Selinexor Offers Hope Against a Tough-to-Treat Blood Cancer

In continuation of my update on Selinexor

Patients with a form of blood cancer known as multiple myeloma who haven't responded to other therapies might have a new weapon against the disease, researchers say.

A drug called selinexor appeared to help patients with the blood and bone marrow cancer, according to a clinical trial involving 122 people.

"This study proved that a novel, first-in-class drug with a new mechanism of action can kill a patient's cancer cells," said study senior author Dr. Sundar Jagannath. He directs the multiple myeloma program at the Tisch Cancer Institute at Mount Sinai in New York City.

Selinexor also "worked in patients who had exhausted every other treatment and who would have been placed on hospice care otherwise," Jagannath said in a hospital news release.

In the trial, which was funded by the drug's maker, Karyopharm, patients at centers in the United States and Europe received a combination therapy of two pills, selinexor and the standard anti-cancer medicine dexamethasone.

As reported in the Aug. 22 issue of the New England Journal of Medicine, nearly 40% of the patients showed at least a minimal response to the therapy within one or two months. There were "significant" responses in more than a quarter of the patients, the researchers said, and two patients had their cancers go into complete remission.

As the team explained, selinexor works in a new way to fight myeloma, blocking a key mechanism in cancer cell growth and causing the cell to die.

Although the drug caused no toxicity to organs, there were side effects for some patients. These included low blood counts without bleeding, nausea, vomiting, lack of appetite or fatigue.

The U.S. Food and Drug Administration had already approved selinexor in early July to treat patients with multiple myeloma resistant to multiple therapies.

"This study is meaningful for patients with multiple myeloma who haven't had success on multiple other therapies," said study first author Dr. Ajai Chari, director of clinical research in the multiple myeloma program at the Tisch Cancer Institute.

"An increasing number of patients have resistance to the standard drugs used in the treatment of multiple myeloma, and the overall survival in these patients is short, sometimes less than three months," Chari said in the news release.

One myeloma expert unconnected to the research was heartened by the findings.

The trial results are "cautiously positive and very encouraging," said hematologist Dr. Kanti Rai. He works in the CLL Research and Treatment Program at Northwell Health Cancer Institute in New Hyde Park, N.Y.

Rai noted that while newer drugs are helping many multiple myeloma patients, others are still left without viable treatment options.

"The need for better treatments is especially urgent for those patients who are elderly, have compromised functions of other vital organs, have had multiple chemotherapy regimens in the past and still have evidence of progressive disease," he explained. "For such patients, unfortunately, death seems imminent."

Rai called the advent of selinexor "a positive step forward for patients with myeloma who otherwise have no hope for the future."

For their part, the Tisch researchers said they are also assessing selinexor for treatment of multiple myeloma in combination with other approved multiple myeloma drugs, as well for treatment of other cancers such lymphoma and ovarian cancer.

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

FDA Approves Turalio (pexidartinib) for the Treatment of Symptomatic Tenosynovial Giant Cell Tumors (TGCT) in Adults

U.S. Food and Drug Administration granted approval to Turalio (pexidartinib) capsules for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not responsive to improvement with surgery.

“TGCT can cause debilitating symptoms for patients such as pain, stiffness and limitation of movement. The tumor can significantly affect a patient’s quality of life and cause severe disability,” said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “Surgery is the primary treatment option, but some patients are not eligible for surgery, and tumors can recur, even after the procedure. Today’s approval is the first FDA-approved therapy to treat this rare disease.”

TGCT is a rare tumor that affects the synovium (thin layer of tissue that covers the surfaces of the joint spaces) and tendon sheaths (layer of membrane that covers tendons, which are fibrous tissue that connect muscle to bone). The tumor is rarely malignant but causes the synovium and tendon sheaths to thicken and overgrow, causing damage to surrounding tissue.

