pitolisant

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

PLYMOUTH MEETING, PA, February 12, 2019 — Harmony Biosciences, LLC (Harmony), announced today 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.
About Narcolepsy

Narcolepsy is a rare, chronic, debilitating neurologic disorder of sleep-wake state instability that impacts up to 200,000 Americans and is primarily characterized by EDS, cataplexy, and other manifestations of REM sleep dysregulation, which intrude into wakefulness. In most patients, it is caused by the loss of hypocretin, a neuropeptide in the brain that supports sleep-wake state stability. This disorder affects men and women equally, with typical symptom onset in adolescence or young adulthood; however, it can take up to a decade to be properly diagnosed. Narcolepsy can cause significant burden for patients and their families, affecting their ability to perform routine tasks, limit achievement at school and work, impact social relationships and cause impairment in overall quality of life.
About Cataplexy

Cataplexy is one of several symptoms of narcolepsy that represent elements of REM sleep state intruding into wakefulness, characterized by sudden temporary loss of muscle tone. Cataplexy can be subtle, such as drooping of eyelids, or severe, such as knee buckling or total body collapse. Often times, symptoms of cataplexy may go unrecognized because of the subtle nature of the symptoms in some patients, variability of how cataplexy is expressed, and/or lack of patient complaints or physician recognition of the symptoms as manifestations of cataplexy. This symptom of narcolepsy can often cause significant impact on a person’s ability to carry out normal daily functions. Up to two-thirds of all patients with narcolepsy have cataplexy (known as Type 1 narcolepsy); cataplexy is one of the most debilitating symptoms of this chronic, rare neurologic disorder.
Harmony Biosciences, LLC

Harmony Biosciences, LLC, is a private biopharmaceutical company headquartered in Plymouth Meeting, PA. The company was established in October 2017 with a vision to provide novel treatment options for people living with rare and orphan diseases, with an emphasis on central nervous system disorders, starting with patients living with narcolepsy. Harmony is committed to advancing the understanding of narcolepsy and providing information and resources to individuals who live with, and healthcare professionals who treat patients with, this disorder. For 

lemborexant

lemborexant
New Drug Application for Insomnia Disorder Treatment Lemborexant Submitted in the United States


TOKYO and STAMFORD, Conn. – January 15, 2019 – Eisai Co., Ltd. (CEO: Haruo Naito, “Eisai”) and Purdue Pharma L.P. (President and CEO: Craig Landau, MD, “Purdue Pharma”) today announced that a new drug application has been submitted to the U.S. Food and Drug Administration (FDA) for lemborexant, an investigational agent for sleep-wake regulation, seeking approval for the treatment of insomnia, a sleep-wake disorder.
This application was based on the results of two pivotal Phase 3 clinical studies in patients with insomnia, SUNRISE 1 (Study 304) and SUNRISE 2 (Study 303), enrolling approximately 2,000 patients, as well as important safety studies, including assessment of postural stability after middle-of-the-night awakening and a next-morning driving study. SUNRISE 1, a one-month, double-blind, placebo-controlled study, included the first ever Phase 3 head-to-head comparison versus zolpidem ER and objectively assessed sleep parameters (time to sleep onset, sleep efficiency, and wake after sleep onset) resulting in the largest (objective) polysomnography dataset collected to date in patients with insomnia. SUNRISE 2 was a 12-month study and subjectively assessed for ability to fall asleep and stay asleep based on patient self reports (sleep diaries).
Lemborexant, which acts on the orexin neurotransmitter system and is believed to regulate sleep and wake by dampening wakefulness without impeding the ability to awaken to external stimuli, is being jointly developed by Eisai and Purdue Pharma for the treatment of multiple sleep-wake disorders, including insomnia disorder. In addition to the treatment of insomnia disorder, a Phase 2 clinical study of lemborexant in patients with irregular sleep-wake rhythm disorder and mild to moderate Alzheimer's dementia is underway. Information about ongoing clinical studies is available at clinicaltrials.gov.
Eisai and Purdue Pharma are striving to address new unmet medical needs and to improve the lives of patients and their families.
This release discusses investigational uses of an agent in development and is not intended to convey conclusions about efficacy or safety. There is no guarantee that such an investigational agent will successfully complete clinical development or gain health authority approval.
 About Lemborexant

