FDA Approves Mayzent (siponimod) for Secondary Progressive Multiple Sclerosis

 Novartis  announced that the US Food and Drug Administration (FDA) has approved Mayzent (siponimod) for the treatment of adults with relapsing forms of multiple sclerosis, including secondary progressive multiple sclerosis (SPMS) with active disease, relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS)*. SPMS is a debilitating form of multiple sclerosis (MS) characterized by progressive and irreversible neurological disability[4]. Mayzent is expected to be available in the US in approximately one week**. Patients will not require a first dose observation (FDO, cardiac monitoring upon initiation) unless they have certain pre-existing cardiac conditions.

"One of the most important aims of MS treatment is delaying disability progression and preserving cognition," said Paul Hudson, Chief Executive Officer, Novartis Pharmaceuticals. "With Mayzent, SPMS patients with active disease will have access to the first effective oral therapy directed towards disease progression, even when MS transitions to a stage where deterioration is less dependent on the usual relapse activity. Mayzent is a testament to the Novartis mission to reimagine medicine. We are delighted that our ongoing commitment to stop MS has led to a much awaited treatment for these patients in need."

Most patients transition from RRMS to SPMS over time[2]. Therefore, starting therapy early is critical for patients to help slow the rate of disability progression. Disability progression most frequently includes - but is not limited to - an impact on ambulation, which could lead to patients needing a walking aid or a wheelchair, bladder dysfunction and cognitive decline[5]. 

"We are grateful that there is a new treatment option for adults with active secondary progressive MS," said Bruce Bebo, PhD, Executive Vice President, Research, US National MS Society. "We are hopeful this approval will stimulate a conversation between patients and healthcare professionals about disability progression after relapsing remitting MS and its early management."

The approval of Mayzent is based on groundbreaking data from the Phase III EXPAND study, a randomized, double-blind, placebo-controlled study, comparing the efficacy and safety of Mayzent versus placebo in people living with SPMS. Patients enrolled in EXPAND were representative of a typical SPMS population: at study initiation, patients had a mean age of 48 years, had been living with MS for approximately 16 years and more than 50% had a median Expanded Disability Status Scale (EDSS) score of 6.0 and relied on a walking aid[3]. Mayzent significantly reduced the risk of three-month confirmed disability progression (CDP) (primary endpoint; 21% reduction versus placebo, p=0.013; 33% reduction versus placebo in patients with relapse activity in the two years prior to screening, p=0.0100)[3]. Additionally, Mayzent meaningfully delayed the risk of six-month CDP (26% versus placebo, p=0.0058) and reduced the annualized relapse rate (ARR) by 55%[3]. Furthermore, EXPAND showed significant favorable outcomes in other relevant measures of MS disease activity, including cognition, MRI disease activity and brain volume loss (brain shrinkage)[3].

Most common adverse reactions (incidence greater than 10%) were headache, hypertension, and transaminase increase.

"With the approval of Mayzent, we now have a much-needed therapeutic option to address SPMS with active disease," said EXPAND Steering Committee member Bruce Cree, MD, PhD, MAS, Clinical Research Director and George A. Zimmermann Endowed Professor in Multiple Sclerosis, University of California, San Francisco, School of Medicine. "Importantly, healthcare professionals now have even more reason to help patients identify changing symptoms and uncover early signs of progression."

Novartis is committed to bringing Mayzent to patients worldwide, and additional regulatory filings are currently underway with other health authorities outside the US. Regulatory action for Mayzent in the European Union is anticipated in late 2019, with additional regulatory action anticipated in Switzerland, Japan, Australia and Canada this year.

*Clinically isolated syndrome (CIS) is defined as a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination in the central nervous system[6].

**Time of availability may vary as healthcare providers integrate Mayzent into their practices.

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

FDA Approves Mayzent (siponimod) for Secondary Progressive Multiple Sclerosis

U.S. FDA Grants Priority Review for Fedratinib New Drug Application in Myelofibrosis

Celgene Corporation (NASDAQ:CELG)   announced the U.S. Food and Drug Administration (FDA) has accepted the company’s New Drug Application (NDA) for fedratinib and granted a Priority Review. Fedratinib is a highly selective JAK2 inhibitor intended for the treatment of patients with myelofibrosis, a serious bone marrow disorder that disrupts the body’s normal production of blood cells.1 Under the Prescription Drug User Fee Act, the FDA has set its action date as Sept. 3, 2019.

  

“The acceptance of the NDA and granting of Priority Review for fedratinib represent the first potential new treatment option after many years for patients affected by myelofibrosis.” said Jay Backstrom, M.D., Chief Medical Officer for Celgene. “Patients with myelofibrosis, including the number who are ineligible for or failed existing therapy continues to increase, representing a well-defined unmet medical need. We believe fedratinib can play an important role in the treatment of myelofibrosis and we look forward to working with the FDA as the review process advances.”