The approval of Turalio was based on the results of a multi-center international clinical trial of 120 patients, 59 of whom received placebo. The primary efficacy endpoint was the overall response rate (ORR) analyzed after 25 weeks of treatment. The clinical trial demonstrated a statistically significant improvement in ORR in patients who received Turalio, with an ORR of 38%, compared to no responses in patients who received placebo. The complete response rate was 15% and the partial response rate was 23%. A total of 22 out of 23 responders who had been followed for a minimum of six months following the initial response maintained their response for six or more months, and a total of 13 out of 13 responders who had been followed for a minimum of 12 months following the initial response maintained their response for 12 or more months.

The prescribing information for Turalio includes a Boxed Warning to advise health care professionals and patients about the risk of serious and potentially fatal liver injury. Health care professionals should monitor liver tests prior to beginning treatment and at specified intervals during treatment. If liver tests become abnormal, Turalio may need to be withheld, the dose reduced, or permanently discontinued, depending on the severity of the liver injury. Turalio is available only through the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program.

Common side effects for patients taking Turalio were increased lactate dehydrogenase (proteins that helps produce energy in the body), increased aspartate aminotransferase (enzymes that are mostly in the liver but also in muscles), loss of hair color, increased alanine aminotransferase (enzymes that are primarily in the liver and kidney) and increased cholesterol. Additional side effects included neutropenia (low level of white blood cells that help the immune system defend against disease and infection), increased alkaline phosphatase (enzymes that are mostly in the cells of bone and the liver), decreased lymphocytes (white blood cells that help the immune system defend against disease and infection), eye edema (swelling around the eyes), decreased hemoglobin (protein in red blood cells that carry oxygen), rash, dysgeusia (altered sense of taste) and decreased phosphate (electrolytes that help with energy).

The FDA advises health care professionals to tell females of reproductive age and males with a female partner of reproductive potential to use effective contraception during treatment with Turalio. Women who are pregnant or breastfeeding should not take Turalio because it may cause harm to a developing fetus or newborn baby. Turalio must be dispensed with a patient Medication Guide that describes important information about the drug’s uses and risks.

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

FDA Approves Xpovio (selinexor) for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

In continuation of my update on Selinexor

Karyopharm Therapeutics Inc. an oncology-focused pharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has approved oral Xpovio (selinexor), a nuclear export inhibitor, in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. The ongoing, randomized Phase 3 BOSTON study evaluating selinexor in combination with Velcade® (bortezomib) and low-dose dexamethasone will serve as the confirmatory trial. The FDA’s Accelerated Approval Program was developed to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need.  

Karyopharm expects Xpovio to become commercially available in the U.S. on or before July 10, 2019.  A Marketing Authorization Application for selinexor is also currently under review by the European Medicines Agency.

“With today’s accelerated approval of Xpovio by the FDA, patients with heavily pretreated multiple myeloma will now have a new therapeutic option to treat their disease,” said Sharon Shacham, PhD, MBA, Founder, President and Chief Scientific Officer of Karyopharm. “Discovering, developing and securing FDA approval for XPOVIO with its novel mechanism of action over the past decade required the dedication of many people, including the patients, caregivers and physicians involved in our clinical trials, along with the many employees at Karyopharm.  We are tremendously grateful for everyone’s contributions to this important milestone, and we look forward to the next stage in our pursuit of improving the lives of patients with cancer.”

“The 25.3% response rate seen in the subgroup of 83 patients in the pivotal Phase 2b STORM study that served as the basis for Xpovio's accelerated approval is clinically meaningful and a validated surrogate marker for clinical benefit in our patients with advanced refractory disease,” said Sundar Jagannath, MD, Director of the Multiple Myeloma Program, Professor of Medicine (Hematology and Medical Oncology) at Tisch Cancer Institute at Mount Sinai School of Medicine, and principal investigator of the STORM study.