Lemborexant is a novel investigational small molecule compound, discovered and developed by Eisai in-house scientists, that inhibits orexin signaling by binding competitively to both orexin receptor subtypes (orexin receptor 1 and 2). In individuals with normal daily sleep-wake rhythms, orexin signaling is believed to promote periods of wakefulness. In individuals with sleep-wake disorders, it is possible that orexin signaling which regulates wakefulness is not functioning normally, suggesting that inhibiting inappropriate orexin signaling may enable initiation and maintenance of sleep.
About SUNRISE 1 (Study 304)

SUNRISE 11 was a multicenter, randomized, double-blind, placebo-controlled, active comparator, parallel-group study evaluating the efficacy and safety of lemborexant in 1,006 male or female adult patients 55 years and older (45 percent of patients were 65 years and older) with insomnia disorder conducted in North America and Europe. SUNRISE 1 included a pre-randomization phase of up to 35 days (including a two-week placebo run-in period) and a randomization phase comprised of a 30-day treatment period and a minimum two-week period without treatment prior to the end-of-study visit. In this study, patients were randomized to receive placebo or one of three treatment regimens (lemborexant 5 mg, lemborexant 10 mg, zolpidem ER 6.25 mg). The primary objective for SUNRISE 1 was to demonstrate using polysomnography that lemborexant at either the 5 mg or 10 mg dose is superior to placebo on objective sleep onset, as measured by latency to persistent sleep after the last two nights of one month of treatment. Key secondary objectives included change from baseline in sleep efficiency and wake after sleep onset (WASO) for both lemborexant doses compared to placebo, and WASO in the second half of the night (WASO2H) for both lemborexant doses compared to zolpidem ER, each after the last two nights of one month of treatment.
About SUNRISE 2 (Study 303)

SUNRISE 22 was a 12-month multicenter, global, randomized, controlled, double-blind, parallel-group study of the efficacy and safety of lemborexant in 949 male or female adult participants 18 to 88 years of age with insomnia disorder. SUNRISE 2 included a pre-randomization phase of up to 35 days (including a two-week placebo run-in period) and a randomization phase comprised of a six-month placebo-controlled treatment period, a six-month period of only active treatment and a two-week period without treatment prior to the end-of-study-visit. In this study, during the placebo-controlled treatment period, patients were randomized to receive placebo or one of two treatment regimens (lemborexant 5 mg or 10 mg). During the active-only treatment period, patients who received placebo during the first period were re-randomized to receive lemborexant 5 mg or 10 mg. Patients who received active treatment during the first period continued on the treatment to which they were originally randomized. The primary objective was to determine the efficacy of lemborexant 5 mg and 10 mg compared to placebo on patient-reported (subjective) sleep onset latency after six months of treatment. Key secondary endpoints were mean change from baseline in subjective sleep efficiency and subjective wake after sleep onset (sWASO) for lemborexant 5 mg and 10 mg compared to placebo after six months of treatment.
About Sleep Disorders

Population studies show that sleep disorders affect many more people worldwide than previously thought.3 Insomnia disorder is the most common sleep disorder affecting approximately 30 percent of the adult population worldwide.3,4 Insomnia disorder is characterized by difficulty falling asleep, staying asleep or both, despite an adequate opportunity to sleep, which can lead to daytime consequences such as fatigue, difficulty concentrating and irritability.5,6
Sleeping well is essential for good health, including brain health. Poor sleep is associated with a wide range of health consequences, including an increased risk of hypertension, accidental injury, diabetes, obesity, depression, heart attack, stroke and dementia, as well as adverse effects on mood and behavior.5,7
Experimental studies in animals and humans provide evidence of associations between sleep and disease risk factors, diseases and mortality.8 Studies suggest an optimal sleep duration between seven and eight hours.9
Women are 1.4 times more likely than men to suffer from insomnia.10 Older adults also have higher prevalence of insomnia; aging is often accompanied by changes in sleep patterns, including disrupted sleep, frequent waking and early waking, that can lead to less sleep time.11
About Eisai Co., Ltd

