FDA Approves Exservan (riluzole) Oral Film for the Treatment of Amyotrophic Lateral Sclerosis

In continuation of my update on riluzole

Aquestive Therapeutics, Inc. (NASDAQ: AQST), a specialty pharmaceutical company focused on developing and commercializing differentiated products to solve therapeutic problems,  announced that Exservan (riluzole) Oral Film received early-action approval from the U.S. Food and Drug Administration (FDA) for the treatment of amyotrophic lateral sclerosis (ALS), an orphan disease.

We received full FDA approval for Exservan in advance of our PDUFA action date.  We appreciate the ongoing feedback from the FDA and its early-action approval.  We anticipate that Exservan, via our orally administered PharmFilm® dosage form, will bring meaningful treatment to patients who are diagnosed with ALS and face difficulties swallowing or administering traditional forms of medication,” said Keith J. Kendall, Chief Executive Officer of Aquestive.  “In line with our stated objectives, we licensed this product to Zambon S.p.A. for development and commercialization in the EU.  We are continuing the dialogue with potential licensees for the US commercial rights.”

Exservan (riluzole) Oral Film is now approved for the treatment of ALS, a debilitating and rare disease affecting as many as 30,000 Americans1 and 52,000 Europeans.  Exservan will now fill a critical need in the armamentarium for ALS patients because it can be administered safely and easily, twice daily, without water where many patients have trouble swallowing. Development initiatives conducted by Aquestive have included studies demonstrating Exservan's pharmacokinetic bioequivalence to the reference listed drug, Rilutek®, as well as additional studies to assess patients' ability to swallow Exservan. Exservan received FDA orphan drug designation in January 2018.

https://www.rxlist.com/exservan-drug.htm

FDA Approves RediTrex (methotrexate) for Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, and Psoriasis

In continuation of my update on methotrexate

Cumberland Pharmaceuticals Inc. (NASDAQ: CPIX), a specialty pharmaceutical company, today announced that it has received approval from the U.S. Food and Drug Administration (FDA) for RediTrex, its new line of methotrexate products.

RediTrex (methotrexate) injection is designed for the treatment of adult and pediatric patients with rheumatoid arthritis, as well as adults with psoriasis. The approval of the product came after a number of communications with the FDA and several amendments to the New Drug Application we submitted to the FDA in late 2018.

Methotrexate is approved in the U.S. as both an oral and injectable treatment. While oral formulations are widely available, injectable methotrexate has been shown to result in increased efficacy, greater continuation rates and less discomfort for patients. Cumberland's methotrexate products will provide enhancements and patient benefits over conventional injectable methotrexate products currently available in the U.S.

Cumberland has acquired exclusive U.S. commercial rights to Nordic Group B.V.'s (Nordic) injectable methotrexate line of products. Nordic is a privately-owned European pharmaceutical company with a presence in 17 countries. The company focuses on the development and commercialization of niche hospital and orphan products, aiming to address unmet medical needs. Nordic's methotrexate products are established market leaders in multiple European countries.

"We are delighted by the FDA approval of RediTrex for the United States," said A.J. Kazimi, Chief Executive Officer of Cumberland Pharmaceuticals. "We are looking forward to bringing this important product to the patients seeking an easy-to-use methotrexate injectable."

Cumberland will launch two injectable methotrexate product lines within the U.S., with both product offerings intended for the treatment of active rheumatoid arthritis, juvenile idiopathic arthritis and severe psoriasis.

The injectable U.S. methotrexate market totaled over 670,000 prescriptions last year, with approximately $80 million in overall sales. This methotrexate market has grown at a rate of 72 percent over the previous three years. Cumberland's goal is to achieve a significant share of the injectable methotrexate market over time through the introduction of RediTrex.

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

FDA Approves Nouress (cysteine hydrochloride) Injection for Treating Neonate Patients Requiring Total Parenteral Nutrition (TPN)

Avadel Pharmaceuticals plc (Nasdaq: AVDL) announced that the U.S. Food and Drug Administration (FDA) has approved Nouress (AV001), a cysteine hydrochloride injection, a critical drug for treating neonatal patients requiring total parenteral nutrition (TPN).

In addition, Avadel announced today that the United States Patent and Trademark Office (USPTO) recently issued United States Patent No. 10,493,051 covering cysteine solutions, including the approved Nouress product. This patent is listed in the Orange Book for Nouress and is set to expire in March of 2039. Avadel has additional U.S. patent applications pending for Nouress.

