FDA Approves Zavzpret (zavegepant) Nasal Spray for the Acute Treatment of Migraine

Pfizer Inc. (NYSE: PFE)  announced the U.S. Food and Drug Administration (FDA)  approval of Zavzpret (zavegepant), the first and only calcitonin gene-related peptide (CGRP) receptor antagonist nasal spray for the acute treatment of migraine with or without aura in adults. In its pivotal Phase 3 study, Zavzpret was statistically superior to placebo on the co-primary endpoints of pain freedom and freedom from most bothersome symptom at two hours post-dose. The pivotal study also demonstrated pain relief as early as 15 minutes in a prespecified secondary endpoint versus placebo.

“The FDA approval of Zavzpret marks a significant breakthrough for people with migraine who need freedom from pain and prefer alternative options to oral medications,” said Angela Hwang, Chief Commercial Officer, President, Global Biopharmaceuticals Business, Pfizer. “Zavzpret underscores Pfizer’s commitment to delivering an additional treatment option to help people with migraine gain relief and get back to their daily lives. Pfizer will continue to build its migraine franchise to further support the billions of people worldwide impacted by this debilitating disease.”

The FDA approval is based on two pivotal randomized, double-blind, placebo-controlled studies that established the efficacy, tolerability and safety profiles of Zavzpret for the acute treatment of migraine. In these studies, Zavzpret was statistically superior to placebo on the co-primary endpoints of pain freedom (defined as a reduction of moderate or severe headache pain to no headache pain) and freedom from most bothersome symptom at two hours post-dose (defined as the absence of the self-identified most bothersome symptom). The pivotal Phase 3 study published in The Lancet Neurology found Zavzpret showed broad efficacy by also demonstrating statistically significant superiority to placebo across 13 of 17 prespecified secondary outcome measures, including early time point endpoints (e.g., 15 and 30-minute pain relief and return to normal function at 30 minutes), return to normal function at 2 hours, and durable efficacy endpoints (e.g., 2-24 and 2-48 hour sustained pain freedom and sustained pain relief). On the 14th endpoint, return to normal function at 15 minutes post-dose, the difference between Zavzpret and placebo was not significant. Consequently, in keeping with the trial’s statistical analysis plan, the remaining secondary endpoints were not formally tested.

“When a migraine hits, it has a significant negative impact on a person’s daily life,” said Kathleen Mullin, M.D., Associate Medical Director at New England Institute for Neurology & Headache. “Among my migraine patients, one of the most important attributes of an acute treatment option is how quickly it works. As a nasal spray with rapid drug absorption, Zavzpret offers an alternative treatment option for people who need pain relief or cannot take oral medications due to nausea or vomiting, so they can get back to normal function quickly.”

Zavzpret was well tolerated in clinical trials. The most common adverse reactions reported in at least 2% of patients treated with Zavzpret and at a frequency greater than placebo were taste disorders (includes dysgeusia and ageusia), nausea, nasal discomfort and vomiting. Zavzpret is contraindicated in patients with a history of hypersensitivity to zavegepant or to any of its components. Hypersensitivity reactions, including facial swelling and urticaria, have occurred with Zavzpret in clinical studies. 

 https://en.wikipedia.org/wiki/Zavegepant#/media/File:Zavegepant.svg

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

FDA Approves Zavzpret (zavegepant) Nasal Spray for the Acute Treatment of Migraine

FDA Approves Ryaltris (mometasone and olopatadine) Nasal Spray for Seasonal Allergic Rhinitis

In continuation of my update on olopatadine

Glenmark Pharmaceuticals Limited, announced the  FDA approval of its New Drug Application (NDA) for Ryaltris, an innovative, fixed- dose (metered), prescription, combination drug product nasal spray for the treatment of symptoms of Seasonal Allergic Rhinitis in adults and pediatric patients 12 years of age and older in the United States.

mometasone

Olopatadine,

The FDA's approval of Ryaltris™ represents a major milestone for Glenmark and clearly supports our efforts to bring innovative treatment options in our key therapeutic areas," said Robert Crockart, Chief Commercial Officer of Glenmark Pharmaceuticals Limited. "With this NDA approval, we look forward to bringing this new medicine to physicians and their patients for the treatment of symptoms of seasonal allergic rhinitis, including nasal and ocular symptoms."

Ryaltris™ will be marketed and distributed in the United States (US) by Hikma Specialty U.S.A., Inc., as part of its exclusive licensing agreement with Glenmark Specialty S.A (Switzerland).

