FDA Approves Sunosi

 Jazz Pharmaceuticals plc   announced that the U.S. Food and Drug Administration (FDA) approved Sunosi (solriamfetol) to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea (OSA). Once-daily Sunosi is approved with doses of 75 mg and 150 mg for patients with narcolepsy and doses of 37.5 mg, 75 mg, and 150 mg for patients with OSA. Sunosi is the first dual-acting dopamine and norepinephrine reuptake inhibitor (DNRI) approved to treat excessive daytime sleepiness in adults living with narcolepsy or OSA.

Sunosi is expected to be commercially available in the U.S. following the final scheduling decision by the U.S. Drug Enforcement Administration (DEA), which is typically within 90 days of FDA approval.

"Excessive daytime sleepiness can negatively impact the daily lives of people living with narcolepsy or obstructive sleep apnea at work, at home or in daily activities. With this approval, a new, daytime medicine that can provide sustained wakefulness throughout the day will be available for patients," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "The FDA approval of Sunosi also represents an important milestone for Jazz as we continue to offer new treatment options that address unmet needs for people living with chronic, and often debilitating, sleep disorders."

At Week 12, 150 mg of Sunosi for narcolepsy patients and all doses for OSA patients demonstrated improvements in wakefulness compared to placebo as assessed in test sessions 1 (approximately one hour post-dose) through 5 (approximately nine hours post-dose) of the maintenance of wakefulness test (MWT).

The FDA's approval of Sunosi is based on data from the Treatment of Obstructive sleep apnea and Narcolepsy Excessive Sleepiness (TONES) Phase 3 clinical program, which included four randomized placebo-controlled studies that demonstrated the superiority of Sunosi relative to placebo. The most common adverse reactions (incidence ≥5% and higher than placebo) reported in both the narcolepsy and OSA study populations were headache, nausea, decreased appetite, and anxiety. Sunosi was evaluated in more than 900 adults with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea and was shown to maintain its effect relative to placebo after six months of use.

"We're excited about this new therapeutic option for patients, and we are pleased with the information included in the Sunosi label as we believe it will give physicians the information needed to appropriately manage the vast majority of obstructive sleep apnea and narcolepsy patients with excessive daytime sleepiness," said Daniel Swisher, president and chief operating officer of Jazz Pharmaceuticals.

In 12 week clinical studies, approximately 68-74% of people taking Sunosi at the 75 mg dose and 78-90% of people taking Sunosi at the 150 mg dose reported improvement in their overall clinical condition, as assessed by the Patient Global Impression of Change (PGIc) scale.

Although the exact mechanism of action is unknown, the effects of Sunosi are thought to be mediated through its activity as a DNRI.

"Sunosi is an effective treatment option with a novel mechanism of action as a dual-acting dopamine and norepinephrine reuptake inhibitor," said Richard K. Bogan, MD, FCCP, FAASM, Associate Clinical Professor at the University of South Carolina School of Medicine and Chief Medical Officer at SleepMed in Columbia, SC. "Excessive daytime sleepiness is the most common symptom for people with narcolepsy and a major complaint of people with obstructive sleep apnea. In some people with obstructive sleep apnea, excessive daytime sleepiness may persist despite using CPAP."

Sunosi is not indicated to treat the underlying airway obstruction in OSA. Ensure that the underlying airway obstruction is treated (e.g., with continuous positive airway pressure (CPAP)) for at least one month prior to initiating Sunosi for excessive daytime sleepiness in OSA. Modalities to treat the underlying airway obstruction should be continued during treatment with Sunosi. Sunosi is not a substitute for these modalities.

About Sunosi (solriamfetol)

Sunosi is a dual-acting dopamine and norepinephrine reuptake inhibitor (DNRI) indicated to improve wakefulness in adults living with excessive daytime sleepiness due to narcolepsy or obstructive sleep apnea (OSA). In 2014, Jazz Pharmaceuticals acquired a license to develop and commercialize Sunosi from Aerial Biopharma. Jazz Pharmaceuticals has worldwide development, manufacturing, and commercialization rights to Sunosi, excluding certain jurisdictions in Asia. SK Biopharmaceuticals, the discoverer of the compound, maintains rights in 12 Asian markets, including Korea, China and Japan. Sunosi has orphan drug designation for narcolepsy in the United States. 