“We are pleased to receive FDA approval for Nouress, which validates our strategy of developing innovative medicines for patients,” said Greg Divis, Chief Executive Officer of Avadel. “Nouress is the fourth FDA approved product in our sterile injectable hospital business. The cash flow generated by this legacy business is supporting the clinical development costs from our lead program, FT218, which is currently expected to announce topline data from the pivotal Phase 3 REST-ON trial in the second quarter of 2020. We believe that as a once-nightly formulated sodium oxybate, FT218, if approved by the FDA, has the potential to take a significant share of the twice-nightly sodium oxybate market, which is currently valued at an estimated annualized rate of $1.7 billion.”

Avadel is currently evaluating the timing and process for a commercial launch of Nouress in the United States. In this regard, a competitor received FDA approval earlier this year for its cysteine hydrochloride injection and more recently was granted a U.S. patent, which Avadel is assessing along with other market factors. 

Due to a historical lack of reliable supply, U.S. markets previously imported cysteine hydrochloride injection from Canada under special FDA rules allowing shortage drugs to be sourced abroad if no domestic supplies are available. With FDA approvals of Nouress and another U.S. company’s cysteine hydrochloride injection earlier this year, Avadel expects the domestic supply of cysteine hydrochloride injection will be sufficient to support the entire U.S. market, which, under FDA regulations, should preclude further import or U.S. marketing of unapproved cysteine hydrochloride injection products.  Under these potential market conditions, the U.S. annual market for cysteine hydrochloride could be greater than $50 million. 

https://pubchem.ncbi.nlm.nih.gov/compound/L-Cysteine-hydrochloride

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

https://www.drugbank.ca/salts/DBSALT001754

FDA Approves Conjupri (levamlodipine maleate) for the Treatment of Hypertension

 The board of directors (the “Board”) of CSPC Pharmaceutical Group Limited (the “Company”, together with its subsidiaries, the “Group”) is pleased to announce that Conjupri® (levoamlodipine maleate) tablets has received marketing approval from the U.S. Food and Drug Administration (FDA) for the treatment of hypertension. Based on our knowledge, this is the first New Drug Application (NDA) ever submitted to the FDA by Chinese pharmaceutical companies, and now granted full approval following a standard review by the FDA.

Levoamlodipine is the purified (S)-amlodipine, the pharmacologically active enantiomer in amlodipine (a racemic mixture of (R)- and (S)-amlodipine), for the treatment of hypertension. Amlodipine is a third-generation calcium channel blocker first developed and marketed by Pfizer as NORVASC® (amlodipine besylate) tablets in 2.5 mg, 5.0 mg, and 10.0 mg in 1992. The approved Conjupri® (levoamlodipine maleate) tablets come in 1.25 mg, 2.5 mg and 5.0 mg.

Levoamlodipine maleate tablets have been marketed by the Group as Xuanning ( 玄寧) in China since 2003. The clinical development of levoamlodipine maleate tablets in the U.S. was based on the safety and efficacy data demonstrated in China and data showing that levoamlodipine has less adverse events than amlodipine.

This NDA approval allows the Group to market Conjupri® in the U.S. and also paves the way for marketing in other parts of the world. As the first levoamlodipine approved by the FDA, Conjupri® is qualified to be the reference standard for drugs with the same active ingredient.

The NDA approval of levoamlodipine maleate tablets in the U.S. is a manifestation of the Group’s commitment to innovation and to bringing the best medicines to patients worldwide.

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

FDA Approves Dayvigo (lemborexant) for the Treatment of Insomnia in Adult Patients

In continuation of my update on lemborexant

Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) today announced that the U.S. Food and Drug Administration (FDA) approved the new drug application for its in-house discovered and developed orexin receptor antagonist Dayvigo (lemborexant). Dayvigo was approved for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance in adults1. In the United States, Dayvigo will be commercially available in 5 mg and 10 mg tablets following scheduling by the U.S. Drug Enforcement Administration (DEA), which is expected to occur within 90 days.

The mechanism of action of lemborexant in the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system plays a role in wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to orexin receptors OX1R and OX2R is thought to suppress wake drive. Lemborexant binds to orexin receptors OX1R and OX2R and acts as a competitive antagonist with stronger inhibition effect to OX2R*.

The approval was based on the results of a clinical development program that included two pivotal Phase III studies (SUNRISE 2 and SUNRISE 1), which evaluated Dayvigo versus comparators for up to one month and Dayvigo versus placebo for six-months, respectively, in a total of about 2,000 adult patients with insomnia. From these studies results, Dayvigo demonstrated statistically significant superiorities on sleep onset and sleep maintenance compared to placebo in both subjective and objective evaluations.

Across SUNRISE 2 and SUNRISE 1, Dayvigo was not associated with rebound insomnia following treatment discontinuation, and there was no evidence of withdrawal effects following Dayvigo discontinuation at either dose. In addition, the development program included multiple safety studies evaluating effects on postural stability, cognition, driving performance and respiratory safety.