Eisai Co., Ltd. is a leading global research and development-based pharmaceutical company headquartered in Japan. We define our corporate mission as "giving first thought to patients and their families and to increasing the benefits health care provides," which we call our human health care (hhc) philosophy. With over 10,000 employees working across our global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to realize our hhc philosophy by delivering innovative products in various therapeutic areas with high unmet medical needs, including Neurology and Oncology.
Furthermore, we invest and participate in several partnership-based initiatives to improve access to medicines in developing and emerging countries.
For 

Opioids Prescribed in Hospital Often Tied to Long-Term Use

 People given opioids for the first time in the hospital are likely to continue getting them for months after, a new study reports.
A University of Pittsburgh team found that those first-timers are twice as likely to receive more opioids after discharge than patients who were not given opioids (such as oxycodone) in the hospital.
"I was surprised by the level of opioid prescribing to patients without a history of opioid use," said lead author Julie Donohue, a professor of health policy and management.
Nearly half of patients admitted to the hospital are given opioids, she said. And while doctors are prescribing fewer opioids outside the hospital, "we didn't see that in inpatient prescribing," she added in a university news release.
For the study, Donohue and her colleagues studied electronic health records of more than 191,000 patients who had not been prescribed opioids during the year prior to their hospitalization.
Opioids were prescribed to 48% of these patients for just over two-thirds of their hospital stay, on average, the study found. Three months later, 6% of those patients were still being prescribed opioids, compared with 3% of others.
Nearly 8% of those given opioids within 12 hours of discharge were still taking them three months later, compared with 4% of those who had not used them in 24 hours before leaving the hospital, the findings showed.
Non-opioid painkillers, such as ibuprofen (Advil, Motrin), aspirin or naproxen (Aleve), were rarely tried first -- about 8% of the time for some conditions, the researchers found.
"Inpatient opioid use has been something of a black box," Donohue said. "And, while our study could not assess the appropriateness of opioid administration, we identified several practices -- low use of non-opioid painkillers, continuous use of opioids while hospitalized, opioid use shortly before discharge -- which may be opportunities to reduce risk of outpatient opioid use, and warrant further study."
The report was published June 17 in the Annals of Internal Medicine.

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Compared with insulin glargine, initial injectable therapy with a combination of insulin degludec and liraglutide aids achievement of blood glucose goals for a longer period of time in patients with uncontrolled type 2 diabetes on oral antidiabetic drugs, according to a study published online June 9 in The Lancet Diabetes & Endocrinology to coincide with the annual meeting of the American Diabetes Association, held from June 7 to 11 in San Francisco.

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Zygel

Zynerba Pharmaceuticals Receives Fast Track Designation for Zygel for the Treatment of Behavioral Symptoms Associated with Fragile X Syndrome (FXS)

Devon, PA, May 6, 2019 — Zynerba Pharmaceuticals, Inc. (NASDAQ:ZYNE), the leader in innovative pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders, today announced that the U.S. Food and Drug Administration (FDA) has
granted Fast Track Designation for the Company’s lead development candidate Zygel™ (ZYN002 CBD gel) for treatment of behavioral symptoms associated with Fragile X Syndrome (FXS). FDA’s Fast Track program is designed to facilitate the development of drugs intended to treat serious conditions and fill unmet medical needs, and can lead to expedited review by FDA in order to get new important drugs to the patient earlier.
“The FDA’s decision to grant Fast Track Designation for Zygel underscores the significance and severity of the unmet medical need that exists for patients living with Fragile X Syndrome and their caregivers,” said Armando Anido, Chairman and Chief Executive Officer of Zynerba. “We believe that Zygel has the potential to be the first treatment indicated to directly address the core behavioral symptoms of this syndrome, and we look forward to working closely with the FDA to obtain approval to market Zygel as soon as possible.”
Zynerba is conducting a pivotal trial to assess the efficacy and safety of Zygel as treatment for the behavioral symptoms of FXS in pediatric and adolescent patients (three through 17 years of age). Zygel is a pharmaceutically-manufactured CBD formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled transdermal drug delivery into the bloodstream.
About Fast Track Designation

