FDA Approves Rybelsus (semaglutide), the First Oral GLP-1 Analog Treatment for Adults with Type 2 Diabetes

In continuation of my updates on Semaglutide

Novo Nordisk today announced that the U.S. Food and Drug Administration (FDA) has approved Rybelsus (semaglutide) tablets 7 mg or 14 mg for adults with type 2 diabetes that along with diet and exercise may improve blood sugar (glucose).  Rybelsus is the first and only glucagon-like peptide-1 (GLP-1) analog in a pill and a new option for adults with type 2 diabetes who are not achieving their A1C goal with current antidiabetic treatment.

Type 2 diabetes is a global public health issue that impacts more than 28 million people in the U.S. alone.2 Despite existing treatment options, many adults with type 2 diabetes have poorly managed blood sugar that can increase the risk of developing serious diabetes-related complications.

"GLP-1 receptor agonists are effective medications for people with type 2 diabetes but have been underutilized in part because they have, until now, only been available as an injectable treatment," said Vanita R. Aroda, MD, Director of Diabetes Clinical Research, Brigham and Women's Hospital, Boston, MA and a PIONEER clinical trial investigator. "The availability of an oral GLP-1 receptor agonist represents a significant development and primary care providers, specialists and patients alike may now be more receptive to the use of a GLP-1 therapy to help them achieve their blood sugar goals."

The approval of Rybelsus is based on results from 10 PIONEER clinical trials, which enrolled 9,543 participants and included head-to-head studies of Rybelsus vs. sitagliptin, empagliflozin and liraglutide 1.8 mg.4 In the trials, Rybelsus reduced A1C and, as a secondary endpoint, showed reductions in body weight. The most common adverse reactions in the PIONEER trials, reported in ≥5% of patients, were nausea, abdominal pain, diarrhea, decreased appetite, vomiting and constipation. The types and frequency of the adverse reactions were similar across trials.

"People living with type 2 diabetes deserve more innovation, research and support to help them achieve their individual A1C goals," said Todd Hobbs, vice president and U.S. chief medical officer of Novo Nordisk. "With Rybelsus, we have the opportunity to expand use of effective GLP-1 receptor agonist therapy by providing adults with type 2 diabetes an oral medication which was previously only available as an injection to help with managing their blood sugar."

Rybelsus is approved for once-daily use in two therapeutic doses, 7 mg and 14 mg, and will be available in the U.S. beginning in Q4 2019. Initial supply of Rybelsus will come from manufacturing facilities in Denmark; however, future supply for Rybelsus will come from manufacturing facilities in the U.S. In 2015, Novo Nordisk made a strategic investment to build a new manufacturing facility in Clayton, NC to prepare for the future demand for Rybelsus. Additionally, earlier this year Novo Nordisk acquired a tableting and packaging facility in Durham, NC to meet anticipated supply needs for Rybelsus.

Novo Nordisk is working with health insurance providers with a goal of ensuring broad insurance coverage and patient access to the product. A savings card program will be available at the time of launch for eligible commercially-insured patients to keep out of pocket costs down to as little as $10 a month.

The U.S. FDA is still reviewing Novo Nordisk's new drug application (NDA) for Rybelsus seeking an additional indication to reduce the risk of major adverse cardiovascular events (MACE) such as heart attack, stroke, or cardiovascular death in adults with type 2 diabetes and established cardiovascular disease (CVD). A decision is expected in Q1 2020.

Rybelsus is currently under review by several regulatory agencies around the world, including the European Medicines Agency and the Japanese Pharmaceuticals and Medical Devices Agency.

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

FDA Approves Ayvakit (avapritinib) for the Treatment of Adults with Unresectable or Metastatic PDGFRA Exon 18 Mutant Gastrointestinal Stromal Tumor

Blueprint Medicines Corporation (NASDAQ: BPMC), a precision therapy company focused on genomically defined cancers, rare diseases and cancer immunotherapy,  announced that the U.S. Food and Drug Administration (FDA) has approved Ayvakit (avapritinib) for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. Ayvakit is the first precision therapy approved to treat a genomically defined population of patients with GIST.

The FDA granted a full approval to Ayvakit based on efficacy results from the Phase 1 NAVIGATOR clinical trial, as well as combined safety results from multiple clinical trials for avapritinib. In patients with PDGFRA exon 18 mutant GIST, Ayvakit had an overall response rate (ORR) of 84 percent (95% CI: 69%, 93%), and a median duration of response (DOR) was not reached. The most common adverse reactions (≥20 percent) were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash and dizziness. Blueprint Medicines plans to make Ayvakit available in the U.S. within a week.