• SUNRISE 2 was a long-term (six month), randomized, double-blind, placebo-controlled, multi-center, trial in adult patients age 18 or older who met DSM-5** criteria for insomnia disorder. Patients were randomized to placebo (n=325), Dayvigo 5 mg (n=323), or Dayvigo 10 mg (n=323) once nightly. The primary efficacy endpoint was the mean change from baseline to end of treatment at six months for patient-reported (subjective) sleep onset latency (sSOL), defined as the estimated minutes from the time that the subject attempted to sleep until falling asleep. Pre-specified secondary efficacy endpoints were change from baseline to end of treatment at six months for patient reported sleep efficiency (sSE; defined as the proportion of time spent asleep during time in bed) and subjective sleep onset and sleep maintenance (sWASO; defined as the minutes of wake from the onset of persistent sleep until lights on). The primary and pre-specified secondary efficacy endpoints were measured using a Sleep Diary. In SUNRISE 2, Dayvigo 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, sSOL, compared to placebo. Dayvigo 5 mg and 10 mg also showed statistically significant superiority in sSE and sWASO.1
• SUNRISE 1 was a short-term (one month), randomized, double-blind, placebo- and active-controlled, multi-center, parallel-group clinical trial in adult female subjects age 55 and older and male subjects 65 years and older who met DSM-5 criteria for insomnia disorder. Patients were randomized to placebo (n=208), Dayvigo 5 mg (n=266) or 10 mg (n=269) or active comparator (n=263) once nightly. The primary efficacy endpoint was the mean change in latency to persistent sleep (LPS; defined as the number of minutes from lights off to the first 10 consecutive minutes of non-wakefulness) from baseline to end of treatment (day 29/30), as measured by overnight polysomnography (PSG) monitoring. The pre-specified secondary efficacy endpoints in SUNRISE 1 were the mean change from baseline to end of treatment (day 29/30) in sleep efficiency (SE) and wake after sleep onset (WASO) measured by PSG. In SUNRISE 1, Dayvigo 5 mg and 10 mg demonstrated statistically significant superiority on the primary efficacy measure, LPS, compared to placebo. Dayvigo 5 mg and 10 mg demonstrated statistically significant improvement in SE and WASO compared to placebo.1
  The most common adverse reaction (reported in 5% or more of patients treated with Dayvigo and at least twice the rate of placebo) in SUNRISE 2 (the first 30 days) and SUNRISE 1 was somnolence (Dayvigo 10 mg, 10%; Dayvigo 5 mg, 7%; placebo, 1%).

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

Experimental antiviral prevents MERS-CoV in rhesus macaques

In continuation of my update on remdesivir 

The experimental antiviral remdesivir successfully prevented disease in rhesus macaques infected with Middle East respiratory syndrome coronavirus (MERS-CoV), according to a new study from National Institutes of Health scientists. Remdesivir prevented disease when administered before infection and improved the condition of macaques when given after the animals already were infected.

The new report from NIH's National Institute of Allergy and Infectious Diseases (NIAID) appears in the Proceedings of the National Academy of Sciences.

MERS-CoV is closely related to the 2019 novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV) that has grown to be a global public health emergency since cases were first detected in Wuhan, China, in December.

Remdesivir has previously protected animals against a variety of viruses in lab experiments. The drug has been shown experimentally to effectively treat monkeys infected with Ebola and Nipah viruses. Remdesivir also has been investigated as a treatment for Ebola virus disease in people.

The current study was conducted at NIAID's Rocky Mountain Laboratories in Hamilton, Montana. The work involved three groups of animals: those treated with remdesivir 24 hours before infection with MERS-CoV; those treated 12 hours after infection (close to the peak time for MERS-CoV replication in these animals); and untreated control animals.

The scientists observed the animals for six days. All control animals showed signs of respiratory disease. Animals treated before infection fared well: no signs of respiratory disease, significantly lower levels of virus replication in the lungs compared to control animals, and no lung damage. Animals treated after infection fared significantly better than the control animals: disease was less severe than in control animals, their lungs had lower levels of virus than the control animals, and the damage to the lungs was less severe.

The scientists indicate that the promising study results support additional clinical trials of remdesivir for MERS-CoV and COVID-19, the disease that SARS-CoV-2 causes. Several clinical trials of remdesivir for COVID-19 are under way in China, and other patients with COVID-19 have received the drug under a compassionate use protocol.

The Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, also provided support for this study. Gilead Sciences, Inc., developed remdesivir, also known as GS-5734, and collaborated in the research.