The NDA for fedratinib is based on results from a randomized, placebo-controlled, phase 3 trial (JAKARTA)in patients with primary or secondary myelofibrosis, as well as a single-arm, open-label phase 2 trial (JAKARTA2) in patients with primary or secondary myelofibrosis previously exposed to ruxolitinib, the only FDA-approved treatment for the disease. Results of these two trials have been previously published in peer-reviewed journals. The FDA has also provided fedratinib Orphan Drug designation for the treatment of secondary and primary myelofibrosis.

Celgene also plans to evaluate fedratinib in combination with luspatercept.

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

https://pubchem.ncbi.nlm.nih.gov/compound/Tg-101348#section=Structures

U.S. FDA Grants Priority Review for Fedratinib New Drug Application in Myelofibrosis

TB Medicine Pretomanid Enters Regulatory Review Process in the United States

 TB Alliance’s new drug application (NDA) for the novel tuberculosis (TB) drug candidate pretomanid has been accepted for review by the United States Food and Drug Administration (FDA). The application is for the use of pretomanid as part of a new regimen, in combination with bedaquiline and linezolid, for the treatment of extensively drug-resistant (XDR) TB, treatment intolerant multidrug-resistant (MDR) TB, and treatment non-responsive MDR-TB.

The NDA for pretomanid has been granted Priority Review by FDA. The Prescription Drug User Fee Act (PDUFA) action date for an FDA decision is in third quarter 2019.

TB Alliance will work with manufacturing partners to ensure that pretomanid, if approved for use in the BPaL regimen, will be accessible to those who need it.

About Pretomanid and the BPaL Regimen

Pretomanid is a new chemical entity and a member of a class of compounds known as nitroimidazooxazines. It has been studied in 20 clinical trials alone or in combination with other anti-TB drugs. Since TB Alliance began development of pretomanid in 2002, it has been administered in a clinical trial setting to more than 1,200 people in 14 countries.

The BPaL regimen (comprised of bedaquiline, pretomanid and linezolid) was first studied clinically in the Phase 3 Nix-TB trial. Nix-TB participants with XDR-TB and treatment intolerant or nonresponsive MDR-TB were enrolled for treatment with the BPaL regimen for six months, extendable to nine months, with the intent to cure. Nix-TB is an open label, single arm trial. According to a modified intention-to-treat analysis of interim results on the first 75 participants presented at the 2018 Union World Conference on Lung Health, 89% of the trial participants had a favorable outcome with their clinical infection resolved and sputum cultures negative for TB after six months of treatment and six months of post-treatment follow-up.

https://www.tballiance.org/portfolio/compound/pretomanid

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

https://www.drugbank.ca/drugs/DB05154

TB Medicine Pretomanid Enters Regulatory Review Process in the United States

Intellipharmaceutics Announces Resubmission of New Drug Application to the U.S. FDA for its Oxycodone ER

 In continuation of my update on Oxycodone ER

ntellipharmaceutics International Inc. (NASDAQ: IPCI, TSX: IPCI) ("Intellipharmaceutics" or the "Company"), a pharmaceutical company specializing in the research, development and manufacture of novel and generic controlled-release and targeted-release oral solid dosage drugs,  announced that it has resubmitted its New Drug Application ("NDA") to the U.S. Food and Drug Administration ("FDA") for its Oxycodone ER product candidate.

The Company's NDA for an abuse-deterrent version of Oxycodone ER was initially accepted for filing by the FDA in February 2017. Intellipharmaceutics resubmitted the NDA in response to a Complete Response Letter ("CRL") received from the FDA, which provided certain recommendations and requests for information. The FDA granted us an extension to February 28, 2019 to resubmit our NDA under section 505(b)(2) of the U.S. Federal Food, Drug and Cosmetic Act and the Company has now met this deadline.

There can be no assurance that Intellipharmaceutics will not be required to conduct further studies for Oxycodone ER, that the FDA will approve any of the Company's requested abuse-deterrent label claims or that the FDA will ultimately approve the NDA for the sale of Oxycodone ER in the U.S. market, or that it will ever be successfully commercialized.

About Intellipharmaceutics

Intellipharmaceutics International Inc. is a pharmaceutical company specializing in the research, development and manufacture of novel and generic controlled-release and targeted-release oral solid dosage drugs. The Company's patented Hypermatrix™ technology is a multidimensional controlled-release drug delivery platform that can be applied to a wide range of existing and new pharmaceuticals. Intellipharmaceutics has developed several drug delivery systems based on this technology platform, with a pipeline of products (some of which have received FDA approval) in various stages of development. The Company has ANDA and NDA 505(b)(2) drug product candidates in its development pipeline. These include the Company's abuse-deterrent oxycodone hydrochloride extended release formulation ("Oxycodone ER") based on its proprietary nPODDDS™ novel Point Of Divergence Drug Delivery System (for which an NDA has been filed with the FDA), and Regabatin™ XR (pregabalin extended-release capsules).

