenclad (cladribine) tablets have been approved by the U.S. Food and Drug Administration to treat relapsing multiple sclerosis (MS) in adults.

An agency news release said the drug is recommended for people who have had an inadequate response to, or are unable to tolerate, another medication approved for MS. Mavenclad is not sanctioned for a form of MS called clinically isolated syndrome.

MS is a chronic autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. Most people have initial symptoms between ages 20 and 40, more often in women than men. The disease progresses over time and typically leads to lifelong disability.

Mavenclad's effectiveness was shown in clinical studies involving 1,326 people with relapsing forms of MS who had least one relapse in the prior 12 months. The drug significantly decreased the number of relapses compared to a placebo, the FDA said.

Mavenclad must be dispensed with a patient medication guide that describes the drug's uses and risks. The medication's label includes a boxed warning of increased risk of cancer, worsening existing cancer, and fetal harm. The drug should not be used in pregnant women and among people of reproductive age who do not use contraception during treatment and for six months afterward, the FDA said. Mavenclad should be stopped if the user becomes pregnant.

Other significant warnings include a risk of a drop in white blood cells called lymphocytes, infections, bone marrow suppression and liver injury. The most common adverse reactions include upper respiratory tract infection and headache.

https://en.wikipedia.org/wiki/Cladribine

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Mavenclad Approved for Multiple Sclerosis 

Celgene Submits Application to FDA for Ozanimod for the Treatment of Relapsing Forms of Multiple Sclerosis

In continuation of my update on ozanimod

Celgene Corporation (NASDAQ:CELG)  announced that the Company has submitted a New Drug Application to the U.S. Food and Drug Administration (FDA) for ozanimod for the treatment of adults with relapsing forms of multiple sclerosis (RMS). Ozanimod is an oral, sphingosine 1-phosphate (S1P) receptor modulator, which binds with high affinity selectively to S1P subtypes 1 (S1P1) and 5 (S1P5).

The pivotal efficacy and safety data provided in the application result from the SUNBEAM™ and RADIANCE™ Part B phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trials.

“New oral treatment options with differentiated profiles like ozanimod are needed to help address an unmet need for people with relapsing forms of MS,” said Jay Backstrom, M.D., Chief Medical Officer for Celgene. “With concurrent applications in the U.S. and EU, we look forward to advancing this promising medicine through the regulatory review process to provide a new option for the treatment of RMS in 2020.”

Earlier this month, the Company also submitted a Marketing Authorization Application to the European Medicines Agency for adults with relapsing-remitting multiple sclerosis.

Ozanimod is an investigational compound that is not approved for any use in any country.

About SUNBEAM™

SUNBEAM is a pivotal, phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of two doses of oral ozanimod (0.92 mg and 0.46 mg, equivalent to 1 mg and 0.5 mg ozanimod HCI respectively) against weekly intramuscular interferon beta-1a (Avonex®) for at least a 12-month treatment period. The study included 1,346 people living with RMS across 152 sites in 20 countries.

The primary endpoint of the trial was annualized relapse rates (ARR) during the treatment period. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 12 months, number of gadolinium-enhanced brain MRI lesions at month 12 and percent change from baseline in whole brain volume at month 12. Cortical grey and thalamic volume changes were also prospectively assessed versus active comparator.

An analysis of the time to onset of 3-month confirmed disability progression was pre-specified using pooled data from both the SUNBEAM and RADIANCE Part B phase 3 trials.

About RADIANCE™

RADIANCE Part B is a pivotal, phase 3, multicenter, randomized, double-blind, double-dummy, active-controlled trial evaluating the efficacy, safety and tolerability of two doses of oral ozanimod (0.92 mg and 0.46 mg, equivalent to 1 mg and 0.5 mg ozanimod HCI respectively) against weekly intramuscular interferon beta-1a (Avonex®) over a 24-month treatment period. The study included 1,320 people living with RMS across 150 sites in 21 countries.

The primary endpoint of the trial was ARR over 24 months. The secondary MRI endpoints included the number of new or enlarging hyperintense T2-weighted brain MRI lesions over 24 months, number of gadolinium-enhanced brain MRI lesions at month 24 and percent change from baseline in whole brain volume at month 24. Cortical grey and thalamic volume changes were also prospectively assessed versus active comparator.

An analysis of the time to onset of 3-month confirmed disability progression was pre-specified using pooled data from both the SUNBEAM and RADIANCE Part B phase 3 trials.

About Ozanimod

Ozanimod is an oral, sphingosine 1-phosphate (S1P) receptor modulator, which binds with high affinity selectively to S1P subtypes 1 (S1P1) and 5 (S1P5). Ozanimod causes lymphocyte retention in lymphoid tissues. The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis is unknown, but may involve the reduction of lymphocyte migration into the central nervous system.