MERS-CoV emerged in Saudi Arabia in 2012. Through December 2019, the World Health Organization had confirmed 2,499 MERS-CoV cases and 861 deaths (or about 1 in 3). Because about one-third of MERS-CoV cases spread from infected people being treated in healthcare settings, the scientists suggest that remdesivir could effectively prevent disease in other patients, contacts of patients, and healthcare workers. They also note the drug might help patients who are diagnosed with MERS or COVID-19 if given soon after symptoms start.

https://www.pnas.org/content/early/2020/02/12/1922083117
https://en.wikipedia.org/wiki/Remdesivir

FDA Approves Caplyta (lumateperone) for the Treatment of Schizophrenia in Adults

Intra-Cellular Therapies, Inc. (Nasdaq:ITCI), a biopharmaceutical company focused on the development of therapeutics for central nervous system (CNS) disorders, today announced that Caplyta (lumateperone) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of schizophrenia in adults. The Company expects to initiate the commercial launch of Caplyta in late Q1 2020.

The efficacy of Caplyta 42 mg was demonstrated in two placebo-controlled trials, showing a statistically significant separation from placebo on the primary endpoint, the Positive and Negative Syndrome Scale (PANSS) total score. The most common adverse reactions (≥5% and twice the rate of placebo) for the recommended dose of Caplyta vs placebo were somnolence/sedation (24% vs.10%) and dry mouth (6% vs. 2%).

In pooled data from short term studies, mean changes from baseline in weight gain, fasting glucose, triglycerides and total cholesterol were similar between Caplyta and placebo. The incidence of extrapyramidal symptoms was 6.7% for Caplyta and 6.3% for placebo.

“We believe Caplyta provides healthcare providers a new, safe and effective treatment option to help the millions of adult patients with schizophrenia,” said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies. “This approval represents the culmination of years of scientific research. We are especially grateful to the patients, their caregivers, and the healthcare professionals who have contributed to the development of Caplyta.”

Schizophrenia is a serious mental illness impacting approximately 2.4 million adults in the United States. The clinical presentation of schizophrenia is diverse. Acute episodes are characterized by psychotic symptoms, including hallucinations and delusions, often requiring hospitalization. The disease is chronic and lifelong, often accompanied by depression and gradual deterioration of social functioning and cognitive ability. Patients with schizophrenia often discontinue treatment as a result of side effects such as weight gain and movement disorders.

“Schizophrenia is a complex disease that severely impacts patients and their families,” said Jeffrey A. Lieberman, M.D., Lawrence C. Kolb Professor and Chairman of Psychiatry, Columbia University, College of Physicians and Surgeons and Director, New York State Psychiatric Institute. “Effective treatment provided in a timely fashion can be game-changing for people living with schizophrenia. The efficacy and safety profile of Caplyta approved by the FDA, offers healthcare providers an important new option for treating people living with schizophrenia.”

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

FDA Approves Ubrelvy (ubrogepant) for the Acute Treatment of Migraine

In continuation of my update on Ubrelvy (ubrogepant)

Allergan plc (NYSE: AGN),  announced that the U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for Ubrelvy (ubrogepant) for the acute treatment of migraine with or without aura in adults. Ubrelvy™ is the first and only orally-administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the treatment of migraine attacks once they start. Migraine is a neurological disease characterized by intermittent migraine attacks with symptoms that are often incapacitating. Migraine afflicts 31 million Americans and is the third most common disease and second leading cause of disability worldwide.

"The FDA's approval of Ubrelvy™, a new oral option that is effective in the acute treatment of migraine attacks, is a much-welcomed development for me and for many who care for patients. I can offer my migraine patients a new treatment option that may work for them," said Dr. Peter Goadsby, Neurologist and Professor at King's College, London, and University of California, San Francisco, and a paid consultant for Allergan. "Perhaps even better, I am able to offer a new sense of hope for my patients who struggle for relief from this highly disabling problem."

In clinical trials supporting the FDA's approval, Ubrelvy™ provided quick pain relief for the majority of migraine patients. Ubrelvy™ also met co-primary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, hypersensitivity to light, or hypersensitivity to sound), a recent, more stringent standard of efficacy the FDA set in 2018. Ubrelvy™ provided lasting relief up to 24 hours as well. Ubrelvy™ works in a new way by blocking CGRP, a protein that is released during a migraine attack, from binding to its receptors. It works without constricting blood vessels, which some older treatments are known to do. Ubrelvy™ is non-narcotic, not scheduled, and does not have addiction potential. It has been approved with two dose strengths, 50 mg and 100 mg, and is specially designed so healthcare providers can provide a personalized treatment approach for appropriate patients.

