FDA Approval of Xofluza (baloxavir marboxil) for High Risk of Developing Influenza-Related Complications

 Genentech, a member of the Roche Group,  announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for Xofluza™ (baloxavir marboxil) for the treatment of acute, uncomplicated influenza, or flu, in people 12 years of age and older who have been symptomatic for no more than 48 hours and who are at high risk of developing flu-related complications. Xofluza is a first-in-class, one-dose oral medicine with a novel proposed mechanism of action that inhibits polymerase acidic endonuclease, an enzyme essential for viral replication.

"With the flu season rapidly approaching, we can now offer Xofluza as the first and only FDA-approved treatment option indicated specifically for those at high risk of flu complications," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “People with chronic conditions such as asthma, heart disease and diabetes are at higher risk of developing serious complications from the flu, so it is critical that these patients speak with their healthcare providers about possible treatment at the first signs and symptoms of the disease.”

The flu has the potential to cause a variety of complications, ranging from sinus or ear infections to more serious complications such as pneumonia. This expanded indication for Xofluza was approved based on results from the Phase III CAPSTONE-2 study of a single dose of 40 mg or 80 mg of Xofluza compared to oseltamivir (75 mg twice daily for five days), or placebo in people 12 years of age or older who met CDC criteria for being at high risk of complications from the flu. Xofluza significantly reduced the time to improvement of flu symptoms compared to placebo, including in people infected with the flu type B virus. Adverse events reported in at least 1% of adult and adolescent subjects treated with Xofluza included diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%) and headache (1%).

Xofluza is currently approved in several countries for the treatment of flu types A and B. In October 2018, Xofluza was first approved by the FDA for the treatment of acute, uncomplicated flu in otherwise healthy people 12 years of age and older who have been symptomatic for no more than 48 hours, representing the first new antiviral to treat the flu in the U.S. in 20 years.

About CAPSTONE-2

CAPSTONE-2 is a Phase III, multicenter, randomized, double-blind study that evaluated a single dose of Xofluza compared with placebo and oseltamivir in people 12 years of age or older who are at a high risk of complications from the flu. The Centers for Disease Control and Prevention (CDC) defines people at high risk of serious flu complications as those who have conditions such as asthma, chronic lung disease, diabetes, heart disease, morbid obesity or adults 65 years of age or older. The study was conducted globally by Shionogi & Co., Ltd.

Participants enrolled in the study were randomly assigned to receive a single dose of 40 mg or 80 mg of Xofluza, placebo or 75 mg of oseltamivir twice a day for five days. The primary objective of the study was to evaluate the efficacy of a single dose of Xofluza compared with placebo by measuring the time to improvement of flu symptoms. Key findings from the study found that:

Xofluza significantly reduced the time to improvement of flu symptoms versus placebo in people at high risk of complications from the flu (median time 73 hours versus 102 hours; p<0.001). Similar efficacy results were seen between Xofluza and oseltamivir in relation to duration of symptoms (median time 73 hours versus 81hours). In subjects infected with type B virus, the median time to improvement of flu symptoms was shorter in the Xofluza group compared to the placebo group (75 hours versus 101 hours respectively). Adverse events reported in at least 1% of adult and adolescent subjects treated with Xofluza included diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%) and headache (1%). Xofluza was well-tolerated and no new safety signals were identified.

About Xofluza ™ (baloxavir marboxil)

Xofluza is a first-in-class, one-dose oral medicine with a novel proposed mechanism of action that has demonstrated efficacy in a wide range of influenza viruses, including in vitro activity against oseltamivir-resistant strains and avian strains (H7N9, H5N1) in non-clinical studies. Unlike other currently available antiviral treatments, Xofluza is the first in a new class of antivirals designed to inhibit the cap-dependent endonuclease protein, which is essential for viral replication.

FDA Approves Second Drug, Vyleesi, to Help Women With Low Libido

In continuation of my update on bremelanotide

The U.S. Food and Drug Administration on Friday gave its approval to Vyleesi, the second medication so far approved to help women with low sexual desire.

In a news release, the FDA said that Vyleesi (bremelanotide) is a drug that would be administered by injection prior to having sex.