Important Safety Information

Sunosi can be a target for people who abuse prescription medicines or street drugs. Keep Sunosi in a safe place to protect it from theft. Never give your Sunosi to anyone else, because it may cause death or harm them. Selling or giving away Sunosi may harm others and is against the law. Tell your doctor if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.

Do not take Sunosi if you are taking or have stopped taking within the past 14 days a medicine used to treat depression called a monoamine oxidase inhibitor (MAOI).

Before taking Sunosi, tell your doctor about all of your medical conditions, including if you:

• have heart problems, high blood pressure, kidney problems, diabetes, or high cholesterol
• have had a heart attack or a stroke
• have kidney problems or diabetes
• have a history of mental health problems, (including psychosis and bipolar disorders), or of drug or alcohol abuse or addiction
• are pregnant or planning to become pregnant. It is not known if Sunosi will harm your unborn baby.
• Pregnancy Registry: There is a pregnancy registry for women who take Sunosi during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your doctor about how you can take part in this registry.
• are breastfeeding or plan to breastfeed. It is not known if Sunosi passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take Sunosi.

Especially tell your healthcare provider if you take a medicine used to treat depression called a monoamine oxidase inhibitor (MAOI).

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

FDA Approves Sunosi (solriamfetol) for Excessive Daytime Sleepiness Associated with Narcolepsy or Obstructive Sleep Apnea..

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Eating blueberries every day could help decrease blood pressure

In continuation of my update on blueberries

A new study published in the Journal of Gerontology Series A has found that eating 200g of blueberries every day for a month can lead to an improvement in blood vessel function and a decrease in systolic blood pressure in healthy people.

Researchers from King's College London studied 40 healthy volunteers for one month. They were randomly given either a drink containing 200g of blueberries, or a matched control drink daily.

The team monitored chemicals in volunteers' blood and urine as well as their blood pressure and flow-mediated dilation (FMD) of the brachial artery: a measure of how the artery widens when blood flow increases, which is considered a sensitive biomarker of cardiovascular disease risk.

In a further study, researchers compared the effects of a blueberry drink with those of purified anthocyanins, a type of phytochemical responsible for the blue, red, pink and purple colour of some fruits and vegetables such as berries and red grapes. They also compared this with control drinks containing either similar levels of fiber, mineral or vitamins found in blueberries.

They found that:

• Effects on blood vessel function were seen two hours after consumption of the blueberry drinks and were sustained for one month even after an overnight fast.
• Over the course of the month, blood pressure was reduced by 5mmHg. This is similar to what is commonly seen in studies using blood pressure lowering medication.
• The drinks containing purified anthocyanins led to improvements in endothelial function. Endothelial cells act as a barrier between the blood or lymph and the surrounding body tissue, as well as playing key roles in blood clotting and regulating blood pressure.
• Neither the control drink, the control with fiber or the control with minerals and vitamins had a significant effect on FMD at two and six hours after consumption.

Lead researcher Dr Ana Rodriguez-Mateos from the Department of Nutritional Sciences at King's College London said: "Although it is best to eat the whole blueberry to get the full benefit, our study finds that the majority of the effects can be explained by anthocyanins.

"If the changes we saw in blood vessel function after eating blueberries every day could be sustained for a person's whole life, it could reduce their risk of developing cardiovascular disease by up to 20%."

https://www.kcl.ac.uk/news/news-article?id=af4e7b3e-2c7d-4d8f-ae9e-fe6d1014d0eb

Eating blueberries every day could help decrease blood pressure

Some drug combinations may be more effective than others for schizophrenic patients

  Patients with schizophrenia are often treated with more than one type of psychiatric medication, but a new study suggests that some combinations may be more effective than others.

The findings were published in JAMA Psychiatry.

Antipsychotic drugs are usually the first line of treatment for individuals with schizophrenia. But because these drugs often fail to control symptoms adequately on their own, doctors often prescribe additional psychiatric medications, such as another antipsychotic, an antidepressant, a benzodiazepine, or a mood stabilizer.

"Antipsychotic medications are used to treat psychotic symptoms such as delusions and hallucinations but there is little guidance on what to do for other types of symptoms like depression, anxiety or excitement. Additional medications are often prescribed, but we know little about how different psychiatric drug combinations affect people with schizophrenia," says T. Scott Stroup, MD, MPH, professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons and lead author of the paper. "Until now we have known virtually nothing about how these strategies compare to each other."

To find out, the researchers conducted a comparative effectiveness study using Medicaid records of 81,921 adults with schizophrenia who had been taking only an antipsychotic drug for at least 3 months before starting either an antidepressant, benzodiazepine, mood stabilizer, or another antipsychotic drug.