“Despite recent advances in the treatment of multiple myeloma, almost all our patients will develop disease that is resistant to the five most commonly used anti-myeloma drugs we currently have available, and the prognosis for this patient population is particularly poor.  The accelerated approval of oral Xpovio marks an important advance in the treatment paradigm for patients with relapsed refractory multiple myeloma, and in my view, is an important addition to our therapeutic armamentarium,” said Dr. Paul Richardson, MD, Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute.

Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm, commented, “Having worked on novel drugs in myeloma beginning with Velcade in the year 2000, I have been thrilled to see such exciting progress overall in the field where there are substantial increases in patients’ duration and quality of life.  The accelerated approval of oral Xpovio targeting XPO1 represents the first approval against a new target in myeloma since 2015, and we look forward to advancing the further clinical development of Xpovio.”

https://pubchem.ncbi.nlm.nih.gov/compound/Selinexor

FDA Approves Thiola EC (tiopronin) for the Treatment of Cystinuria

Retrophin, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved 100 mg and 300 mg tablets of Thiola EC (tiopronin), a new enteric-coated formulation of Thiola (tiopronin), to be used for the treatment of cystinuria, a rare inherited disorder that causes a buildup of cystine levels in the urine resulting in the formation of recurring cystine kidney stones. Thiola EC is expected to be available in July 2019.

“The approval of Thiola EC marks another step in our continued commitment to helping patients with cystinuria manage the threat of recurring cystine stones,” said Eric Dube, Ph.D., chief executive officer of Retrophin. “This new formulation provides patients with the freedom to administer Thiola EC with or without food, an advancement over the original formulation which has limiting food restrictions, and also provides the potential to reduce the number of tablets necessary to manage cystinuria. We look forward to working with the cystinuria community as we make the new formulation available next month.”

The recommended initial dosage of Thiola in adult patients is 800 mg per day and in clinical studies the average dose of Thiola was approximately 1,000 mg, or 10 pills per day. The original formulation of Thiola 100 mg is recommended to be administered at least one hour before or two hours after meals. Thiola EC 100 mg and 300 mg tablets are recommended to be administered with or without food.

“Thiola’s utility as the treatment of choice for cystinuria is well established. However, for certain patients, the challenges of administration one hour before or two hours after meals three times a day, coupled with a high pill burden, have been challenging,” said Dr. David S. Goldfarb, Clinical Chief, Division of Nephrology at NYU Langone Health. “Having a new treatment option with the flexibility of dosing with or without food, as well as one that provides an opportunity for patients to take fewer pills, should meaningfully improve convenience and compliance.”

Thiola EC tablets were approved through the 505(b)(2) regulatory pathway which allows the FDA to reference previous findings of safety and efficacy for an already-approved product, combined with reviewing findings from further studies of the product.

About Thiola EC (tiopronin)

Thiola EC (tiopronin) is indicated, in combination with high fluid intake, alkali, and diet modification for the prevention of cystine stone formation in adults and pediatric patients ≥20 kg with severe homozygous cystinuria, who are not responsive to these measures alone.

https://www.drugbank.ca/drugs/DB06823

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

https://pubchem.ncbi.nlm.nih.gov/compound/5483

Ipsen Announces U.S. FDA Approval for Newly Designed Pre-Filled Syringe for Somatuline Depot (lanreotide)

 

Ipsen Biopharmaceuticals, an affiliate of Ipsen , announced today that the United States Food and Drug Administration (FDA) has approved a new pre-filled syringe for Somatuline Depot (lanreotide). The syringe includes updated features, such as larger flanges, designed to help make it easier for healthcare providers to administer the injection.1 The indications remain the same as those for the previous pre-filled syringe and include the treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival; treatment of adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy; and the long-term treatment of patients with acromegaly who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option. Please see Important Safety Information below and accompanying full Prescribing Information.

“The conditions of GEP-NETs and acromegaly can be associated with a number of uncomfortable and unpleasant symptoms, and innovation aimed at improving the injection process is a step forward,” said Daphne Adelman, Clinical Nurse Specialist, Northwestern University, Chicago, and one of the authors of the study.