It's been specifically approved for premenopausal women with a condition known as acquired, generalized hypoactive sexual desire disorder (HSDD).

"There are women who, for no known reason, have reduced sexual desire that causes marked distress, and who can benefit from safe and effective pharmacologic treatment," said Dr. Hylton Joffe, who directs the FDA's Center for Drug Evaluation and Research's Division of Bone, Reproductive and Urologic Products.

"Today's approval provides women with another treatment option for this condition," Hylton said in the news release.

According to the agency, HSDD is not caused by any medical or psychiatric condition, relationship issues or drug side effects.

Instead, women with HSDD have "previously experienced no problems with sexual desire," the FDA said. "Generalized HSDD refers to HSDD that occurs regardless of the type of sexual activity, situation or partner."

The exact way in which Vyleesi helps stimulate sexual desire remains unclear, but it works on melanocortin receptors on cells, the FDA said.

The drug is injected under the skin of the abdomen or thigh at least 45 minutes prior to a sexual encounter, although the best timeframe for dosing could vary from user to user.

Side effects can occur, the FDA added, and include nausea and vomiting, flushing, injection site reactions and headache. Nausea was especially common, affecting 40% of users in the clinical study that led to approval.

That study involved 1,247 premenopausal women with HSDD who received Vyleesi or a placebo in one of two 24-week trials.

"In these trials, about 25% of patients treated with Vyleesi had an increase of 1.2 or more in their sexual desire score (scored on a range of 1.2 to 6.0, with higher scores indicating greater sexual desire) compared to about 17% of those who took placebo," the FDA noted.

Still, the overall benefit was not large. "There was no difference between treatment groups in the change from the start of the study to end of the study in the number of satisfying sexual events. Vyleesi does not enhance sexual performance," the FDA said.

And there was one other caveat: Vyleesi can hike blood pressure, so people with heart disease or high blood pressure should not take it, the FDA said.

Vyleesi should also not be taken by anyone who is also taking the drug naltrexone, used to combat opioid dependency, because Vyleesi reduces naltrexone's effectiveness.

Vyleesi is not the first drug approved to enhance flagging libido in women. In 2015 the FDA approved Addyi (flibanserin) for the purpose, but the drug did not become widely used because it cannot be taken with alcohol and only certain certified health care providers are allowed to prescribe it.

According to CNN, Vyleesi's maker, AMAG Pharmaceuticals, said the new drug will not be available until September, and pricing and reimbursement have yet to be determined.

One expert in female sexual health said it remains to be seen how widely Vyleesi will be used.

"Female sexual dysfunction is more complicated in some ways than male sexual dysfunction, so it's more difficult to treat," Dr. Nicole Cirino, co-director of the Menopause and Sexual Therapy Clinic at Oregon Health and Science University's Center for Women's Health, told CNN. She had no role in Vyleesi's development.

Cirini suspects Vyleesi probably will not be the first option women with HSDD turn to, but it might prove a useful adjunct to standard psychotherapy and Addyi.

Vyleesi, like Addyi, probably won't be overprescribed, Cirino added. When Addyi was introduced, there were concerns "that doctors would just be prescribing this medication to anybody that came in saying that they were having an issue with their libido," she said. "And I think we have to give physicians more credit than that. In fact, that didn't happen at all."

Still, Vyleesi could help some women, Cirino said

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

FDA Approves Secuado (asenapine) Transdermal System for the Treatment of Adults with Schizophrenia

Noven Pharmaceuticals, Inc., a wholly-owned subsidiary of Hisamitsu Pharmaceutical Co., Inc., today announced the U.S. Food and Drug Administration (FDA) has approved Secuado (asenapine see below pic)) transdermal system, the first-and-only transdermal patch formulation for the treatment of adults with schizophrenia.

“As people living with schizophrenia cycle through treatments their therapeutic options narrow, leaving them and their caregivers looking for new treatment options,” said Leslie Citrome, M.D., M.P.H., Clinical Professor of Psychiatry and Behavioral Sciences, New York Medical College. “In addition to offering a new delivery option, transdermal patches can also provide caretakers and healthcare providers with a non-intrusive, visual confirmation that a treatment is being utilized.”