Cautionary Statement Regarding Forward-Looking Information

Certain statements in this document constitute "forward-looking statements" within the meaning of the United States Private Securities Litigation Reform Act of 1995 and/or "forward-looking information" under the Securities Act (Ontario). These statements include, without limitation, statements expressed or implied regarding our expectations regarding our plans, goals and milestones, status of developments or expenditures relating to our business, plans to fund our current activities, and statements concerning our partnering activities, health regulatory submissions, strategy, future operations, future financial position, future sales, revenues and profitability, projected costs and market penetration and risks or uncertainties related to our ability to comply with the Nasdaq and TSX continued listing standards and our ability to develop and implement a plan of compliance with the Nasdaq continued listing standards acceptable to a Nasdaq Panel. In some cases, you can identify forward-looking statements by terminology such as "appear", "unlikely", "target", "may", "will", "should", "expects", "plans", "plans to", "anticipates", "believes", "estimates", "predicts", "confident", "prospects", "potential", "continue", "intends", "look forward", "could", "would", "projected", "goals", "set to", "seeking" or the negative of such terms or other comparable terminology. We made a number of assumptions in the preparation of our forward-looking statements. You should not place undue reliance on our forward-looking statements, which are subject to a multitude of known and unknown risks and uncertainties that could cause actual results, future circumstances or events to differ materially from those stated in or implied by the forward-looking statements. Risks and uncertainties relating to us and our business can be found in the "Risk Factors" section of our latest annual information form, our latest Form 20-F, and our latest Form F-1 and Form F-3 (including any documents forming a part thereof or incorporated by reference therein), as amended, as well as in our reports, public disclosure documents and other filings with the securities commissions and other regulatory bodies in Canada and the U.S., which are available on www.sedar.com and www.sec.gov. The forward-looking statements reflect our current views with respect to future events and are based on what we believe are reasonable assumptions as of the date of this document and we disclaim any intention and have no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

https://www.drugbank.ca/drugs/DB00497

Intellipharmaceutics Announces Resubmission of New Drug Application to the U.S. FDA for its Oxycodone ER

Allergan Announces FDA Acceptance of New Drug Application for Ubrogepant for the Acute Treatment of Migraine

   Allergan plc (NYSE: AGN)  announced that the U.S. Food and Drug Administration (FDA) has accepted the company's New Drug Application (NDA) for ubrogepant for the acute treatment of migraine in adults. The NDA filing is based on the successful completion of four clinical trials – two pivotal studies, ACHIEVE I and ACHIEVE II, which demonstrated the efficacy, safety and tolerability of ubrogepant, as well as two additional safety studies. A 10-month review period has been assigned with the Prescription Drug User Fee Act (PDUFA) in the fourth quarter of 2019.

"Following the acceptance and expected review of this NDA, we anticipate ubrogepant to be the first approved oral CGRP receptor antagonist for the acute treatment of migraine, and may be used in conjunction with other available migraine treatments," said David Nicholson, Chief Research and Development Officer, Allergan. "As a leader in Chronic Migraine research for more than 20 years, Allergan looks to provide options for patients who need new acute and preventative treatments for migraine. In addition to ubrogepant, we are continuing to advance the Phase 3 clinical program for atogepant, the company's second orally-administered investigational CGRP receptor antagonist specifically for migraine prevention."

In the four clinical studies (ACHIEVE I, ACHIEVE II, UBR-MD-04 and 3110-105-002) supporting the NDA, ubrogepant demonstrated efficacy, safety and tolerability in the acute treatment of migraine among a broad patient population, including those who had an insufficient response to a triptan or those patients in whom triptans were contraindicated, as well as in patients who had moderate to severe CV risk profile. Following are topline results from the key clinical studies:

Phase 3 Clinical Trials (ACHIEVE I & ACHIEVE II)

The two pivotal Phase 3 clinical trials demonstrated the efficacy, safety and tolerability of orally administered ubrogepant (ACHIEVE I at 50 mg and 100 mg; and ACHIEVE II at 25 mg and 50 mg) compared to placebo to treat a single migraine attack in adults.

• The 50 mg and 100 mg doses met the studies' co-primary endpoints, demonstrating a statistically significant greater percentage of ubrogepant patients achieving pain freedom and absence of most bothersome symptom at two hours after the initial dose as compared to placebo patients; there was continued separation from placebo up to 48 hours.
• The 50 mg and 100 mg doses also met key secondary endpoints, demonstrating a statistically significant greater percentage of ubrogepant patients achieving pain relief at two hours after the initial dose compared to placebo patients.

Additional Safety Studies (UBR-MD-04 & 3110-105-002)

Study UBR-MD-04: Phase 3, multicenter, randomized, 52-week open-label extension trial in which adults with migraine were randomized 1:1:1 to usual care, ubrogepant 50 mg, or ubrogepant 100 mg to assess long-term safety and tolerability.

• Intermittent use of ubrogepant 50 mg or 100 mg for the acute treatment of migraine attacks over one year was well-tolerated. The three most frequently reported adverse events were nasopharyngitis, upper respiratory tract infection and sinusitis.

Study 3110-105-002: Phase 1, multicenter, double-blind, parallel-group trial evaluated the safety and tolerability of ubrogepant 100 mg, focusing on hepatic safety in healthy participants administered high frequency intermittent  dosing (2 days of ubrogepant 100 mg followed by 2 days of placebo for 8 consecutive weeks).