Ipsen conducted five separate but complementary studies in partnership with patients, their caregivers, nurses and other healthcare professionals to better understand the current use of the existing Somatuline® Depot pre-filled syringe and to evaluate ways to improve the features of the device.1 The result of this collaboration is a redesigned delivery system intended to make it easy to grip the syringe and administer the injection. The new syringe features a needle shield removal system, more stable plunger and thermoform tray that has recessed areas designed to help prevent accidental plunger depression. The built-in safety system, which may help to prevent needle stick injury by locking in place following the administration, has not been changed.

“We consistently look for opportunities to respond to the needs of the communities we serve, and this approval would not have been possible without the direct involvement of nurses and the patients with GEP-NETs and acromegaly whom they treat,” said Bradley Bailey, SVP, and Franchise Head Oncology/Endocrinology Business Unit at Ipsen. “We listened and collaborated to enhance the existing pre-filled syringe, making it sturdier for healthcare providers when administering treatment, with the intention of improving the injection process. We look forward to bringing this innovation to healthcare providers for their patients soon.”

The new pre-filled syringe is for deep subcutaneous injection and is intended for administration by a healthcare professional. Healthcare providers can expect to receive the new syringe during Q3 2019. The device is approved for use in the U.S., EU and additional ex-U.S. markets.

Dova Pharmaceuticals Announces FDA Approval of Doptelet (avatrombopag) for Treatment of Chronic Immune Thrombocytopenia (ITP)

In continuation of my update on avatrombopag

Dova Pharmaceuticals, Inc.  a pharmaceutical company focused on acquiring, developing and commercializing drug candidates for diseases where there is a high unmet need, today announced the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) that expands the use of Doptelet (avatrombopag) to include the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. 

Doptelet is also FDA-approved for the treatment of thrombocytopenia in adult patients with chronic liver disease (CLD) who are scheduled to undergo a procedure.  Earlier this week, Dova announced the marketing authorization granted by the European Commission for Doptelet for the treatment of severe thrombocytopenia in adult patients with CLD who are scheduled to undergo an invasive procedure.

“Dova is pleased to provide Doptelet to patients and physicians in the United States for the treatment of chronic ITP in adult patients who have had an insufficient response to a previous treatment,” said Dr. David Zaccardelli, president and CEO of Dova. “In addition to offering patients with ITP a new treatment option, we expect Doptelet will also address an important unmet medical need in the market.  We sincerely thank the patients and dedicated researchers who participated in our clinical program as well as FDA for their collaboration during the review of this application.”

Doptelet is an oral, thrombopoietin receptor agonist (TPO-RA) administered with food.  In the pivotal Phase 3 study, Doptelet administration resulted in a platelet count of at least 50,000 per µL at day eight of therapy in the majority of patients, with efficacy superior to placebo in maintaining platelet counts in the target range during the 6-month treatment period.  Additional supportive efficacy data for the ITP sNDA were provided by two Phase 2 ITP clinical trials, as well as two Phase 3 trials for the treatment of thrombocytopenia in patients with CLD. 

Safety data for 128 patients with ITP, and more than 1,000 subjects treated across 24 studies in the Doptelet clinical development program across multiple indications, support the safety and tolerability of Doptelet. 

“ITP patients should work with their clinician to choose a therapy that supports their lifestyle and aims to achieve the best possible result to treat their ITP. That’s why having additional treatment options are so important,” said Caroline Kruse, president and CEO of the Platelet Disorder Support Association, a patient advocacy organization dedicated to ITP patients. “We are thrilled to have a new, oral TPO-RA available for adult patients with ITP.  Every new treatment provides more choices and new hope to our community.”

Dova is committed to enabling patient access to Doptelet.  Doptelet will be priced similarly to other TPO-RAs used to treat ITP, and Dova will continue to offer Patient Assistance and Co-Pay programs. The commercial launch of Doptelet for ITP is anticipated to occur in mid-July 2019. 