The once-daily transdermal drug delivery system (TDDS) provides sustained concentrations during wear time (24 hours)2 of the atypical antipsychotic drug asenapine, a well-established treatment for schizophrenia. A transdermal patch may help to mitigate some of the challenges patients face with the management of their schizophrenia.2

“There is an enormous unmet need for new types of schizophrenia treatments, and Noven is committed to giving people living with this devastating disease and their family members new options that may help them effectively manage their symptoms,” said Dr. Naruhito Higo, Chairman and Chief Executive Officer, Noven Pharmaceuticals, Inc. “We commend the FDA on the approval of Secuado and look forward to bringing it to market in the U.S. as soon as possible so people living with schizophrenia have a transdermal delivery option for asenapine treatment.”

In the international, Phase 3, double-blind, placebo-controlled study, Secuado achieved the primary endpoint of statistically significant improvement from baseline in the change of the total Positive and Negative Syndrome Scale (PANSS) compared to placebo at week six. Efficacy and safety were assessed during the six-week treatment period in 616 adults living with schizophrenia. Additionally, Secuado demonstrated statistically significant improvement in Clinical Global Impression-Severity (CGI-S) scores, the key secondary endpoint of the Phase 3 study.

The systemic safety profile of Secuado was consistent with what is known for sublingual asenapine.1 The most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain.1

What is Secuado?

Secuado is a prescription medicine used to treat adults with schizophrenia. Secuado is a transdermal system (patch) you apply to your skin. It is not known if Secuado is safe and effective in children less than 18 years of age with schizophrenia.

IMPORTANT SAFETY INFORMATION

Secuado may cause serious side effects, including:

• Increased risk of death in elderly people with dementia-related psychosis. Medicines like Secuado can raise the risk of death in elderly people who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Secuado is not approved for the treatment of people with dementia-related psychosis.
• Stroke (cerebrovascular problems) in elderly people with dementia-related psychosis that can lead to death.
• Neuroleptic Malignant Syndrome (NMS): a serious condition that can lead to death. Immediately remove the patch. Call your healthcare provider or go to the nearest hospital emergency room right away if you have some or all of the following: high fever, confusion, stiff muscles, increased sweating and changes in your breathing, heart rate and blood pressure.
• Uncontrolled body movements (tardive dyskinesia). Secuado may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop taking Secuado. Tardive dyskinesia may also start after you stop taking Secuado.
• Problems with your metabolism such as:
  • High blood sugar (hyperglycemia) and diabetes. Increases in blood sugar can happen in some people who take Secuado.
    Call your healthcare provider if you have any of these symptoms of high blood sugar during treatment with Secuado:
    • Feel very thirsty or very hungry
    • Feel sick to your stomach
    • Feel weak or tired
    • Need to urinate more than usual
    • Feel confused, or your breath smells fruity
  • Increased fat levels (cholesterol and triglycerides) in your blood
  • Weight gain. You and your healthcare provider should check your weight regularly during treatment with Secuado.
• Allergic reactions. You may observe rash, decreased blood pressure or a fast heart rate.
• Decreased blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.
• Falls. Secuado may make you sleepy or dizzy, may cause a decrease in your blood pressure when changing position, and can slow your thinking which may lead to falls.
• Low white blood cell count. Your healthcare provider may do blood tests during the first few months of treatment with Secuado.
• Irregular heartbeat or a heartbeat that does not feel normal (QT prolongation)
• Increased prolactin levels in your blood (hyperprolactinemia). Your healthcare provider may do blood tests to check your prolactin levels during treatment with Secuado.
• Seizures (convulsions)
• Impaired thinking and motor skills. Use caution when operating heavy machinery when using Secuado.
• Problems controlling your body temperature so that you feel too warm
• Difficulty swallowing
• External heat. Avoid exposing Secuado to direct external heat sources such as hair dryers, heating pads, electric blankets, heated water beds, etc.
• Application site reactions. Increased skin irritation may occur if Secuado is applied for a longer period than instructed or if the same application site is used repeatedly. Use a different application site each day to decrease skin reactions. If skin reactions continue or spread beyond the application site, tell your healthcare provider. Symptoms of application site reactions may include:
• Redness
• Itching
• Irritation
• Pimple-like raised skin
• Pain of the skin
• Swelling
• More 

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

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