"As someone living with migraine for 14 years, my life seems to be on pause when I experience a migraine attack," said Kristin Molacek, Ubrelvy™ clinical trial patient. "During the clinical trial, my experience with Ubrelvy™ was positive. It relieved the migraine symptoms that bothered me the most without serious side effects. We have needed this type of on-demand oral relief for a very long time, and I look forward to having the ability to better manage my migraine attacks."

"We are extremely pleased that Ubrelvy™ is now approved by the FDA. As the first oral gepant, Ubrelvy™ offers a new and different type of acute treatment option for people living with the debilitating pain and other symptoms of migraine," said David Nicholson, EVP and Chief R&D Officer, Allergan. "Its oral administration with two dose strengths allows for treatment flexibility and relief when a migraine attack occurs. As we continue to drive innovation in migraine treatment, we are very proud to offer patients another option, and we are confident that it will make a difference for those in need. At Allergan, we believe that migraine patients deserve access to all new medications for this debilitating disease."

About Ubrelvy (ubrogepant)

Ubrelvy (ubrogepant) is a novel, highly potent, orally-administered calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) for the acute treatment of migraine with or without aura in adults that is an option for a wide range of patients who experience migraine attacks. It works in a new way by blocking CGRP, a protein released during a migraine attack, from binding to its receptors. It works without constricting blood vessels, which some older treatments are known to do. CGRP receptor antagonism is a completely new mechanism of action for the acute treatment of migraine.

The FDA approval for Ubrelvy is based on four clinical studies (ACHIEVE I, ACHIEVE II, UBR-MD-04 and 3110-105-002), which demonstrated efficacy, safety and tolerability of orally-administered Ubrelvy in the acute treatment of migraine. The two pivotal Phase 3 clinical trials (ACHIEVE I and ACHIEVE II) established the safety and efficacy profile of Ubrelvy. Both 50 mg and 100 mg dose strengths demonstrated significantly greater rates of pain freedom and freedom from the most bothersome migraine-associated symptom at two hours, compared with placebo.

Nausea was the most common adverse event reported in 1.7-4.1% of patients at various doses during the pivotal studies, compared to 1.6-2.0% of patients who received placebo. There were no serious adverse events within 48 hours of a dose. Additionally, the safety study (UBR-MD-04) reinforced the long-term safety and tolerability of Ubrelvy for both the 50 mg and 100 mg dose strengths. Our research shows that Ubrelvy was well tolerated with an adverse event profile similar to placebo.

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

Overdose, Relapse After Buprenorphine Discontinuation High

In continuation of my update on buprenorphine

Buprenorphine treatment may be needed for several years after an opioid overdose to reduce the risk of overdose and other adverse events, according to a study published online Dec. 2 in The American Journal of Psychiatry.

Arthur Robin Williams, M.D., from the New York State Psychiatric Institute at the Columbia University Medical Center in New York City, and colleagues used the MarketScan multistate Medicaid claims database (2013 to 2017) to identify adults (18 to 64 years of age) who received buprenorphine continuously for ≥180 days. Outcomes were assessed by buprenorphine duration period (six to nine months, nine to 12 months, 12 to 15 months, and 15 to 18 months).

The researchers found that adverse events were common across all cohorts, and almost half of patients (42.1 to 49.9 percent) were seen in the emergency department at least once. Patients retained for 15 to 18 months (931 patients) had significantly lower odds of emergency department visits (odds ratio, 0.75), inpatient hospitalizations (odds ratio, 0.79), and filling opioid prescriptions (odds ratio, 0.67) in the six months following discontinuation, compared to patients retained on buprenorphine for six to nine months (4,126 patients). Across cohorts, approximately 5 percent of patients experienced one or more medically treated overdoses.

"Patients and families need guidance, social support, and better coordination of care to help facilitate long-term maintenance with buprenorphine for opioid use disorder," Williams said in a statement.

https://www.drugbank.ca/drugs/DB00921

Exeltis USA, Inc. Announces the Approval of Slynd (drospirenone), the First and Only Progestin-Only Pill Providing Pregnancy Prevention with a 24/4 Dosing Regimen and 24-hour Missed Pill Window

Exeltis USA, Inc. a division of the global pharmaceutical group Insud Pharma, announced today that the US Food and Drug Administration (FDA) has approved the new drug application (NDA) for Slynd (pronounced "slind") containing drospirenone 4 mg, an oral contraceptive tablet for pregnancy prevention.

Slynd, a progestin (see above structure) -only pill (POP) is a novel estrogen-free oral contraceptive that is intended as a 24 active with 4 inactive tablet dosing regimen and also allows a 24-hour missed pill window.  This not only can mean favorable safety and efficacy but an improved bleeding profile and contraceptive efficacy for up to 24 hours in the event of a delayed or missed dose.