Fast Track Designation is intended to facilitate development and expedite review of drugs to treat serious or life-threatening conditions so that a product can reach the market expeditiously. A drug that is intended to treat a serious or life-threatening condition that demonstrates the potential to address an unmet medical need may qualify for Fast Track designation. Features of this designation include opportunities for frequent interactions with the review team. These include meetings with the FDA to discuss items such as study design, extent of safety data required to support approval, dose-response concerns, accelerated approval, the structure and content of an NDA, and other critical issues. In addition, such a product could be eligible for priority review if supported by clinical data at the time of NDA.
About Fragile X Syndrome (FXS)

Fragile X syndrome is a rare genetic developmental disability that is the leading known cause of both inherited intellectual disability and autism spectrum disorder, affecting 1 in 3,600 to 4,000 males and 1 in 4,000 to 6,000 females. It is the most common inherited intellectual disability in males and a significant cause of intellectual disability in females. FXS is caused by a mutation in the Fragile X Mental Retardation gene (FMR1) located on the X chromosome and leads to dysregulation of the endocannabinoid pathway including the reduction in endogenous cannabinoids (2-AG and anandamide). The disorder negatively affects synaptic function, plasticity and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. In the US, there are about 71,000 patients suffering with FXS.
About Zygel

Zygel (CBD gel) is the first and only pharmaceutically-manufactured CBD formulated as a patent-protected permeation-enhanced clear gel, designed to provide controlled drug delivery into the bloodstream transdermally (i.e. through the skin). Recent studies suggest that FXS and other neuropsychiatric conditions may be associated with a disruption in the endocannabinoid (EC) system. Clinical and anecdotal data suggest that CBD may modulate the EC system and improve certain core social and behavioral symptoms, including social avoidance (prefers isolation from others, prefers solitary activities, avoids new social activities), irritability (aggressive to others, tantrums/outbursts, and stubbornness), and social unresponsiveness/lethargy (lack of attention/interaction, inactive/lack of movement and can resist physical contact).
Enrollment is ongoing in the multi-national, randomized, double blind placebo controlled Clinical study of Cannabidiol (CBD) in Children and Adolescents with Fragile X (CONNECT-FX), a pivotal clinical trial of ZYN002 in FXS (https://www.connectfxtrial.com/); topline data from CONNECT-FX are expected in the second half of 2019. Additionally, Zynerba expects topline data from its Phase 2 Open Label Study to Assess the Safety and Efficacy of ZYN002 Administered as a TransdermalGel to Children and Adolescents with Developmental and Epileptic Encephalopathy (BELIEVE 1) clinical trial in the third quarter of 2019. Zynerba has also initiated a Phase 2 study of Zygel in Autism Spectrum Disorder, with data expected in the first half of 2020.
About Zynerba Pharmaceuticals, Inc.