• Ubrogepant 100 mg was well-tolerated following frequent dosing and was not associated with persistent increases in ALT/AST compared to placebo, supporting liver safety.

"Despite its prevalence and burden, migraine remains an undertreated disease, with many patients continuing to seek additional treatment options from their physicians," said Dr. Jessica Ailani, a neurologist and Director of the Medstar Georgetown Headache Center. "If approved, ubrogepant, the first innovation in the acute treatment of migraine in over 25 years, will be used across the entire spectrum of the disease (from episodic to chronic) helping patients achieve relief in the moments when they most demand it."

About Ubrogepant

Ubrogepant is a novel, highly potent, orally-administered CGRP receptor antagonist in development for the acute treatment of migraine. CGRP and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology. CGRP receptor antagonism is a novel mechanism of action for the acute treatment of migraine that clearly differs from the mechanisms of currently available triptans (serotonin 1B/1D agonists), opioids and ergots.

https://pubchem.ncbi.nlm.nih.gov/compound/Ubrogepant

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

Allergan Announces FDA Acceptance of New Drug Application for Ubrogepant for the Acute Treatment of Migraine

Karyopharm Announces FDA Extension of Review Period for Selinexor New Drug Application

  

Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a clinical-stage pharmaceutical company,  announced that the U.S. Food and Drug Administration (FDA) has extended the Prescription Drug User Fee Act (PDUFA) action date for the New Drug Application (NDA) for selinexor. The NDA, which is currently under Priority Review by the FDA, is seeking accelerated approval for selinexor in combination with dexamethasone for the treatment of patients with relapsed refractory multiple myeloma who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor (PI), one immunomodulatory agent (IMiD), and one anti-CD38 monoclonal antibody. The previously disclosed April 6, 2019 PDUFA date has been extended by three months to July 6, 2019.

On February 26, 2019, the FDA'sOncologic Drugs Advisory Committee (ODAC) met to discuss the selinexor NDA and voted 8 to 5 recommending that the FDA wait for the results from Karyopharm's randomized, open-label, Phase 3 BOSTON study evaluating selinexor in patients with relapsed or refractory multiple myeloma, before making a final decision regarding approval.  Although the FDA considers the recommendation of this panel, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are non-binding.

Following the ODAC meeting, at the FDA's request,  Karyopharm submitted additional, existing clinical information as an amendment to the NDA, which allowed the FDA to extend the PDUFA action date by three months. "We look forward to the continued collaboration with FDA in trying to meet the needs of patients with relapsed refractory multiple myeloma," said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm.

About Selinexor

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. In 2018, Karyopharm reported positive data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with triple class refractory multiple myeloma who have been previously exposed to all five of the most commonly prescribed anti-myeloma therapies currently available. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm's New Drug Application (NDA) has been accepted for filing and granted Priority Review by the FDA, and oral selinexor is currently under review by the FDA as a possible new treatment for patients with triple class refractory multiple myeloma. The Company has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval and was granted accelerated assessment. Selinexor is also being studied in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In 2018, Karyopharm reported positive top-line results from the Phase 2b SADAL study evaluating selinexor in patients with relapsed or refractory DLBCL after at least two prior multi-agent therapies and who are ineligible for transplantation, including high dose chemotherapy with stem cell rescue. Selinexor has received Fast Track designation from the FDA for the patient population evaluated in the SADAL study.  Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade® (bortezomib) and low-dose dexamethasone (BOSTON), as a potential backbone therapy in combination with approved therapies (STOMP), in liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm's clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

https://pubchem.ncbi.nlm.nih.gov/compound/Selinexor#section=2D-Structure

Karyopharm Announces FDA Extension of Review Period for Selinexor New Drug Application

FDA Issues Complete Response Letter for Zynquista (sotagliflozin)

In continuation of my update on Zynquista (sotagliflozin)

 The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding the New Drug Application for investigational Zynquista (sotagliflozin)*, a dual SGLT1 and SGLT2 inhibitor for the treatment of adults with type 1 diabetes in combination with insulin.

A CRL is a communication from the FDA that informs companies that an application cannot be approved in its present form.

Sanofi and Lexicon will work closely with the FDA to determine the appropriate next steps.

About Lexicon Pharmaceuticals

Lexicon (NASDAQ: LXRX) is a fully integrated biopharmaceutical company that is applying a unique approach to gene science based on Nobel Prize-winning technology to discover and develop precise medicines for patients with serious, chronic conditions. Through its Genome5000™ program, Lexicon scientists have studied the role and function of nearly 5,000 genes over the last 20 years and have identified more than 100 protein targets with significant therapeutic potential in a range of diseases. Through the precise targeting of these proteins, Lexicon is pioneering the discovery and development of innovative medicines to safely and effectively treat disease. In addition to its first commercial product, XERMELO® (telotristat ethyl), Lexicon has a pipeline of promising drug candidates in clinical and pre-clinical development in diabetes and metabolism and neuropathic pain. For additional information please visit www.lexpharma.com.