In clinical trials, Slynd (a synthetic form of progesterone that has a similar pharmacological profile to the natural hormone progesterone) showed no instances of thromboembolic events experienced by some women taking COCs, which by definition contain estrogen.  In addition, the safety of Slynd™ is supported by its approval with no black box warning unlike other combined oral contraceptives.  But for females with conditions that predispose to hyperkalemia (e.g. renal impairment, hepatic impairment and adrenal insufficiency), Slynd™ is contraindicated due to its anti-mineralocorticoid activity.

"This safety profile was demonstrated for all patients, including higher-risk populations like smokers, older women, and subjects with a Body Mass Index (BMI) >30," said Enrico Colli, MD, Chief Scientific Officer.

Salustiano Perez, President of Exeltis USA, Inc. observed "Slynd may be an excellent choice for women who need or want safe and effective oral contraception without the risks of estrogen. Slynd may be an ideal choice for a breastfeeding mother."

Slynd™ is indicated to prevent pregnancy among females of reproductive potential. Contraindications include renal impairment, adrenal insufficiency, presence or history of progestin sensitive cancers, liver tumors, benign or malignant, or hepatic impairment, or undiagnosed abnormal uterine bleeding.

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

New Antibiotic Xenleta Approved for Community-Acquired Bacterial Pneumonia

Xenleta (lefamulin) has been approved to treat adults with community-acquired bacterial pneumonia, the U.S. Food and Drug Administration announced today.

Dosing of Xenleta is either an oral administration of 600 mg every 12 hours or an intravenous administration of 150 mg every 12 hours for five to seven days. Patients can be started on either intravenous or oral therapy or can transition from intravenous to oral therapy to accelerate hospital discharge.

Approval was based on data from two clinical trials of 1,289 patients with community-acquired bacterial pneumonia comparing Xenleta taken orally or intravenously to treatment with moxifloxacin with or without linezolid. Clinical success rates of patients treated with Xenleta were similar to those of patients treated with moxifloxacin with or without linezolid.

The most commonly reported adverse reactions with Xenleta include diarrhea, nausea, injection site reactions, elevated liver enzymes, and vomiting. The FDA notes that Xenleta can cause a prolonged QT interval, so patients with arrythmias, those taking antiarrhythmic agents, and patients receiving other drugs that prolong the QT interval should avoid Xenleta. Patients with known hypersensitivity to lefamulin, other members of the pleuromutilin antibiotic class, or any components of Xenleta are also contraindicated. Health care providers should advise pregnant women and those who could become pregnant of the risk for fetal harm with Xenleta as shown in animal studies. Women who could become pregnant should use effective contraception during and two days after taking Xenleta.

Approval of Xenleta was granted to Nabriva Therapeutics. The drug is expected to be available in mid-September with a wholesale acquisition price of $205 per IV patient treatment day and $275 per oral patient treatment day.

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

FDA Accepts Correvio's Resubmitted New Drug Application for Brinavess (vernakalant)

In continuation of my update on vernakalant 

Correvio Pharma Corp. (CORV) (CORV), a specialty pharmaceutical company focused on commercializing hospital drugs, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the resubmitted New Drug Application (NDA) for Brinavess™ (vernakalant hydrochloride, IV), an antiarrhythmic drug for the rapid conversion of recent onset atrial fibrillation (AF) to sinus rhythm in adult patients.  The FDA assigned a target action date of December 24, 2019 under the Prescription Drug User-Fee Act (PDUFA).  In its acceptance letter, the FDA stated that it is currently planning to hold an advisory committee meeting to discuss this application.

"The FDA's acceptance of this resubmitted NDA marks another important milestone for Correvio and for the global Brinavess program," said Mark H.N. Corrigan, MD, CEO of Correvio.  "As a potential new AF treatment, with a well-characterized efficacy and safety profile, we believe that Brinavess, if approved, will be an attractive addition to the AF treatment landscape.  We look forward to working with the FDA during the review process."

The Company also announced certain preliminary financial results for the second quarter ended June 30, 2019.  Revenue for the second quarter is expected to be in the range of $7.2 to 7.6 million (USD), which represents an approximately 20% increase compared to the second quarter of 2018, despite 5% weakness in the Euro.  As of June 30, 2019, Correvio had cash, cash equivalents and unrestricted cash totalling approximately $12.9 million (USD).  The Company will report its full financial results in August.

