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

Kratom Seems Safe for Pain, Anxiety, Opioid Withdrawal

We know that, Mitragyna speciosa (commonly known as kratom is a tropical evergreen tree in the coffee family native to Southeast Asia. It is indigenous to Thailand, Indonesia, Malaysia, Myanmar, and Papua New Guinea, where it has been used in traditional medicines since at least the nineteenth century. Kratom has opioid properties and some stimulant-like effects.

Kratom is used for symptoms of pain, anxiety, depression, and opioid withdrawal, and serious adverse events are uncommon, according to a the results of a survey published online Feb. 3 in Drug and Alcohol Dependence.

Albert Garcia-Romeu, Ph.D., from the Johns Hopkins University School of Medicine in Baltimore, and colleagues conducted a cross-sectional online survey in 2017 involving 2,798 kratom users.

The researchers found that kratom was mainly taken orally in doses of 1 to 3 g (49 percent) and was most commonly used daily (59 percent). Kratom was used for pain, anxiety, and depression (91, 67, and 65 percent, respectively); effectiveness was highly rated. Overall, 41 percent (1,144 individuals) used kratom to stop or reduce prescription or illicit opioid use, with reports of decreased opioid withdrawal and craving in relation to use; continuous abstinence from opioids for more than one year was attributed to kratom use by 411 individuals. Adverse effects of kratom were reported by about one-third of respondents; these adverse effects were mainly rated as mild in severity and lasted ≤24 hours. Only 0.6 percent of participants sought treatment for adverse events. Two percent of participants met criteria for past-year moderate or severe kratom-related substance use disorder.

"Although our findings show kratom to be relatively safe according to these self-reports, unregulated medicinal supplements raise concerns with respect to contamination or higher doses of the active chemicals, which could increase negative side effects and harmful responses," Garcia-Romeu said in a statement.

Kratom Seems Safe for Pain, Anxiety, Opioid Withdrawal 

https://www.sciencedirect.com/science/article/abs/pii/S0376871620300144

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

FDA Approves Isturisa (osilodrostat) for the Treatment of Cushing’s Disease

The U.S. Food and Drug Administration today approved Isturisa (osilodrostat) oral tablets for adults with Cushing’s disease who either cannot undergo pituitary gland surgery or have undergone the surgery but still have the disease. 

Cushing’s disease is a rare disease in which the adrenal glands make too much of the cortisol hormone. Isturisa is the first FDA-approved drug to directly address this cortisol overproduction by blocking the enzyme known as 11-beta-hydroxylase and preventing cortisol synthesis.

“The FDA supports the development of safe and effective treatments for rare diseases, and this new therapy can help people with Cushing’s disease, a rare condition where excessive cortisol production puts them at risk for other medical issues,” said Mary Thanh Hai, M.D., acting director of the Office of Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research. “By helping patients achieve normal cortisol levels, this medication is an important treatment option for adults with Cushing’s disease.”

Cushing’s disease is caused by a pituitary tumor that releases too much of a hormone called adrenocorticotropin, which stimulates the adrenal gland to produce an excessive amount of cortisol. The disease is most common among adults between the ages of 30 to 50, and it affects women three times more often than men. Cushing’s disease can cause significant health issues, such as high blood pressure, obesity, type 2 diabetes, blood clots in the legs and lungs, bone loss and fractures, a weakened immune system and depression. Patients may have thin arms and legs, a round red full face, increased fat around the neck, easy bruising, striae (purple stretch marks) and weak muscles.

Isturisa’s safety and effectiveness for treating Cushing’s disease among adults was evaluated in a study of 137 adult patients (about three-quarters women) with a mean age of 41 years. The majority of patients either had undergone pituitary surgery that did not cure Cushing’s disease or were not surgical candidates. In the 24-week, single-arm, open-label period, all patients received a starting dose of 2 milligrams (mg) of Isturisa twice a day that could be increased every two weeks up to 30 mg twice a day. At the end of this 24-week period, about half of patients had cortisol levels within normal limits. After this point, 71 patients who did not need further dose increases and tolerated the drug for the last 12 weeks entered an eight-week, double-blind, randomized withdrawal study where they either received Isturisa or a placebo (inactive treatment). At the end of this withdrawal period, 86% of patients receiving Isturisa maintained cortisol levels within normal limits compared to 30% of patients taking the placebo.

The most common side effects reported in the clinical trial for Isturisa were adrenal insufficiency, headache, vomiting, nausea, fatigue and edema (swelling caused by fluid retention). Hypocortisolism (low cortisol levels), QTc prolongation (a heart rhythm condition) and elevations in adrenal hormone precursors (inactive substance converted into a hormone) and androgens (hormone that regulates male characteristics) may also occur in people taking Isturisa.

Isturisa is taken by mouth twice a day, in the morning and evening as directed by a health care provider. After treatment has started, a provider may re-evaluate dosage, depending upon the patient’s response.

Isturisa received Orphan Drug Designation, which is a special status granted to a drug intended to treat a rare disease or condition.

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

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FDA Approves Isturisa (osilodrostat) for the Treatment of Cushing’s Disease

FDA Approves Durysta (bimatoprost implant) to Lower Intraocular Pressure In Open-Angle Glaucoma or Ocular Hypertension Patients

Allergan plc (NYSE: AGN), a leading global pharmaceutical company with more than 70 years of heritage in eye care, announced the U.S. Food and Drug Administration (FDA) approval.  With this approval, Durysta becomes the first intracameral, biodegradable sustained-release implant indicated to reduce intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

"Today's FDA approval marks a breakthrough milestone for the glaucoma community and provides a much-needed option for patients challenged with topical drops or needing alternative options," said David Nicholson, Chief Research and Development Officer, Allergan. "At Allergan, our mission is to contribute meaningful strategies that help preserve people's vision, while ensuring that therapies are mindful of the realities of administration and compliance. As a commitment to the ongoing development of this innovation, Allergan has five ongoing Phase 3 studies with Durysta to support further potential FDA label enhancement and rest of the world approvals."

The FDA approval is based on results from the two 20-month (including 8-month extended follow up) Phase 3 ARTEMIS studies evaluating 1,122 subjects on the efficacy and safety of Durysta versus twice daily topical timolol drops, an FDA accepted comparator for registrational clinical trials, in patients with OAG or OHT. In the two Phase 3 ARTEMIS studies, Durysta reduced IOP by approximately 30 percent from baseline over the 12-week primary efficacy period, meeting the predefined criteria for non-inferiority to the study comparator.

"Millions of people are living with glaucoma, one of the leading causes of vision loss; however, new treatment options are needed to help doctors and patients better manage this disease," said Felipe Medeiros , M.D., Ph.D., Distinguished Professor of Ophthalmology and Vice-Chair for Technology, Director Clinical Research Unit, Department of Ophthalmology, Duke University. "The ARTEMIS trials demonstrated that Durysta lowered IOP in patients by approximately 30 percent and demonstrated a duration of effect through the 12-week primary efficacy period. As the first FDA-approved intracameral, biodegradable sustained-release implant providing continuous drug delivery, Durysta has the potential to significantly shift the paradigm for treating glaucoma."

With the launch of Durysta, Allergan proudly expands availability of Allergan EyeCue®, a proven reimbursement service for eye care professionals to facilitate patient benefit verification, savings program enrollment for eligible patients, and prior authorization (PA) assistance for Allergan Eye Care products.