The researchers found that individuals with schizophrenia who added an antidepressant were less likely to land in the emergency room or hospital for a mental health issue than those who started another antipsychotic or a benzodiazepine. Antidepressants reduced the risk of hospitalization by 16% compared to antipsychotics and by 22% compared to benzodiazepines. For emergency room visits, antidepressants reduced the risk by 8% compared to antipsychotics and by 18% compared to benzodiazepines.

"Our study adds more evidence that benzodiazepine use should be limited and that combining antidepressants with antipsychotic drugs for individuals with schizophrenia may have benefits," says Stroup. "We still need to know more about when to use antidepressants, which may be useful for conditions other than depression."

Combining medications is often referred to as polypharmacy. "The results of our study should promote rational polypharmacy," added Stroup. He thinks that clinicians will find the results believable and hopes that they will lead to practice changes and improved patient outcomes.

The study is titled, "Comparative Effectiveness of Adjunctive Psychotropic Medications in Patients with Schizophrenia."

https://www.cuimc.columbia.edu/

Some drug combinations may be more effective than others for schizophrenic patients

Drug increases melanin production in some people with albinism

  

A small pilot clinical study at the National Eye Institute (NEI) suggests that the drug nitisinone increases melanin production in some people with oculocutaneous albinism type 1B (OCA-1B), a rare genetic disease that causes pale skin and hair and poor vision. Increased melanin could help protect people with the condition against the sun's UV rays and promote the development of normal vision. Study results were published in JCI Insight. NEI is part of the National Institutes of Health (NIH).

"Because the greatest vision problems for people with albinism occur during the early development of the eye, our eventual goal is to work with infants," said Brian Brooks, M.D., Ph.D., clinical director at NEI and lead author of the study. "The purpose of this pilot study was to explore whether nitisinone is safe and whether we could pick up a signal that the drug works."

Oculocutaneous albinism (OCA) is a rare inherited disease caused by mutations in genes needed to make melanin, a dark-colored pigment found in hair, skin, and eyes. In the United States, the most common form of OCA is OCA-1, which is caused by mutations in the gene that codes for the enzyme tyrosinase. Tyrosinase function - the breakdown of the amino acid tyrosine into its component parts - is critical for the production of melanin. People with OCA-1B, like those who participated in this study, have some tyrosinase, but it functions poorly. People with OCA-1A have no tyrosinase at all. Approximately one in 17,000 people worldwide have a form of OCA.

The study followed three women and two men over 18 months, including 12 months on a daily oral 2 mg dose of nitisinone, and six additional months without the drug. While on nitisinone, most study participants showed a slight darkening of skin and hair. One participant's skin darkened slightly after sun exposure. However, the researchers were unable to detect clinically significant changes in eye melanin or in visual acuity. With improvements in imaging of the iris, and with younger patients, Brooks and colleagues hope subtle changes in the eye will be more apparent.

Nitisinone increases the concentration of the amino acid tyrosine in the blood. In people with OCA-1B, Brooks believes that the higher levels of tyrosine help stabilize mutated tyrosinase and make the enzyme more effective. Brooks' previous studies have shown that nitisinone has no effect in OCA-1A, where there's no tyrosinase to stabilize, and OCA-3, where a different part of the melanin pathway is affected, so his team doesn't intend to pursue this drug for patients with those forms of albinism. Nitisinone is approved by the U.S. Food and Drug Administration to treat a rare metabolic disease called tyrosinemia, which can cause liver and neurological problems.

"We're evaluating OCA-2 and OCA-4 in mice, and we're hopeful that this drug might have some effect," said Brooks. In the meantime, he hopes to start a new, larger trial of nitisinone for teenagers with OCA-1B.

"Melanin is crucial for normal visual development during infancy, but the eye continues to develop and change throughout childhood and into the teenage years," Brooks said. For this reason, Brooks thinks nitisinone might improve iris pigmentation and visual acuity in teens and could have a bigger effect in younger children with OCA-1B.