The Brinavess NDA is supported by data from SPECTRUM, a post-authorization safety study that was conducted in Europe which evaluated 1,778 unique patients across a total of 2,009 treatment episodes following administration of Brinavess.  The SPECTRUM data demonstrated that treatment with Brinavess successfully converted 70.2% of those treated AF patients into normal sinus rhythm.  In addition, treatment with Brinavess showed a median time to conversion of 11 minutes from the start of the first infusion among patients who successfully converted.  The cumulative incidence of health outcomes of interest (defined as significant hypotension, ventricular arrhythmia, atrial flutter, or bradycardia) was reported in 0.8% of patients.  Twenty-eight serious adverse events were reported in 26 of the 1,778 patients and no deaths were reported in the study.  In addition to SPECTRUM, the Brinavess NDA is supported by nine Phase 3 and Phase 2 clinical trials and over eight years of post-marketing experience in approximately 50,000 treatment patients worldwide.  Brinavess has received marketing authorizations in 41 countries outside the U.S.

About Atrial Fibrillation

Atrial Fibrillation (also known as AFib or AF) is a supraventricular tachyarrhythmia with uncoordinated atrial activation resulting in ineffective atrial contraction and if left untreated, structural and/or electrophysiological atrial tissue abnormalities. AF is a common cardiac rhythm disturbance that increases in prevalence with advancing age. According to the American Heart Association, estimates of the prevalence of AF in the U.S. ranged from 2.7 million to 6.1 million in 2010, and is expected to rise to between 5.6 million to 12 million in 2030.

There are two strategies to manage AF, namely, rhythm- or rate-control. A rhythm-control strategy may be used in patients who are severely compromised, remain symptomatic despite adequate rate control, when adequate rate control is difficult to achieve, when long term rhythm control therapy is preferred, younger patient age, presence of tachycardia-mediated cardiomyopathy, and first episode of AF. Early intervention with a rhythm-control strategy to prevent progression of AF may be particularly beneficial to the AF patient.

About Brinavess

Brinavess (vernakalant HCl, IV) is an antiarrhythmic drug that acts preferentially in the atria by prolonging atrial refractoriness and slowing impulse conduction in a rate-dependent fashion. Brinavess is approved for marketing in Europe, Canada and several other countries worldwide. In Europe, it is approved for the rapid conversion of recent onset atrial fibrillation to sinus rhythm in adults: 1) for non-surgery patients: atrial fibrillation < 7 days duration; and 2) for post-cardiac surgery patients: atrial fibrillation <3 days duration. Vernakalant IV is not approved for use in the United States.

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

Epizyme Announces FDA Filing Acceptance of New Drug Application and Priority Review for Tazemetostat for the Treatment of Epithelioid Sarcoma

Epizyme, Inc. (Nasdaq: EPZM), a late-stage biopharmaceutical company developing novel epigenetic therapies, today announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the company’s New Drug Application (NDA) for accelerated approval of tazemetostat, its lead investigational agent. Epizyme has proposed an indication of metastatic or locally advanced epithelioid sarcoma not eligible for curative surgery. The FDA granted Priority Review for the NDA and has set a Prescription Drug User Fee Act (PDUFA) target action date of January 23, 2020. Priority Review is granted to investigational therapies that, if approved, may offer significant improvements in the treatment, prevention or diagnosis of a serious condition.

“We are thrilled with FDA’s acceptance of this first tazemetostat NDA submission for priority review, and to be an important step closer to achieving our mission of rewriting treatment for patients with cancer and other serious diseases,” said Robert Bazemore, president and chief executive officer of Epizyme. “This is a significant achievement in the development of this potentially first-in-class EZH2 inhibitor, and we look forward to working with FDA during the review. If approved, we believe tazemetostat could become an important new option in the treating physicians’ arsenal. We would like to extend our sincerest gratitude to those patients, families and medical teams who have participated in our clinical studies and helped bring tazemetostat to this stage.”

Epizyme’s NDA submission is based primarily on data from the 62 patient epithelioid sarcoma cohort of its ongoing Phase 2 study of tazemetostat. These data, recently reported at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, showed that tazemetostat treatment resulted in clinically meaningful and durable responses, and was generally well-tolerated.

To support full approval of tazemetostat for epithelioid sarcoma, Epizyme will initiate a global confirmatory trial. The company plans to conduct a 1:1 randomized, controlled clinical trial in the front-line treatment setting comparing tazemetostat in combination with doxorubicin versus placebo plus doxorubicin in approximately 150 patients. The primary efficacy endpoint will be progression-free survival, and secondary efficacy endpoints will include overall survival, disease control rate, overall response rate and duration of response. The confirmatory study will include a safety run-in that is expected to begin in the second half of 2019.