*Sotagliflozin is an investigational drug and is under regulatory review by the European Medicines Agency (EMA) and U.S. Food and Drug Administration (FDA). The EMA and FDA have conditionally accepted Zynquista™ as the trade name for sotagliflozin.

https://pubchem.ncbi.nlm.nih.gov/compound/lx-4211#section=Structures

FDA Approves Adhansia XR (methylphenidate hydrochloride) Extended-Release Capsules for the Treatment of ADHD

In continuation of my update on methylphenidate

Adlon Therapeutics L.P., a subsidiary of Purdue Pharma L.P., announced that the U.S. Food and Drug Administration (FDA) approved Adhansia XR (methylphenidate hydrochloride) extended-release capsules CII, a central nervous system (CNS) stimulant, for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients six years and older. In a simulated Adult Workplace Environment (AWE) study, Adhansia XR demonstrated statistically significant improvement over placebo at 1, 2, 5, 8, 11, and 16 hours post-dose, but not at hour 14 post-dose.1

“Methylphenidate medications, when used as prescribed and in conjunction with behavioral therapy and lifestyle interventions, are one of the preferred first-line treatments for certain patients diagnosed with ADHD,” said Marcelo Bigal, MD, PhD, chief medical officer, Purdue Pharma, and general manager, Adlon Therapeutics. “We are pleased to receive FDA approval for Adhansia XR, a new option for appropriate patients with ADHD who may benefit from a treatment with efficacy demonstrated at one hour and 16 hours post-dose in adults, and we look forward to making it available later this year.”

The Full Prescribing Information for Adhansia XR contains a boxed warning for abuse and dependence. CNS stimulants, including Adhansia XR, other methylphenidate-containing products, and amphetamines have a high potential for abuse and dependence. Healthcare professionals should assess the risk of abuse prior to prescribing Adhansia XR and monitor for signs of abuse and dependence while patients are on therapy.

“Some of my patients with ADHD, especially those who are balancing school or work and participating in social or civic activities, require the ability to sustain attention throughout the day,” said Andrew J. Cutler, MD, chief medical officer, Meridien Research, and an investigator on Adhansia XR clinical studies. “The approval of Adhansia XR offers a methylphenidate treatment option with a longer duration of efficacy, which may be appropriate for these patients.”

Adhansia XR is not appropriate for all patients, and healthcare professionals should work with their patients to determine the most appropriate treatment option. Additionally, Adhansia XR is contraindicated in patients with a known hypersensitivity to methylphenidate or product components, as well as patients receiving concurrent treatment with a monoamine oxidase inhibitor (MAOI) or who have used an MAOI within the preceding 14 days.

The Full Prescribing Information for Adhansia XR, including Boxed Warning, is available at this link. Additionally, please see Important Safety Information for Adhansia XR below, including the Boxed Warning, Contraindications, Warnings and Precautions including the potential for abuse and dependence, serious cardiovascular events, blood pressure and heart rate increases, psychiatric adverse reactions, priapism, peripheral vasculopathy, long-term suppression of growth, allergic-type reactions, and Adverse Reactions.

“ADHD affects a significant number of adolescents and adults and, when not optimally treated, can negatively impact various aspects of their lives. A subset of these patients experience impairment throughout the day. While Adhansia XR is not appropriate for all patients, a methylphenidate medication available in a single daily dose that, in adults, demonstrated efficacy at one hour and at 16 hours post-dose, has the potential to address the needs of certain individuals with ADHD,” said Craig Landau, MD, president and CEO, Purdue Pharma. “We are committed to providing information on safe prescribing practices for this medication and initiatives to support the responsible use, storage, and disposal of all medications in this class."

The FDA approval of Adhansia XR was based on four clinical studies evaluating the efficacy and safety of Adhansia XR in patients who met DSM-5 criteria for ADHD. Eight hundred and eighty-three (883) patients were exposed to Adhansia XR during 1- to 4-week long, controlled treatment periods (434 adult patients and 449 pediatric patients [156 (6 to 12 years); 293 (12 to 17 years)] from two clinical studies in adults, one analog classroom trial over a 13-hour study day in pediatric patients ages 6 to 12 years, and one safety and efficacy study in pediatric patients ages 12 to 17 years). The safety data for adult patients are based on two randomized, double-blind, placebo-controlled studies in doses of 25 mg to 100 mg per day. The safety data for pediatric patients (6 to 17 years) are based on randomized, double-blind, placebo-controlled studies in doses of 25 mg to 85 mg per day.

A double-blind, randomized, placebo-controlled crossover AWE study evaluated Adhansia XR in adult patients with ADHD. Efficacy assessments were conducted at pre-dose and 1, 2, 5, 8, 11, 14, and 16 hours post-dose. The primary endpoint was the mean Permanent Measure of Performance Total scores (PERMP-T), averaged across all time points compared to placebo. PERMP-T, an objective, validated skill-adjusted math test, is the combined score obtained by adding PERMP-A (number of math problems attempted) and PERMP-C (number of math problems answered correctly).