On February 28, NIH will recognize Rare Disease Day, established in 2008 to raise awareness about rare diseases and the unique challenges faced by patients and their families. In the United States, a disease is considered rare if it affects less than 200,000, or approximately one in 1700, people. About 80 percent of rare diseases are caused by inherited gene defects, and many of these, like OCA, lack effective treatments. NEI is committed to supporting basic and clinical research into rare diseases that affect vision

Ref : https://nei.nih.gov/content/nitisinone-increases-melanin-people-albinism

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

Drug increases melanin production in some people with albinism

Allergan Announces FDA Approval of Avycaz (ceftazidime and avibactam) for Pediatric Patients

Allergan plc (NYSE: AGN) announced that the U.S. Food and Drug Administration (FDA) has approved the company's supplemental New Drug Application (sNDA) for Avycaz (ceftazidime and avibactam), expanding the label to include pediatric patients 3 months and older for the treatment of complicated intra-abdominal infections (cIAI) in combination with metronidazole and complicated urinary tract infections (cUTI). This is the first FDA approval of a pediatric indication for cUTI and cIAI in more than a decade.

      

"Difficult-to-treat gram-negative pathogens pose a significant health risk, particularly to the vulnerable and sensitive pediatric patient population with few options for treatment," said David Nicholson, Chief Research & Development Officer at Allergan.  "As resistance rises among the gram-negative pathogens that cause these serious infections, the expanded label for Avycaz provides a safe and effective treatment option now for pediatric patients with cIAI and cUTI. These expanded indications in pediatric patients with infections, including infants and those at a particularly young age, address an unmet need among this vulnerable population and  underscore Allergan's efforts in anti-infective research."

The label expansion was approved based on results from two active-controlled clinical studies evaluating Avycaz in children or infants with cIAI or cUTI, as well as a single-dose pharmacokinetic study. In the cIAI study, the safety and efficacy of Avycaz (in combination with metronidazole) was compared with meropenem. In the cUTI study, Avycaz was compared with cefepime.

Across the trials, 128 pediatric patients 3 months to less than 18 years of age were treated with Avycaz. Overall, the findings from the pediatric studies were similar to the previous determination of safety for Avycaz for the treatment of adult patients with cIAI or cUTI, and no new safety concerns were identified in pediatric patients.

The primary objectives of the studies were to evaluate the safety and tolerability of Avycaz, and they were not powered for a statistical analysis of efficacy. The descriptive efficacy analyses in the pediatric studies were consistent with data from studies in adults with cIAI and cUTI. In the pediatric cIAI study, the clinical cure rate at the test-of-cure (TOC) visit in the intent-to-treat (ITT) population was 91.8% (56/61) in the Avycaz plus metronidazole group and 95.5% (21/22) in the meropenem group. Clinical cure rates for the predominant pathogens, Escherichia coli and Pseudomonas aeruginosa, were 90.5% and 85.7%, respectively for patients treated with Avycaz plus metronidazole, and 92.3% and 88.9%, respectively, for patients treated with meropenem. In the pediatric cUTI study, the combined favorable clinical and microbiological response rate at TOC in the microbiological-ITT population was 72.2% (39/54) in the Avycaz group and 60.9% (14/23) in the cefepime group. The microbiologic response rate for E.coli, the most common uropathogen identified in the study, was 79.6% for patients treated with Avycaz and 59.1% for patients treated with cefepime.

Avycaz was first approved by the FDA in February 2015 for the treatment of cUTI including pyelonephritis, and cIAI in combination with metronidazole, caused by designated susceptible bacteria including certain Enterobacteriaceae and P. aeruginosa, for patients 18 years of age and older. Avycaz was subsequently approved for the treatment of adults with hospital-acquired pneumonia / ventilator-associated pneumonia (HABP/VABP) caused by designated susceptible bacteria in February 2018.

About Avycaz (ceftazidime and avibactam)

Avycaz is a fixed-dose combination antibacterial indicated for the treatment of cIAI (in combination with metronidazole), and cUTI caused by designated susceptible Gram-negative microorganisms in patients 3 months or older. Avycaz is also indicated for the treatment  of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults. Avycaz consists of a combination of avibactam and ceftazidime.

Avibactam is a first-in-class non-beta-lactam beta-lactamase inhibitor which protects ceftazidime against degradation by certain beta-lactamases. Avibactam does not decrease the activity of ceftazidime against ceftazidime-susceptible organisms. Ceftazadime is a third-generation cephalosporin with a well-established efficacy and safety profile.

Avycaz has demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC and certain oxacillinases (OXA). Avycaz also demonstrated in vitro activity against P. aeruginosa in the presence of some AmpC beta-lactamases, and certain strains lacking outer membrane porin (OprD). Avycaz is not active against bacteria that produce metallo-beta lactamases and may not have activity against Gram-negative bacteria that overexpress efflux pumps or have porin mutations.