Ryaltris is a metered, fixed-dose, aqueous suspension, prescription drug product nasal spray approved by the FDA for the treatment of symptoms associated with Seasonal Allergic Rhinitis. Each unit of Ryaltris™ nasal spray contains 665 mcg of olopatadine hydrochloride, a histamine-1(H1)-receptor inhibitor, and 25 mcg of mometasone furoate, a corticosteroid. The combination drug product nasal spray is indicated for the treatment of symptoms associated with seasonal allergic rhinitis in adults and pediatric patients 12 years of age and older. The safety and effectiveness of Ryaltris™ in pediatric patients younger than 12 years of age has not been established.

The recommended daily dose for Ryaltris is 2 sprays in each nostril twice daily.

Ryaltris will be marketed and distributed in the United States through their partner Hikma Specialty U.S.A. Inc., Columbus, OH.

Ryaltris has been approved and is marketed in Australia, the Czech Republic, Poland, Russia, South Africa, Ukraine, the United Kingdom, and Uzbekistan. In April 2021, Glenmark concluded the DCP regulatory procedure in Europe, enabling approval in 17 countries across EU and UK.

Glenmark has entered into commercial agreements with several partners around the world, including Menarini for the commercialization of Ryaltris™ in select EU markets, and with Bausch Health in Canada (where it is under review by Health Canada).

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

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

FDA Approves Ryaltris (mometasone and olopatadine) Nasal Spray for Seasonal Allergic Rhinitis

FDA Approves Trudhesa (dihydroergotamine mesylate) Nasal Spray for the Acute Treatment of Migraine

Impel NeuroPharma, Inc. (NASDAQ: IMPL),  announced  the U.S. Food and Drug Administration (FDA) approval of  Trudhesa™ (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) for the acute treatment of migraine with or without aura in adults. Trudhesa was previously known as INP104.

Using Impel’s proprietary Precision Olfactory Delivery (POD®) technology, Trudhesa gently delivers dihydroergotamine mesylate (DHE)—a proven, well-established therapeutic—quickly to the bloodstream through the vascular-rich upper nasal space.  Trudhesa bypasses the gut and potential absorption issues, offering rapid, sustained, and consistent symptom relief without injection or infusion, even when administered hours after the onset of a migraine attack.  The Commercial launch of Trudhesa is planned for early October 2021.

“We are delighted with the approval of Trudhesa and are proud to offer the millions of Americans with migraine a non-oral, acute treatment option that may provide rapid, sustained, and consistent relief, even when taken late into a migraine attack,” said Adrian Adams, Chairman and Chief Executive Officer of Impel NeuroPharma. “The approval of Trudhesa marks the culmination of more than a decade of research and advanced engineering to pair the proven efficacy of DHE with our innovative POD technology. We are grateful for all the patients and investigators who participated in our clinical trials and who were instrumental in bringing this needed advancement to the migraine community.”

The New Drug Application for Trudhesa included the results of the Phase 3, open-label, pivotal safety study, STOP 301, which is the largest longitudinal study ever conducted with DHE using nasal spray delivery.  More than 5,650 migraine attacks were treated over 24 or 52 weeks during the study. The primary objective of the study was to assess the safety and tolerability of Trudhesa. Exploratory objectives included efficacy assessments of migraine measures and a patient acceptability questionnaire. In the trial, Trudhesa was generally well tolerated and exploratory efficacy findings showed it provided rapid, sustained, and consistent symptom relief. Unlike some oral acute treatments that need to be taken within one hour of attack onset to be most effective, STOP 301 reported Trudhesa offered consistent efficacy even when taken late into a migraine attack. 

“Many of my patients need more from their migraine treatment, and Trudhesa offers a non-oral, fast-acting, reliable option that overcomes many current medication challenges,” said Stephanie J. Nahas-Geiger, MD, MSEd, Associate Professor in the Department of Neurology, and Program Director of the Headache Medicine Fellowship Program, Thomas Jefferson University. “Its upper nasal delivery circumvents the GI tract and common phenomena associated with migraine, such as nausea and gastroparesis, that can impact the effectiveness of oral treatments. And, importantly, it is a self-administered, single dose that can be taken anytime during a migraine attack, so patients don’t need to worry about missing the opportunity to benefit from using Trudhesa within a certain timeframe. I think patients will be very receptive to this treatment, because it pairs the long-proven benefits of DHE with a patient-friendly delivery system.”