Ozanimod is in development for immune-inflammatory indications including RMS, ulcerative colitis and Crohn's disease.

https://en.wikipedia.org/wiki/Ozanimod

Celgene Submits Application to FDA for Ozanimod for the Treatment of Relapsing Forms of Multiple Sclerosis

FDA Approves Mavenclad (cladribine) Tablets for Multiple Sclerosis

In continuation of my update on Cladribine

The U.S. Food and Drug Administration,  approved Mavenclad (cladribine) tablets to treat relapsing forms of multiple sclerosis (MS) in adults, to include relapsing-remitting disease and active secondary progressive disease. Mavenclad is not recommended for MS patients with clinically isolated syndrome. Because of its safety profile, the use of Mavenclad is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS.

“We are committed to supporting the development of safe and effective treatments for patients with multiple sclerosis,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “The approval of Mavenclad represents an additional option for patients who have tried another treatment without success.”

MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communications between the brain and other parts of the body. Most people experience their first symptoms of MS between the ages of 20 and 40. MS is among the most common causes of neurological disability in young adults and occurs more frequently in women than in men.

For most people, MS starts with a relapsing-remitting course, in which episodes of worsening function (relapses) are followed by recovery periods (remissions). These remissions may not be complete and may leave patients with some degree of residual disability. Many, but not all, patients with MS experience some degree of persistent disability that gradually worsens over time. In some patients, disability may progress independent of relapses, a process termed secondary progressive multiple sclerosis (SPMS). In the first few years of this process, many patients continue to experience relapses, a phase of the disease described as active SPMS. Active SPMS is one of the relapsing forms of MS, and drugs approved for the treatment of relapsing forms of MS can be used to treat active SPMS.

The efficacy of Mavenclad was shown in a clinical trial in 1,326 patients with relapsing forms of MS who had least one relapse in the previous 12 months. Mavenclad significantly decreased the number of relapses experienced by these patients compared to placebo. Mavenclad also reduced the progression of disability compared to placebo.

Mavenclad must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks. Mavenclad has a Boxed Warning for an increased risk of malignancy and fetal harm. Mavenclad is not to be used in patients with current malignancy. In patients with prior malignancy or with increased risk of malignancy, health care professionals should evaluate the benefits and risks of the use of Mavenclad on an individual patient basis. Health care professionals should follow standard cancer screening guidelines in patients treated with Mavenclad. The drug should not be used in pregnant women and in women and men of reproductive potential who do not plan to use effective contraception during treatment and for six months after the course of therapy because of the potential for fetal harm. Mavenclad should be stopped if the patient becomes pregnant.

Other warnings include the risk of decreased lymphocyte (white blood cell) counts; lymphocyte counts should be monitored before, during and after treatment. Mavenclad may increase the risk of infections; health care professionals should screen patients for infections and treatment with Mavenclad should be delayed if necessary. Mavenclad may cause hematologic toxicity and bone marrow suppression so health care professionals should measure a patient’s complete blood counts before, during and after therapy. The drug has been associated with graft-versus-host-disease following blood transfusions with non-irradiated blood. Mavenclad may cause liver injury and treatment should be interrupted or discontinued, as appropriate, if clinically significant liver injury is suspected.

The most common adverse reactions reported by patients receiving Mavenclad in the clinical trials include upper respiratory tract infections, headache and decreased lymphocyte counts. 

Ref : https://en.wikipedia.org/wiki/Cladribine

FDA Approves Mavenclad (cladribine) Tablets for Multiple Sclerosis

Alkermes and Biogen Announce U.S. Food and Drug Administration Acceptance of Diroximel Fumarate New Drug Application for Multiple Sclerosis

   

Alkermes plc (Nasdaq: ALKS) and Biogen Inc. (Nasdaq: BIIB)  announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for diroximel fumarate (BIIB098), a novel oral fumarate in development for the treatment of relapsing forms of multiple sclerosis (MS). The NDA has been assigned a PDUFA (Prescription Drug User Fee Act) target action date in the fourth quarter of 2019. If approved, Biogen intends to market diroximel fumarate under the brand name VUMERITY™, which has been conditionally accepted by the FDA and will be confirmed upon approval.

“The NDA filing acceptance for diroximel fumarate further demonstrates the productive collaboration between Alkermes and Biogen and brings us closer to our shared goal of offering a new therapeutic option for people with MS,” said Craig Hopkinson, M.D., chief medical officer and senior vice president, medicines development and medical affairs at Alkermes. “We believe diroximel fumarate has the potential to be a meaningful new offering for patients with MS, and we look forward to continued engagement with the FDA throughout the review process.”

“For more than two decades Biogen has been at the forefront of delivering new medicines to MS patients,” said Michael Ehlers, M.D., Ph.D., executive vice president, research and development at Biogen. “We are encouraged by the FDA’s acceptance of the NDA for diroximel fumarate, which we believe could help elevate the treatment of this complex and often debilitating disease.”

Alkermes is seeking approval of diroximel fumarate under the 505(b)(2) regulatory pathway, referencing Biogen’s dimethyl fumarate data. The NDA submission includes data from EVOLVE-MS-1, a Phase 3, open-label, two-year safety study in relapsing-remitting MS (RRMS) patients. It is hypothesized that the distinct chemical structure of diroximel fumarate may impact its gastrointestinal (GI) tolerability. Alkermes is conducting EVOLVE-MS-2, a head-to-head GI tolerability study versus dimethyl fumarate, with results expected later this year.