Ceftazidime and avibactam is being jointly developed with Pfizer. Allergan holds the rights to commercialize ceftazidime and avibactam in North America under the brand name Avycaz, while Pfizer holds the rights to commercialize the combination in the rest of the world under the brand 

Ref : https://www.drugbank.ca/drugs/DB00438

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

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

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

Harmony Biosciences Announces File Acceptance Of Its New Drug Application For Pitolisant

   Harmony Biosciences, LLC (Harmony), announced that the U.S. Food and Drug Administration (FDA) has accepted for filing the New Drug Application (NDA) for its investigational product, pitolisant, and has granted Priority Review for this NDA. Pitolisant is a first-in-class molecule with a novel mechanism of action; it is a potent and highly selective histamine 3 (H₃) receptor antagonist/inverse agonist for the potential treatment of excessive daytime sleepiness (EDS) and/or cataplexy in adult patients with narcolepsy. A Priority Review designation by the FDA indicates that, if approved, pitolisant would provide a significant improvement in the safety or effectiveness of the treatment of EDS and/or cataplexy in adult patients with narcolepsy when compared to existing treatments. Harmony’s goal is to obtain FDA approval to market pitolisant in the U.S. in 2019.

“The impact of narcolepsy can be significant and severely disruptive to everyday life for up to 200,000 Americans living with this disorder,” said John C. Jacobs, President and CEO at Harmony. “This is an important step for patients and for our company, whose mission is to develop novel treatment options for people living with rare and orphan diseases.”

“Pitolisant offers a novel approach to the treatment of both EDS and cataplexy in patients with narcolepsy, for which there have been no new treatment options in over 15 years,” said Jeffrey M. Dayno, M.D., Chief Medical Officer at Harmony. “We look forward to working with the FDA during its review of the pitolisant NDA, with our hope of being able to offer this new treatment option to help address an important unmet medical need for people living with narcolepsy.”

The NDA submission is based on results from the clinical development program in narcolepsy, which included over 300 patients, some of whom were treated for up to five years. It also included safety data in over 1500 patients across multiple patient populations.

About Pitolisant

Pitolisant is an investigational medication in the U.S. that is not approved by the FDA. It was granted orphan designation for the treatment of narcolepsy, Fast Track designation for the treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy, and Breakthrough Therapy designation for the treatment of cataplexy in patients with narcolepsy. Pitolisant, a first-in-class medication, is a potent and highly selective histamine 3 (H₃) receptor antagonist/inverse agonist; it enhances the activity of histaminergic neurons in the brain that function to improve a patient’s wakefulness and inhibit attacks of cataplexy. It was designed and developed by Bioprojet, who has marketed the product in Europe since its approval by the European Medicines Agency in 2016. Harmony’s goal is to obtain FDA approval to market this new medication in the U.S. in 2019. If approved, pitolisant would represent the first new therapy in the U.S. in over 15 years for the treatment of both EDS and cataplexy in adult patients with narcolepsy.

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

   

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

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

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

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

About the Diroximel Fumarate Clinical Development Program

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

About Diroximel Fumarate

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

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

Bayer Completes Rolling Submission of NDA for Investigational Drug Darolutamide for the Treatment of Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)

   

Bayer  announced the completion of the rolling submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the investigational drug darolutamide. The submission, which was initiated in December 2018, is based on data from the Phase III ARAMIS trial in men with non-metastatic castration-resistant prostate cancer (nmCRPC).1 These data were recently presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in San Francisco and published simultaneously in The New England Journal of Medicine.

"We are grateful to the patients, their families and the clinical investigators who have made this important study possible," said Scott Z. Fields, M.D., senior vice president and head of Oncology Development at Bayer's Pharmaceutical Division. "The NDA submission is a key milestone bringing us closer to providing darolutamide as a potential treatment option for men with nmCRPC."

Bayer has been granted Fast Track designation by the FDA for darolutamide in men with nmCRPC. Bayer is also in discussions with other health authorities regarding a submission of darolutamide. The compound is being developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

About the ARAMIS Trial

The ARAMIS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral darolutamide in patients with nmCRPC who are currently being treated with androgen deprivation therapy (ADT) as standard of care and are at high risk for developing metastatic disease. 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide twice a day or placebo along with ADT.