There were no serious Trudhesa-related treatment-emergent adverse events (TEAEs) observed in the STOP 301 study and the majority of TEAEs were mild and transient in nature.  Some of the most frequently reported Trudhesa-related TEAEs (≥2%) during the entire 52-week study period were nasal congestion (17.8%), nausea (6.8%), nasal discomfort (6.8%), abnormal olfactory test (6.8%) and vomiting (2.7%).

In the STOP 301 study, patient-reported exploratory efficacy findings reported that more than a third of patients (38%) had pain freedom,  two-thirds (66%) had pain relief,  and more than half (52%) had freedom from their most bothersome migraine symptom  at two hours after their first dose of Trudhesa. For one in six patients (16%), pain relief started as early as 15 minutes.  Of patients who were pain free at two hours, 93 percent were still pain free at 24 hours,11 and 86 percent were still pain free through two days.  The great majority of patients (84%) reported that Trudhesa was easy to use  and preferred it over their current therapy.

“Migraine is a disease that impacts the whole body and is the second leading cause of disability,”  said Kevin Lenaburg, executive director, Coalition for Headache and Migraine Patients (CHAMP), which represents 12 national headache and migraine patient advocacy groups. “Historically there have not been enough effective treatments for treating migraine attacks, especially treatments that are not oral medicines, which can be challenging due to nausea, vomiting and other GI symptoms that can occur during a migraine. We welcome an important new treatment that combines the long-established efficacy of DHE with a non-oral, innovative delivery system that allows patients to self-administer wherever they are and at any point within a migraine attack.”

FDA Approves Nayzilam (midazolam) Nasal Spray to Treat Seizure Clusters

  

UCB announced   that the U.S. Food and Drug Administration (FDA) has approved a New Drug Application for the company’s newest anti-epileptic drug (AED) Nayzilam (midazolam) nasal spray CIV, a benzodiazepine indicated for the acute treatment of intermittent, stereotypic episodes of  frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 12 years of age and older. Nayzilam now provides patients and caregivers with the first and only FDA-approved nasal option for treating seizure clusters.  

It is estimated that more than 150,000 people in the U.S. with uncontrolled epilepsy also experience seizure clusters.2 Rescue treatment of seizure clusters is critical because when left untreated, seizure clusters can increase the risk of physical injury, neurological damage, prolonged seizures, and status epilepticus. Despite the impact of seizure clusters, many diagnosed patients may go untreated because currently available treatment options are not preferred.

Nayzilam is a short-term treatment for seizure clusters in patients with epilepsy. The nasal spray is designed as a single-use treatment that can be carried with a patient. Nayzilam allows for administration by a non-healthcare professional in patients actively seizing when and where a seizure cluster occurs. Nayzilam can provide value to patients who are experiencing these disruptive seizures.

“As global leaders in epilepsy, the approval of Nayzilam complements our already strong epilepsy portfolio, improving our ability to provide value to people living with poorly controlled seizures, and builds on our passion and expertise in this field. We are pleased to expand and diversify the solutions we can offer to the epilepsy community, providing an innovative and differentiated solution to help support management of seizure clusters,” said Jean-Christophe Tellier, Chief Executive Officer, UCB.

Nayzilam is the first new medication approved to treat seizure clusters in more than 20 years in the U.S. Its nasal delivery could provide significant value to patients who currently have limited treatment options.

“When a patient experiences seizure clusters, there is often significant impact on their overall quality of life, in addition to posing greater risks for increased emergency department related hospitalizations and more serious seizure emergencies,” said Dr. Steven S. Chung, MD, Executive Director and Program Chair of the Neuroscience Institute and Director of the Epilepsy Program at Banner – University Medical Center. “Further, as a neurologist specializing in epilepsy, treating seizure clusters today presents a challenging barrier for many patients. The availability of a new treatment option, such as Nayzilam, has potential to help improve the lives of patients and their families by providing another option for rescue care.”

https://www.drugbank.ca/drugs/DB00683

FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose

In continuation of my update on naloxone 

   

The first generic naloxone nasal spray to treat opioid overdose has received approval from the U.S. Food and Drug Administration.

Teva Pharmaceuticals' lifesaving product is also the first generic naloxone nasal spray approved for use by people without medical training. There was already a brand-name spray (Narcan) for emergency use by untrained people, such as family members and bystanders.

The need is urgent. On average, more than 130 Americans die every day from overdoses of opioids -- including prescription painkillers such as fentanyl, oxycodone (OxyContin), hydrocodone (Vicodin) and morphine, as well as illegal drugs such as heroin or drugs sold as heroin, the FDA said.