About the Tazemetostat Clinical Trial Program 

Tazemetostat, an oral, potent, first-in-class EZH2 inhibitor, is currently being studied as a monotherapy in ongoing clinical programs in patients with certain molecularly defined solid tumors, including epithelioid sarcoma and other INI1-negative tumors, and in patients with follicular lymphoma, both with and without EZH2 activating mutations. Multiple clinical studies are underway through collaborations assessing tazemetostat as a combination treatment for patients with diffuse large B-cell lymphoma. Epizyme also plans to conduct multiple additional clinical trials designed to evaluate the potential benefit of tazemetostat in earlier lines of therapy for follicular lymphoma, as well as new combinations and cancer indications.

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

Sunovion Announces Acceptance by the U.S. FDA of the New Drug Application for Dasotraline for the Treatment of Adults with Moderate-to-Severe Binge Eating Disorder

In continuation of my update on dasotraline,

Sunovion Pharmaceuticals Inc.(Sunovion) today announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for dasotraline, a novel dopamine and norepinephrine reuptake inhibitor (DNRI), for the treatment of patients with moderate-to-severe binge eating disorder (BED). Dasotraline’s pharmacokinetic profile, characterized by an extended half-life, supports its potential for sustained control of moderate-to-severe BED symptoms.

The action date by the FDA under the Prescription Drug User Fee Act (PDUFA) is May 14, 2020.

Dasotraline is an investigational, once-daily medication that demonstrated significant efficacy for the treatment of moderate-to-severe BED in two 12-week, randomized, placebo-controlled studies, SEP360-221 and SEP360-321. Dasotraline was found to be generally well tolerated in clinical studies, including a long-term safety study, SEP360-322, that assessed patients with moderate-to-severe BED for up to one year.

“Binge eating disorder is a serious mental health condition for which limited treatment options exist. The disorder is often seen in association with other behavioral conditions such as depression, substance abuse and post-traumatic stress disorder, and it is often under-diagnosed and under-treated,” said Antony Loebel, M.D., President and Chief Executive Officer at Sunovion. “We are confident in the value dasotraline has shown in clinical trials to people living with BED and look forward to working with the FDA to advance this novel treatment option.”

According to the American Psychiatric Association in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (DSM-5),2,3 BED is characterized by recurrent and persistent episodes of binge eating, defined as consuming large quantities of food in a short period of time, perception of loss of control during the episode, and intense feelings of shame, guilt and embarrassment afterwards. Many individuals also suffer from depressive and anxiety symptoms, as well as a number of medical complications, leading to impaired functioning and quality of life.

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

Blueprint Medicines Announces FDA Acceptance of New Drug Application for Avapritinib for the Treatment of PDGFRA Exon 18 Mutant GIST and Fourth-Line GIST

Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy, today announced that the U.S. Food and Drug Administration (FDA) has accepted the company's New Drug Application (NDA) for avapritinib for the treatment of adult patients with PDGFRA Exon 18 mutant gastrointestinal stromal tumors (GIST), regardless of prior therapy, and fourth-line GIST. The FDA granted Priority Review and set an action date of February 14, 2020 under the Prescription Drug User Fee Act (PDUFA). At this time, the FDA is not planning to hold an advisory committee meeting to discuss this application. Avapritinib, an investigational therapy, is a potent and highly selective KIT and PDGFRA inhibitor for patients with advanced GIST.

"Patients with PDGFRA Exon 18 mutant GIST and fourth-line GIST are in need of new treatment options that address the underlying drivers of the disease," said Andy Boral, M.D., Ph.D., Chief Medical Officer at Blueprint Medicines. "The FDA's acceptance of our application for Priority Review brings us closer to our goal of delivering avapritinib to patients with GIST, and we look forward to working closely with the FDAduring the review process."

The FDA's acceptance of the NDA indicates the application is sufficiently complete to permit a substantive review. A Priority Review designation accelerates the FDA's review time from 12 months to a goal of eight months from the NDA submission date, and is granted to drugs that may offer a significant improvement in the safety or effectiveness of the treatment, prevention or diagnosis of a serious condition. Previously, the FDA granted avapritinib Breakthrough Therapy Designation for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation.

In July 2019, the European Medicines Agency validated Blueprint Medicines' Marketing Authorization Application for avapritinib in adult patients with PDGFRα D842V mutant GIST, regardless of prior therapy, and fourth-line GIST.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50 to 80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

Most GIST cases are caused by a spectrum of clinically relevant mutations that force the KIT or PDGFRA protein kinases into an increasingly active state. Because currently available therapies primarily bind to the inactive protein conformations, certain primary and secondary mutations typically lead to treatment resistance and disease progression.

In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. Mutational testing is critical to tailor therapy to the underlying disease driver and is recommended in expert guidelines. Currently, there are no approved therapies for patients with KIT-driven GIST whose disease progresses beyond imatinib, sunitinib and regorafenib. In patients with metastatic PDGFRα D842V-driven GIST, progression occurs in a median of approximately three to four months with available therapy.

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