The primary endpoint of this trial is metastasis-free survival (MFS) defined as time between randomization and evidence of metastasis or death. The secondary endpoints of this trial are overall survival (OS), time to pain progression, time to initiation of first cytotoxic chemotherapy, time to first symptomatic skeletal event (SSE), and characterization of the safety and tolerability of darolutamide.

About Darolutamide

Darolutamide is an investigational, non-steroidal androgen receptor antagonist with a chemical structure that binds to the receptor and exhibits antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. A Phase 3 study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about these trials can be found at www.clinicaltrials.gov.

Darolutamide is not approved by the U.S. FDA, the European Medicines Agency or any other health authority.

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

FDA Approves Lonsurf (trifluridine/tipiracil) for Adult Patients with Previously Treated Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

In continuation of my update on Lonsurf

Taiho Oncology, Inc.  announced that the United States Food and Drug Administration (FDA) has approved Lonsurf as a treatment for adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

“The approval of Lonsurf represents a significant milestone for patients living with advanced gastric or GEJ adenocarcinoma who have limited effective treatment options after standard treatment options have failed,” said Timothy Whitten, President and Chief Executive Officer, Taiho Oncology, Inc. “We thank all the patients and physicians who helped make this possible through their participation in Lonsurf clinical trials.”

The approval for Lonsurf follows an FDA Priority Review designation and is based on data from a global, randomized, Phase III TAGS trial evaluating Lonsurf plus best supportive care (BSC) versus placebo plus BSC in patients with previously treated advanced gastric cancer or GEJ adenocarcinoma following progression or intolerance to previous lines of standard therapy. The trial met its primary and secondary endpoints demonstrating prolonged overall survival (OS) with Lonsurf versus placebo, and a safety profile consistent with prior experience with this drug. Full results from the TAGS trial were presented at the European Society of Medical Oncology (ESMO) 2018 Congress with a simultaneous publication in The Lancet Oncology.1

“Effective treatments for patients with heavily pretreated advanced gastric and GEJ cancer are limited,” said Martin Birkhofer, MD, Senior Vice President and Chief Medical Officer, Taiho Oncology, Inc. “By improving survival, Lonsurf may provide a significant impact on the lives of these patients.”

This approval expands the current indication for Lonsurf in the United States, where it is currently approved for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with standard chemotherapy, based on results obtained in the RECOURSE trial.

Ref : https://en.wikipedia.org/wiki/Trifluridine/tipiracil

FDA Approves Gloperba (colchicine) for Prophylaxis of Adult Gout Flares

ROMEG Therapeutics, an innovative drug development company focused on alternative formulations to better meet clinical and patient needs,  announced that the U.S. Food and Drug Administration (FDA) approved Gloperba (colchicine) Oral Solution, 0.6 mg/5 mL for prophylaxis of gout flares in adults. Gloperba is the first liquid formulation of colchicine approved by the FDA for the prophylaxis of gout flares.

“Existing therapies do not adequately address the physician’s need to adjust dosages of colchicine to manage the toxicity profile for patients with renal and liver impairments, side effects, common drug-to-drug interactions, and age-related health disorders. The approval of Gloperba addresses a significant unmet and underserved medical need.”

“Gloperba represents an important advancement for patients who are experiencing the recurring, painful effects of gout,” said Naomi Vishnupad, Ph.D., Chief Scientific Officer of ROMEG Therapeutics. “Existing therapies do not adequately address the physician’s need to adjust dosages of colchicine to manage the toxicity profile for patients with renal and liver impairments, side effects, common drug-to-drug interactions, and age-related health disorders. The approval of Gloperba addresses a significant unmet and underserved medical need.”

Gout is a form of arthritis affecting an estimated 8.7 million people in the United States. The current U.S. market for colchicine products is approximately $800 million. The disease is caused by elevated levels of uric acid in the bloodstream, and symptoms from the buildup of uric acid crystals in the joints include sudden, severe attacks of pain, swelling and redness, frequently at the base of the big toe. Gout can become chronic if left untreated.

Physicians have used colchicine to treat gout for decades, but they are often required to adjust the dose or interrupt treatment to address drug interactions or health conditions such as when patients are undergoing kidney dialysis. Compared with currently available capsule and tablet formulations of colchicine, the Gloperba oral solution allows physicians to easily make dosage adjustments for their patients. Gloperba is also beneficial for patients who cannot swallow solid doses or pills. About 15 percent of elderly patients have difficulty swallowing and therefore require liquid formulations.