While receiving Adhansia XR, adults achieved statistically significant improvement over placebo, achieving greater mean PERMP-T scores averaged across all time points on the AWE days (post-dose score of 281.3 vs. 254.5; difference of 26.80, 95% CI [15.19, 38.41]). The secondary efficacy endpoints were onset and duration of clinical effect, as assessed by the treatment difference in PERMP-T scores at post-dose time points. Adhansia XR demonstrated statistically significant improvement over placebo at 1, 2, 5, 8, 11, and 16 hours post-dose, but not at hour 14 post-dose.

In this study, 10% of Adhansia XR-treated patients discontinued due to adverse reactions compared to 0% of placebo-treated patients. The following adverse reactions led to discontinuation at a frequency of 2% of Adhansia XR-treated patients: nausea, bronchitis, viral gastroenteritis, viral infection, increased blood pressure, and hypomania.

Sudden death, stroke and myocardial infarction have occurred in patients treated with CNS stimulants at recommended doses. Additional information about serious cardiovascular risks can be found in the Important Safety Information section below.

Adhansia XR will be available in six capsule strengths (25, 35, 45, 55, 70, and 85 mg), allowing for flexible dosing. The recommended starting dose of Adhansia XR for patients six years or older is 25 mg once daily. Healthcare professionals should titrate the dose in increments of 10 mg to 15 mg at intervals of no less than five days. Adhansia XR should be taken orally once daily in the morning, with or without food. Capsules may be taken whole or, for patients who have difficulty swallowing, capsules may be opened and the entire contents sprinkled onto a tablespoon of applesauce or yogurt. The entire mixture should be consumed without crushing or chewing, immediately or within 10 minutes. If the mixture is not consumed within 10 minutes after mixing, it should be discarded and not stored. The dose of a single capsule should not be divided and patients should not take anything less than one capsule per day. In the event of a missed dose, patients should not take their medication later in the day.

Prior to initiating treatment with Adhansia XR, healthcare professionals should also assess for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam). Healthcare professionals should assess the risk of abuse prior to prescribing Adhansia XR and monitor for signs of abuse and dependence while patients are on therapy. After prescribing and while patients are on therapy, healthcare professionals should maintain careful prescription records, educate patients and their families about abuse and proper storage and disposal of CNS stimulants, and periodically re-evaluate the need for Adhansia XR use.

Dosages above 85 mg daily in adults and 70 mg and above daily in pediatric patients are associated with disproportionate increases in the incidence of certain adverse reactions. If paradoxical aggravation of symptoms or other adverse reactions occur, healthcare professionals should reduce the dosage, or, if necessary, discontinue treatment with Adhansia XR. Treatment with Adhansia XR should also be periodically discontinued to assess the patient's condition. If improvement is not observed in a patient after appropriate dosage adjustment over a one-month period, healthcare providers should discontinue treatment with Adhansia XR.1 Healthcare professionals should refer to the Full Prescribing Information for additional Dosage and Administration information.

Prescription stimulants, which include methylphenidate, the active ingredient in Adhansia XR, are federally controlled substances (CII) and have a high potential for abuse and dependence.1,2 The selling or giving away of methylphenidate medications may harm others or lead to death, and is against the law. It is important for healthcare professionals to ask patients if they or a family member have ever misused prescription medicines or abused alcohol or street drugs. Patients should be counseled that they should not give Adhansia XR to anyone else, and to keep methylphenidate medications in a safe place, such as a locked cabinet, to help prevent accidental exposure, diversion, and abuse.  They should also be advised to dispose of remaining, unused, or expired Adhansia XR by a medicine take-back program at authorized collection sites such as pharmacies or law enforcement locations, if available. If no take-back program or authorized collector is available, patients should mix Adhansia XR with an undesirable, nontoxic substance to make it less appealing to children and pets, place the mixture in a container such as a sealed plastic bag, and discard of it in the household trash.1 Patients should be encouraged to read the Medication Guide that accompanies their stimulant prescription, which contains the most important FDA-approved information that a patient should know about the medication

REf: https://en.wikipedia.org/wiki/Methylphenidate

FDA Approves Jatenzo (testosterone undecanoate) for Certain Forms of Hypogonadism

 The U.S. Food and Drug Administration  approved Jatenzo (testosterone undecanoate), an oral testosterone capsule to treat men with certain forms of hypogonadism. These men have low testosterone levels due to specific medical conditions, such as genetic disorders like Klinefelter syndrome or tumors that have damaged the pituitary gland. Jatenzo should not be used to treat men with “age-related hypogonadism,” in which testosterone levels decline due to aging, even if these men have symptoms that appear to be related to low testosterone. Jatenzo’s benefits do not outweigh its risks for that use.