About the Diroximel Fumarate Clinical Development Program

The key components of the clinical development program of diroximel fumarate include the EVOLVE-MS-1 study, a Phase 3, open-label, two-year safety study in relapsing-remitting MS (RRMS) patients, along with pharmacokinetic bridging studies comparing diroximel fumarate and dimethyl fumarate. In addition, Alkermes is conducting the EVOLVE-MS-2 study in patients with RRMS, a five-week, head-to-head gastrointestinal (GI) tolerability study versus dimethyl fumarate.

About Diroximel Fumarate

Diroximel fumarate (BIIB098) is a novel oral fumarate candidate in development for the treatment of relapsing forms of MS. Diroximel fumarate is designed to rapidly convert to monomethyl fumarate in the body and may have the potential to offer differentiated GI tolerability due to its chemical structure as compared to dimethyl fumarate.

Alkermes and Biogen Announce U.S. Food and Drug Administration Acceptance of Diroximel Fumarate New Drug Application for Multiple Sclerosis

TSRI scientists shed light on molecular workings of MS drug

In continuation of my update on Tecfidera

A study by scientists at The Scripps Research Institute (TSRI) has helped to de-mystify the molecular workings of the multiple sclerosis (MS) drug Tecfidera®. The drug is the most widely prescribed pill-based therapy for MS, but its biological mechanism remains mysterious.

Using a new TSRI technology that can quickly reveal a drug's protein targets, the scientists showed that Tecfidera® interacts with multiple T cell proteins, in some cases inhibiting their activity, and helping to suppress the T cell activation that is a key feature of MS flare-ups.

"This new technology has given us insights into the therapeutic modulation of the immune system that we could not have obtained with standard approaches," said co-senior author John R. Teijaro, an assistant professor at TSRI.

The study was reported recently in Science Signaling.

Treatment for an Autoimmune Disease

MS is an autoimmune disease of the brain featuring damage to nerve fibers and producing a range of symptoms, including tingling in the extremities, muscle weakness, muscle spasms, visual problems and mood instability. About 400,000 people in the United States and about 2.5 million worldwide have MS, mostly in a form with intermittent flare-ups of symptoms—which can start to worsen inexorably.

Two large clinical trials published in 2012 found that Tecfidera® is almost twice as effective as an older standard MS drug at reducing the rate of flare-ups. It also appears to slow the disease's progression. But how the drug works has never been clear.

Despite its recent (2013) US Food and Drug Administration approval for MS, the drug is neither new nor high-tech. It is a relatively simple organic compound, dimethyl fumarate (DMF), that has been in the biomedical literature for decades. It was once used in Europe to prevent mold growth in sofas during storage and shipping, although the European Union banned it from consumer products in 2009 after it was linked to severe allergic skin reactions. It has proved more useful as a pharmaceutical: since the 1990s it has been an effective treatment—as the main ingredient in the drug Fumaderm®—for the autoimmune skin disease psoriasis. Success against psoriasis led to its investigation as a potential MS drug.

Until recently, the leading theory was that DMF works against MS primarily by unleashing the activity of a protein called Nrf2, which helps protect the brain from autoimmune damage by marshaling a powerful anti-oxidant response and which may also reduce immune system activation. Studies published in the past year have suggested, however, that DMF works principally by reducing immune system activity and does so independently of Nrf2. In recent years, there have also have been several reports among patients taking Fumaderm® or Tecfidera® of a potentially fatal viral brain infection called progressive multifocal leukoencephalopathy, which normally occurs only in people whose immune systems have been seriously weakened.

New plant-derived oral drug can prevent progression of multiple sclerosis

   

An international research team has demonstrated that a new plant-derived drug can block the progression of multiple sclerosis (MS).

University of Queensland researcher Dr Christian Gruber said the breakthrough could be a step forward in preventing and treating MS and other autoimmune diseases.

"This is a really exciting discovery because it may offer a whole new quality of life for people with this debilitating disease," he said.

The new drug is expected to be taken by mouth, in contrast to some current MS treatments where patients need to have frequent injections.

MS is a chronic incurable condition marked by attacks that bring gradual deterioration in the patient's health. About 23,000 people are affected in Australia and 2.5 million worldwide.

Dr Gruber said the new drug -- named T20K -- was extracted from a traditional medicinal plant, the Oldenlandia affinis.

The drug treatment had been successful in an animal model, and patent applications filed in several countries.

"Phase one clinical trials could begin as early as 2018," Dr Gruber said.

"Licences have been assigned to Cyxone, a company established last year to develop this new class of drugs for the treatment of autoimmune diseases.

"Cyxone's immediate focus is on bringing T20K through the pre-clinical program required for delivering a safe, orally active drug."

Dr Gruber said the new treatment arose from a synthesised plant peptide, a class of drugs known as cyclotides.

"Cyclotides are present in a range of common plants, and they show significant potential for the treatment of auto immune diseases," he said.

"The T20K peptides exhibit extraordinary stability and chemical features that are ideally what you want in an oral drug candidate."

New plant-derived oral drug can prevent progression of multiple sclerosis: An international research team has demonstrated that a new plant-derived drug can block the progression of multiple sclerosis (MS).