Gloperba will be available at chain, independent and speciality pharmacies, long-term care facilities, and hospitals across the U.S. in summer 2019.

Ref: https://www.rxlist.com/gloperba-drug.htm#indications

AbbVie Announces New Drug Application Accepted for Priority Review by FDA for Upadacitinib for Treatment of Moderate to Severe Rheumatoid Arthritis

  

In continuation of my update on upadacitinib 

AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, has announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review its New Drug Application (NDA) for upadacitinib for the treatment of adult patients with moderate to severe rheumatoid arthritis. Upadacitinib is an investigational once-daily oral JAK1-selective inhibitor being studied for multiple immune-mediated diseases.1-13 AbbVie anticipates a regulatory decision in Q3 2019.

The NDA is supported by data from the global upadacitinib SELECT Phase 3 rheumatoid arthritis program evaluating more than 4,000 patients with moderate to severe rheumatoid arthritis across five of six Phase 3 studies.3-7 In all SELECT Phase 3 studies, upadacitinib met all primary and ranked secondary endpoints. The most frequent serious adverse events were infections.3-7 Top-line results from these clinical studies were previously announced.

Upadacitinib is also under review by the European Medicines Agency for the treatment of adult patients with moderate to severe rheumatoid arthritis.

About the SELECT Study Program 

The robust SELECT Phase 3 rheumatoid arthritis program evaluates more than 4,900 patients with moderate to severe rheumatoid arthritis in six studies, five of which support regulatory submission for upadacitinib. The studies include assessments of efficacy, safety and tolerability across a broad range of rheumatoid arthritis patients. Key measures of efficacy evaluated include ACR responses, Disease Activity Score (DAS28-CRP) and inhibition of radiographic progression. More information on these trials can be found at www.clinicaltrials.gov (NCT02706847, NCT03086343, NCT02629159, NCT02706873, NCT02706951, NCT02675426).

About Upadacitinib

Discovered and developed by AbbVie, upadacitinib is an investigational oral, small molecule JAK1-selective inhibitor being studied for moderate to severe rheumatoid arthritis and other immune-mediated diseases.1-2 The FDA granted priority review for AbbVie's NDA for moderate to severe rheumatoid arthritis in Q1 2019. Phase 3 trials of upadacitinib in atopic dermatitis, psoriatic arthritis, Crohn's disease, and ulcerative colitis are ongoing and it is also being investigated to treat ankylosing spondylitis.9-13Upadacitinib is not approved and its safety and efficacy have not been evaluated by regulatory authorities.

Gilead Announces Topline Data From Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)

Gilead Sciences, Inc. (Nasdaq: GILD) announced that STELLAR-4, a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib, an investigational, once-daily, oral inhibitor of apoptosis signal-regulating kinase 1 (ASK1), in patients with compensated cirrhosis (F4) due to nonalcoholic steatohepatitis (NASH), did not meet the pre-specified week 48 primary endpoint of a ≥ 1-stage histologic improvement in fibrosis without worsening of NASH.

 

In the study of 877 enrolled patients who received study drug, 14.4 percent of patients treated with selonsertib 18 mg (p=0.56 vs. placebo) and 12.5 percent of patients treated with selonsertib 6 mg (p=1.00) achieved a ≥ 1-stage improvement in fibrosis according to the NASH Clinical Research Network (CRN) classification without worsening of NASH after 48 weeks of treatment, compared with 12.8 percent of patients who received placebo. Selonsertib was generally well-tolerated and safety results were consistent with prior studies.

“While we are disappointed that the STELLAR-4 study did not achieve its primary endpoint, we remain committed to advancing therapies for patients with advanced fibrosis due to NASH, where there is a significant unmet need for effective and well-tolerated treatments. Gilead has a long-term commitment and proven track record of addressing significant challenges in the field of liver diseases. Data from this large study of patients with compensated cirrhosis due to NASH, including the extensive set of biomarkers collected, will further advance our understanding of the disease and inform our broader NASH development programs,” said John McHutchison, AO, MD, Chief Scientific Officer, Head of Research and Development, Gilead. “We are grateful to the patients and investigators who participated in the STELLAR-4 study, and we now await the upcoming results from the Phase 3 STELLAR-3 trial of selonsertib in patients with bridging fibrosis (F3) due to NASH and the Phase 2 ATLAS combination trial of selonsertib, cilofexor (GS-9674) and firsocostat (GS-0976) in patients with advanced fibrosis due to NASH later this year.”