“Jatenzo’s oral route of administration provides an important addition to current treatment options available for men with certain hypogonadal conditions who up until now have most commonly been treated with testosterone products that are applied to the skin or injected,” said Hylton V. Joffe, M.D, M.M.Sc., director of the Division of Bone, Reproductive and Urologic Products in the FDA’s Center for Drug Evaluation and Research. “But it’s important to emphasize that this drug should not, like other testosterone treatments, be used to treat older men with ‘age-related hypogonadism.’ The benefits of testosterone therapy, including Jatenzo, have not been established for this use, and Jatenzo’s effects on raising blood pressure can increase the risks of heart attack, stroke and cardiovascular death in this population.”

The efficacy of Jatenzo was demonstrated in a four-month clinical trial involving 166 men with hypogonadism. Study participants initially were given Jatenzo at a dose of 237 mg twice per day, and the dose was adjusted downward or upward to a maximum of 396 mg twice per day on the basis of testosterone levels. Eighty-seven percent of Jatenzo-treated men achieved an average testosterone level within the normal range, which was the primary study endpoint.

Jatenzo contains a boxed warning on its labeling stating that the drug can cause blood pressure to rise, increasing the risk of heart attack, stroke and cardiovascular death. Health care providers should consider a patient’s individual heart disease risks and ensure that blood pressure is adequately controlled before prescribing Jatenzo; they should also periodically monitor patient blood pressure during treatment. Jatenzo is currently one of two testosterone products that have this boxed warning. The FDA is requiring all testosterone product manufacturers to conduct blood pressure postmarketing trials to more clearly address whether these products increase blood pressure.

Common side effects, occurring in more than 2 percent of patients in the Jatenzo clinical trial, included headache, an increase in hematocrit (red blood cell count), a decrease in high-density lipoprotein cholesterol (“good” cholesterol), high blood pressure and nausea. An increase in prostate specific antigen (PSA) was also observed. Patients should have their hematocrit, cholesterol and PSA monitored regularly to check for changes. Those with benign prostate hyperplasia should be monitored for worsening of symptoms.

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

FDA Approves Jatenzo (testosterone undecanoate) for Certain Forms of Hypogonadism

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 Spravato (esketamine) Nasal Spray for Treatment-Resistant Depression

  In continuation of my update on esketamine

The U.S. Food and Drug Administration   approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression). Because of the risk of serious adverse outcomes resulting from sedation and dissociation caused by Spravato administration, and the potential for abuse and misuse of the drug, it is only available through a restricted distribution system, under a Risk Evaluation and Mitigation Strategy (REMS).

"There has been a long-standing need for additional effective treatments for treatment-resistant depression, a serious and life-threatening condition," said Tiffany Farchione, M.D., acting director of the Division of Psychiatry Products in the FDA's Center for Drug Evaluation and Research. "Controlled clinical trials that studied the safety and efficacy of this drug, along with careful review through the FDA’s drug approval process including a robust discussion with our external advisory committees, were important to our decision to approve this treatment. Because of safey concerns, the drug will only be available through a restricted distribution system and it must be administered in a certified medical office where the health care provider can monitor the patient."

Patients with major depressive disorder who, despite trying at least two antidepressant treatments given at adequate doses for an adequate duration in the current episode, have not responded to treatment are considered to have treatment-resistant depression.

The Spravato labeling contains a Boxed Warning that cautions that patients are at risk for sedation and difficulty with attention, judgment and thinking (dissociation), abuse and misuse, and suicidal thoughts and behaviors after administration of the drug. Because of the risk of sedation and dissociation, patients must be monitored by a health care provider for at least two hours after receiving their Spravato dose. The REMS requires the prescriber and the patient to both sign a Patient Enrollment Form that clearly states that the patient understands they should make arrangements to safely leave the health care setting to get home and that the patient should not drive or use heavy machinery for the rest of the day on which they receved the drug. Additionally, Spravato must be dispensed with a patient Medication Guide that outlines the drug’s uses and risks.

The patient self-administers Spravato nasal spray under the supervision of a health care provider in a certified doctor’s office or clinic, and the spray cannot be taken home. The health care provider will instruct the patient on how to operate the nasal spray device. During and after each use of the nasal spray device, the health care provider will check the patient and determine when the patient is ready to leave.

The efficacy of Spravato was evaluated in three short-term (four-week) clinical trials and one longer-term maintenance-of-effect trial. In the three short-term studies, patients were randomized to receive Spravato or a placebo nasal spray. In light of the serious nature of treatment-resistant depresison and the need for patients to receive some form of treatment, all patients in these studies started a new oral antidepressant at the time of randomization and the new antidepressant was continued throughout the trials. The primary efficacy measure was the change from baseline on a scale used to assess the severity of depressive symptoms. In one of the short-term studies, Spravato nasal spray demonstrated statistically significant effect compared to placebo on the severity of depression, and some effect was seen within two days. The two other short-term trials did not meet the pre-specified statistical tests for demonstrating effectiveness. In the longer-term maintenance-of-effect trial, patients in stable remission or with stable response who continued treatment with Spravato plus an oral antidepressant experienced a statistically significantly longer time to relapse of depressive symptoms than patients on placebo nasal spray plus an oral antidepressant.