"In the wake of the opioid crisis, a number of efforts are underway to make this emergency overdose reversal treatment more readily available and more accessible," said Dr. Douglas Throckmorton, deputy center director for regulatory programs in the FDA's Center for Drug Evaluation and Research.

"In addition to this approval of the first generic naloxone nasal spray, moving forward we will prioritize our review of generic drug applications for naloxone," he added.

When someone overdoses on opioids, breathing may become shallow or stop completely, leading to death if no one intervenes. If administered quickly, naloxone can counter the effects within minutes.

Throckmorton said in an agency news release that the FDA is also helping drugmakers pursue approval of an over-the-counter naloxone product, and "exploring other ways to increase availability of naloxone products intended for use in the community."

The FDA is also considering whether naloxone should be routinely prescribed along with all or some opioid prescriptions in order to reduce the risk of overdose.

"Altogether, these efforts have the potential to put a vital tool for combating opioid overdose in the hands of those who need it most -- friends and families of opioid users, as well as first responders and community-based organizations," Throckmorton said.

Nearly 400,000 people in the United States died of opioid overdoses between 1999 and 2017, according to the U.S. Centers for Disease Control and Prevention.

"We're committed to working with other federal, state and local officials, as well as health care providers, patients and communities across the country to combat the staggering human and economic toll created by opioid abuse and addiction," Throckmorton said in the news release.

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

FDA Approves First Generic Naloxone Nasal Spray Against Opioid Overdose  

FDA Approves Tosymra (sumatriptan) Nasal Spray for Acute Treatment of Migraine

In continuation of my update on Tosymra (sumatriptan)

Dr. Reddy’s Laboratories Ltd. and its subsidiary, Promius Pharma, LLC today announced the approval of Tosymra (previously known as DFN-02) by the U.S. Food and Drug Administration (FDA). Tosymra is indicated for the acute treatment of migraine with or without aura in adults. Tosymra is the latest product to join the Promius Pharma acute migraine treatment portfolio. The company is working toward commercialization of this product.

“We are excited about the approval of Tosymra. This approval affirms our ability to develop well-differentiated products to meet the unmet needs of patients with migraine and HCPs treating them,” said G.V. Prasad, Co-Chairman and CEO, Dr. Reddy’s Laboratories.

According to Dr. Anil Namboodiripad, PhD, President, Promius Pharma, “Tosymra nasal spray is formulated using a proprietary novel excipient known as Intravail [®] to achieve blood levels similar to a 4-mg sumatriptan subcutaneous injection, resulting in rapid onset of action. Independent research shows that 26% to 40% of migraine patients are not optimally controlled with their current treatment.  For patients who suffer from the debilitating and disruptive effects of migraine, there continues to be a need for reliable and efficacious treatment options. At Promius, we are committed to developing new ways of improving patient experiences. Tosymra is a mist-like nasal spray that acts rapidly and is well tolerated.”

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

FDA Approves Tosymra (sumatriptan) Nasal Spray for Acute Treatment of Migraine

Nasal spray delivers new type of depression treatment -- ScienceDaily

Nasal spray delivers new type of depression treatment

Heat in Chili Peppers Can Ease Sinus Problems, Research Shows

In continuation of my update on the usefulness of   Casaicin...

We know that, Capsicum annum contains capsaicin, which is the main component of chili peppers and produces a hot sensation. Capsaicin is also the active ingredient in several topical medications used for temporary pain relief. It is approved for use by the U.S. Food and Drug Administration and is available over the counter.

Now researchers lead by  Jonathan A. Bernstein of University of Cincinnati College of Medicine, Cincinnati, Ohio, have come up with an interesting finding about Capsicum annum.  As per the claim by the researchers a nasal spray containing an ingredient derived from hot chili peppers (Capsicum annum) may help people "clear up" certain types of sinus inflammation. Researchers add that, study which showed that participants who used a nasal spray with Capsicum reported a faster onset of action or relief, on average within a minute of using the spray, than the control group and the spray is safe  and effective on non-allergic rhinitis.

Interestingly, this is the first controlled trial where capsaicin was able to be used on a continuous basis to control symptoms. It is considered a significant advance, because of the fact  that in  the previous trials the ingredient was too hot to administer without anesthesia.

Ref : http://www.annallergy.org/article/S1081-1206%2811%2900383-8/abstract