Further in-depth analysis of the findings is ongoing and the data will be submitted to an upcoming scientific conference. Gilead will work with the Data Monitoring Committee and investigators to conclude the STELLAR-4 study in a manner consistent with the best interests of each patient.

Selonsertib, cilofexor and firsocostat, alone or in combination, are investigational compounds and are not approved by the U.S. Food & Drug Administration (FDA) or any other regulatory authority. Safety and efficacy have not been established for these agents.

About Selonsertib and the STELLAR-4 Study

Selonsertib is an investigational small molecule inhibitor of ASK1, a protein that promotes inflammation, apoptosis (cell death) and fibrosis in settings of oxidative stress. Oxidative stress can be increased in many pathological conditions including liver diseases such as NASH.

The STELLAR-4 study is a Phase 3, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of selonsertib in patients with compensated cirrhosis (F4) due to NASH. Eligible adults ages 18 to 70 years were randomized and received selonsertib 18 mg (n=354), selonsertib 6 mg (n=351) or placebo (n=172) for up to 240 weeks. Either selonsertib or placebo is being administered orally once daily. The primary endpoints of the study are a composite of the proportion of patients who achieve a ≥ 1-stage improvement in fibrosis according to the NASH CRN classification without worsening of NASH at week 48 and event-free survival at week 240 as assessed by time to the first clinical event. Further information about the clinical study can be found at www.clinicaltrials.gov.

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

Theravance Biopharma Announces First Patient Dosed in Registrational Phase 3 Study of Ampreloxetine (TD-9855) for the Treatment of Symptomatic Neurogenic Orthostatic Hypotension

 Theravance Biopharma, Inc. (NASDAQ: TBPH) ("Theravance Biopharma" or the "Company")  announced dosing of the first patient in a registrational Phase 3 clinical trial of ampreloxetine (TD-9855) in patients with symptomatic neurogenic orthostatic hypotension (nOH). Ampreloxetine is an investigational, once-daily norepinephrine reuptake inhibitor (NRI) in development for the treatment of patients with symptomatic nOH.

The Phase 3 study is a four-week, multi-center, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety and tolerability of ampreloxetine in approximately 188 patients with symptomatic nOH caused by primary autonomic failure associated with multiple system atrophy (MSA), Parkinson's disease (PD) and pure autonomic failure (PAF). Patients will be randomized to receive a single 10 mg dose of ampreloxetine or placebo once daily for four weeks. The primary endpoint of the study is change from baseline in dizziness severity, as measured by Orthostatic Hypotension Symptom Assessment (OHSA) Question #1 (OHSA #1, a measure of dizziness, lightheadedness or the sensation of being about to black out) at four weeks for ampreloxetine as compared to placebo. The study will evaluate additional efficacy assessments, as well as safety and tolerability measures.

"Given the limitations of currently available therapeutic options, we recognize a significant opportunity exists for a potentially safe and durable treatment for nOH. Positive four-week results achieved in our Phase 2 study provide the basis for advancing ampreloxetine into this registrational Phase 3 program," said Brett Haumann, MD, chief medical officer at Theravance Biopharma. "We are pleased to begin 2019 with this milestone, and in the near term we also anticipate dosing the first patient in the Phase 2b/3 study of TD-1473, our gut-selective JAK inhibitor, in patients with ulcerative colitis."

Theravance Biopharma previously announced positive four-week results from a Phase 2 clinical trial of ampreloxetine in patients with nOH. Findings showed that a majority of patients enrolled in the study's single ascending dose portion demonstrated durable improvements in nOH symptom severity as measured by OHSA #1. Patients treated in the extension phase of the study showed a mean symptom improvement of 2.4 points at four weeks. Importantly, mean symptom improvement was greatest (3.8 points) in nOH patients who reported dizziness symptoms (OHSA #1 > 4) at baseline, a pre-defined regulatory and clinical threshold that will be used to enroll patients in Phase 3. Additionally, ampreloxetine consistently increased systolic blood pressure (SBP), including clinically meaningful increases in standing SBP at the three-minute assessment at all time points on all weekly clinic visits. There were no drug-related serious adverse events reported, and ampreloxetine was generally well tolerated in the study.

http://www.dcchemicals.com/product_show-DC11076.html

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Theravance Biopharma Announces First Patient Dosed in Registrational Phase 3 Study of Ampreloxetine (TD-9855) for the Treatment of Symptomatic Neurogenic Orthostatic Hypotension