Dova also entered into an expanded partnership in the United States with Salix. Starting on July 1, 2019, in addition to the gastroenterology, colorectal surgery, and proctology segments, Salix will have the exclusive right to co-promote the CLD indication for Doptelet to the hepatology and interventional radiology segments.  Dova will continue to pay Salix a commission based on a percentage of net sales in these specialties, which will be in the mid-thirties beginning on July 1, 2019.  In addition, the co-promotion agreement was extended to September 2023.

Dr. Zaccardelli added, “The expanded partnership with Salix builds additional momentum for Doptelet and enables the Dova team to focus on a successful launch of the ITP indication. As a growing leader in the treatment of thrombocytopenia, we are committed to realizing Doptelet’s significant market opportunity in CLD, ITP and potentially chemotherapy-induced thrombocytopenia (CIT) for which we expect Phase 3 trial top-line results in the first half of 2020.”

https://pubchem.ncbi.nlm.nih.gov/compound/AVATROMBOPAG#section=3D-Conformer

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

Experimental Drug, Voxelotor, Shows Early Promise Against Sickle Cell Disease

An experimental drug for sickle cell disease reduced anemia and boosted the health of red blood cells in patients, according to a new study.

Whether the drug, voxelotor, will have long-term health benefits to patients remains to be seen.

But if approved for use by the U.S. Food and Drug Administration, "people living with sickle cell disease might have a new, once daily, tolerable oral medication that increases their hemoglobin level in the near future," noted Dr. Banu Aygun, who wasn't involved in the new trial.

She is associate chief of hematology at Cohen Children's Medical Center in New Hyde Park, N.Y.

As Aygun explained, sickle cell disease is an inherited blood disorder affecting more than 100,000 Americans. Black Americans, especially, are prone to the illness.

"The disease is the result of a change in a single gene leading to the production of an abnormal hemoglobin called sickle hemoglobin [HbS]," Aygun said.

"Due to this abnormal hemoglobin, red blood cells take the shape of a sickle and die much sooner than normal red blood cells. The sickle cells block small blood vessels, causing pain and affecting many organs throughout the body, leading to premature death," she said.

Right now, patients with sickle cell -- many of them children -- have few treatment options. "So far, there are only two FDA-approved drugs for sickle cell disease: hydroxyurea and glutamine," Aygun noted.

The new 17-month, phase 3 clinical trial was designed to see if a third treatment might be on the horizon. It was funded by voxelotor's maker, Global Blood Therapeutics, and included 274 patients, ages 12 to 65, in 12 countries.

Patients were divided into three groups that received either a 900-mg or 1,500-mg daily dose of the drug voxelotor, or a "dummy" placebo pill.

The study found that 51% of patients who took the higher dose of voxelotor had a significant increase in their hemoglobin levels after six months of treatment, compared with 7% of those who received the placebo.

Another finding was that 41% of patients who took the higher dose of the drug reached hemoglobin levels of more than 10g/dl at 24 weeks. A normal, non-anemic hemoglobin count ranges between 11.5 to 17.5 g/dl, depending on age and gender, the study authors noted.

"Chronic organ failure, which is predicted by the severity of anemia, is a leading cause of death for patients with sickle cell disease," said study lead researcher Dr. Elliott Vichinsky, a professor at the University of California, San Francisco.
"These patients are susceptible to strokes, renal failure and other complications that lead to early death," he said in a UCSF news release. "We believe this drug has the potential to decrease chronic organ failure in patients with this condition."

For her part, Aygun said the new drug does seem to hold promise, but gains for patients were so far not dramatic.

She noted that patient pain "events" didn't change, regardless of whether people received voxelotor or the placebo. The most common side effects with the new drug were headache and diarrhea.

And Aygun stressed that it remains to be seen "whether taking this medication for longer duration will lead to a decrease in pain events or organ damage caused by sickle cell disease."

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

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

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