The most common side effects experienced by patients treated with Spravato in the clinical trials were disassociation, dizziness, nausea, sedation, vertigo, decreased feeling or sensitivity (hypoesthesia), anxiety, lethargy, increased blood pressure, vomiting and feeling drunk.

Patients with unstable or poorly controlled hypertension or pre-existing aneurysmal vascular disorders may be at increased risk for adverse cardiovascular or cerebrovascular effects. Spravato may impair attention, judgment, thinking, reaction speed and motor skills. Patients should not drive or operate machinery until the next day after a restful sleep. Spravato may cause fetal harm and women of reproductive potential should consider pregnancy planning and prevention; women should not breastfeed while being treated.

Esketamine is the s-enantiomer of ketamine. Ketamine is a mixture of two enantiomers (mirror image molecules). This is the first FDA approval of esketamine for any use. The FDA approved ketamine (Ketalar) in 1970.

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

FDA Approves Spravato (esketamine) Nasal Spray for Treatment-Resistant Depression

FDA Approves Rocklatan (netarsudil and latanoprost ophthalmic solution) for the Reduction of Intraocular Pressure in Open-Angle Glaucoma or Ocular Hypertension

In continuation of my update on latanoprost 

Aerie Pharmaceuticals, Inc. (NASDAQ:AERI) (Aerie or the Company), an ophthalmic pharmaceutical company focused on the discovery, development and commercialization of first-in-class therapies for the treatment of patients with open-angle glaucoma, retinal diseases and other diseases of the eye,   announced that the U.S. Food and Drug Administration (FDA) has approved Rocklatan (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% to reduce elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. 

Rocklatan is a once-daily eye drop that is a fixed-dose combination of latanoprost, the most widely-prescribed prostaglandin analog (PGA), and netarsudil, the active ingredient in Rhopressa (netarsudil ophthalmic solution) 0.02%, a first-in-class Rho kinase (ROCK) inhibitor specifically designed to target the trabecular meshwork (the eye’s principal drainage pathway). The diseased trabecular meshwork is considered to be the main cause of elevated IOP in open-angle glaucoma and ocular hypertension. Rhopressa® works by restoring outflow through the trabecular meshwork, while latanoprost increases fluid outflow through a secondary mechanism known as the uveoscleral pathway.

Aerie launched Rhopressa® in the United States in April 2018. The Company plans to launch Rocklatan™ in the United States in the second quarter of 2019.

“We are in the unique position of receiving FDA approval on a second glaucoma treatment less than a year from the U.S. launch of Rhopressa®,” said Vicente Anido, Jr., Ph.D., chairman and chief executive officer at Aerie. “Together, Rocklatan™ and Rhopressa® give us a broad therapeutic franchise, based on our ROCK inhibitor netarsudil, that addresses many of the needs of clinicians and patients in a wide variety of treatment settings. Our existing salesforce, which has been calling on U.S. eye-care professionals since last May, is very well positioned to introduce Rocklatan™ to these doctors and help them understand the clinical utility of both products in the care of their patients with glaucoma. We have also been working diligently on securing favorable reimbursement for our products, with Rhopressa® now enjoying broad commercial and Medicare Part D coverage, and Rocklatan™ already under review by major payers.”

The FDA approval of Rocklatan is based on data from two Phase 3 registration trials, MERCURY 1 and MERCURY 2. In these studies, Rocklatan™ achieved its primary 90-day efficacy endpoint as well as positive 12-month safety and efficacy results, demonstrating statistically superior IOP reduction over latanoprost and netarsudil at every measured time point. More than 60% of patients taking Rocklatan™ in the two MERCURY studies achieved an IOP reduction of 30% or more, a frequency that was nearly twice that achieved by participants taking latanoprost alone. Rocklatan™ also helped more patients get to low target pressures. Nearly twice as many patients taking Rocklatan™ reached 16 mmHg or lower and nearly three times as many reached 14 mmHg or lower compared to latanoprost.

In the two MERCURY studies, Rocklatan treatment was associated with generally mild and tolerable ocular adverse events, with minimal systemic side effects. The most common ocular adverse event in controlled clinical studies with Rocklatan™ was conjunctival hyperemia. Ninety percent of patients who experienced hyperemia reported it as mild and 5% discontinued because of it. Other common ocular adverse effects reported in the studies include instillation site pain, corneal verticillata and conjunctival hemorrhage.

About Rocklatan

Indications and Usage

Rocklatan (netarsudil and latanoprost ophthalmic solution) 0.02%/0.005% is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

Select Important Safety Information

Although not observed in the two MERCURY studies, latanoprost has been reported to cause changes to pigmented tissues, including pigmentation of the iris, periorbital tissue (eyelid) and eyelashes. Iris pigmentation is likely to be permanent. Latanoprost has also been associated with gradual changes to eyelashes including increased length, thickness and number of lashes. These changes are usually reversible.

Ewf https://www.drugbank.ca/drugs/DB00654

https://www.biospace.com/article/fda-approves-aerie-pharma-s-glaucoma-combo-eye-drops/