Zynerba Pharmaceuticals is the leader in pharmaceutically-produced transdermal cannabinoid therapies for rare and near-rare neuropsychiatric disorders. We are committed to improving the lives of patients and their families living with severe, chronic health conditions including Fragile X Syndrome, Autism Spectrum Disorder, 22q11.2 Deletion Syndrome, and a heterogeneous group of rare and ultra-rare epilepsies known as developmental and epileptic encephalopathies. Learn more at www.zynerba.com and follow us on Twitter at @ZynerbaPharma.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,” “proposed,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from the Company’s current expectations. For example, there can be no guarantee that the Company will obtain approval for Zygel from the U.S. Food and Drug Administration (FDA) or foreign regulatory authorities; even if Zygel is approved, the Company may not be able to obtain the label claims that it is seeking from the FDA. Management’s expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the Company’s cash and cash equivalents may not be sufficient to support its operating plan for as long as anticipated; the Company’s ability to obtain additional funding to support its clinical development programs; the results, cost and timing of the Company’s clinical development programs, including any delays to such clinical trials relating to enrollment or site initiation; clinical results for the Company’s product candidates may not be replicated or continue to occur in additional trials and may not otherwise support further development in a specified indication or at all; actions or advice of the FDA and foreign regulatory agencies may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional clinical trials; the Company’s ability to obtain and maintain regulatory approval for its product candidates, and the labeling under any such approval; the Company’s reliance on third parties to assist in conducting pre-clinical and clinical trials for its product candidates; delays, interruptions or failures in the manufacture and supply of the Company’s product candidates the Company’s ability to commercialize its product candidates; the size and growth potential of the markets for the Company’s product candidates, and the Company’s ability to service those markets; the Company’s ability to develop sales and marketing capabilities, whether alone or with potential future collaborators; the rate and degree of market acceptance of the Company’s product candidates; and the Company’s expectations regarding its ability to obtain and adequately maintain sufficient intellectual property protection for its product candidates. This list is not exhaustive and these and other risks are described in the Company’s periodic reports, including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the Securities and Exchange Commission and available at www.sec.gov. Any forward-looking statements that the Company makes in this press release speak only as of the date of this press release. The Company assumes no obligation to update forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
Source: Zynerba Pharmaceuticals, Inc.

Has America's Fight Against HIV Stalled?

 The battle against new HIV infections has lost some steam in recent years, a new report shows.
After about five years of significant declines, the number of new HIV infections began to level off in 2013, at about 39,000 infections per year, the U.S. Centers for Disease Control and Prevention found.
Why the slowing? Effective HIV prevention and treatments are not reaching those who could most benefit, according to the CDC.
These shortfalls in prevention and treatment are most glaring in rural areas and in the South, and they disproportionately affect blacks and Hispanics.
The report found that HIV infections declined in some groups, but increased in others. From 2010 to 2016, annual HIV infections were stable among gay and bisexual men, who continue to account for the largest portion (about 70 percent) of new infections.
But infection trends varied by race, ethnicity and age.
Infections remained stable among all black gay and bisexual men, increased 30 percent among all Hispanic gay and bisexual men, and fell 16 percent among all white gay and bisexual men.
Infections decreased more than 30 percent among black gay and bisexual males aged 13 to 24, and remained stable among Hispanic gay and bisexual males aged 13 to 24. Meanwhile, they rose 65 percent among black and Hispanic gay and bisexual males aged 25 to 34.
Infections fell 17 percent among heterosexual men and women combined, including a 15 percent decrease among heterosexual black women.
Infections decreased 30 percent among people who inject drugs, but appear to have stabilized in more recent years, according to the report released Wednesday.
"After a decades-long struggle, the path to eliminate America's HIV epidemic is clear," said Dr. Eugene McCray, director of CDC's Division of HIV/AIDS Prevention.
"Expanding efforts across the country will close gaps, overcome threats and turn around troublesome trends," he said in an agency news release.
In his State of the Union address to the nation on Feb. 5, President Donald Trump called for support of a national plan to: diagnose HIV as early as possible; treat HIV rapidly and effectively; protect at-risk people with proven preventive measures, including a daily pill to prevent HIV infection; and respond rapidly to growing clusters of HIV infections.
The initiative is designed to accelerate use of these strategies in the 48 U.S. counties with the highest HIV burden, as well as in Washington, D.C.; San Juan, Puerto Rico; and seven states with a disproportionate rural HIV burden.
Intensified local efforts have already produced promising results, according to the CDC. Public health officials in New York City and Washington, D.C., set plans in motion to eliminate their local HIV epidemics -- and they seemed to have worked. From 2010 to 2016, new HIV infections decreased about 23 percent in New York City, while they dropped about 40 percent in Washington, D.C.
The national goal under Trump's proposal is to reduce new HIV infections by 90 percent over 10 years.
"We have an historic opportunity to improve the precision of prevention," said Dr. Jonathan Mermin, director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention.
"This infusion of resources will finally relegate America's HIV epidemic to the pages of history," Mermin added.