GIST is a rare, genomically driven sarcoma of the gastrointestinal (GI) tract. Approximately 6 percent of patients with newly diagnosed GIST have PDGFRA exon 18 mutations. The most common PDGFRA exon 18 mutation is the D842V mutation, which is resistant to all other approved therapies. A retrospective study showed that when these patients were treated with imatinib, they had an ORR of 0 percent.2

"Today's approval of Ayvakit brings forward a new standard of care for patients with PDGFRA exon 18 mutant GIST, a genomically defined population that previously had very limited treatment options. For the first time, we can offer these patients a highly effective treatment that targets the underlying genetic cause of their disease," said Michael Heinrich, M.D., Professor of Medicine at Oregon Health & Science University and an investigator on the NAVIGATOR trial. "Building on our growing understanding of the molecular basis of GIST, this milestone ushers in a new era of precision medicine in this disease. The FDA approval represents a call to action to conduct mutational testing in all patients with GIST before initiating kinase inhibitor therapy, as recommended by clinical guidelines, so appropriate patients may realize the benefits of this promising new medicine."

"The full approval of Ayvakit based on robust data from our Phase 1 NAVIGATOR clinical trial is an incredibly exciting milestone for our company and, more importantly, for GIST patients with a PDGFRA exon 18 mutation, who have been waiting for a new treatment option," said Jeff Albers, Chief Executive Officer at Blueprint Medicines. "Ayvakit is the first of what we hope will be many approved medicines enabled by our research platform. Now, as we begin to deliver Ayvakit to patients and their healthcare providers, we aim to fortify our leadership in the field of precision medicine and build a foundation for our broader portfolio by pairing our strong research and development capabilities with an equally talented commercial organization focused on addressing patient needs, accelerating diagnostic testing and enabling access."

Blueprint Medicines is dedicated to helping patients with PDGFRA exon 18 mutant GIST access treatment with Ayvakit and providing robust support throughout their treatment journey. As part of this commitment, Blueprint Medicines is introducing YourBlueprint™, a patient support program that offers access and affordability solutions for individuals receiving Ayvakit. For more information, visit YourBlueprint.com or call 1-888-BLUPRNT (1-888-258-7768), Monday to Friday, 8:00 a.m. to 8:00 p.m. ET. Healthcare providers who prescribe Ayvakit can fill out an enrollment form at YourBlueprint.com/HCP to help patients access Blueprint Medicines' support services.

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

FDA Approves Ibsrela (tenapanor) for the Treatment of Irritable Bowel Syndrome with Constipation

Ardelyx, Inc. announced that the U.S. Food and Drug Administration has approved Ibsrela (tenapanor), a 50 mg, twice daily oral pill for the treatment of irritable bowel syndrome with constipation (IBS-C) in adults. Ibsrela is a minimally-absorbed small molecule that acts locally in the gastrointestinal (GI) tract to inhibit the sodium-hydrogen exchanger NHE3, resulting in an increase in bowel movements and a decrease in abdominal pain for IBS-C patients.

"Ibsrela has the potential to provide IBS-C patients and their doctors with a novel mechanism and an innovative approach to managing IBS-C, a highly burdensome and difficult-to-treat condition affecting more than 11 million people in the United States," commented Mike Raab, president and chief executive officer of Ardelyx.  "This approval is an extremely important and rewarding milestone for Ardelyx, and represents the culmination of years of dedication to advancing our discoveries and medicines in an effective and rigorous manner. We look forward to establishing a commercial collaboration with a partner that has the capabilities to drive the successful launch and marketing of Ibsrela in this large and underserved IBS-C patient population."

Mr. Raab continued, "With the approval of Ibsrela for IBS-C, along with the successful completion of our AMPLIFY trial in hyperphosphatemia, we've delivered on two major corporate milestones in the last two weeks due to flawless execution by the remarkable and talented team at Ardelyx. With these milestones accomplished, and the PHREEDOM trial reading out in Q4, I have great confidence that we are well positioned to file our NDA for hyperphosphatemia next year with potential approval and launch in 2021. We are excited about this next chapter for Ardelyx as we begin the development of our playbook for launch and commercialization of tenapanor for hyperphosphatemia in chronic kidney disease patients on dialysis and are excited to begin sharing more of our vision in the coming months." 

Ibsrela (tenapanor) Phase 3 IBS-C Program 

Phase 3 Study Designs

The Phase 3 IBS-C program included two randomized, double-blind, placebo-controlled trials. The trial designs were identical through the first 12 weeks of treatment, and thereafter differed in that Trial 1 (NCT02686138) continued for an additional 14 weeks of treatment (26 weeks double-blind treatment), whereas Trial 2 (NCT02621892) included a 4-week randomized withdrawal (RW) period (12 weeks double-blind treatment). Patients who were enrolled in these trials met the Rome III criteria for IBS-C, related to abdominal pain and bowel movement frequency. 

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

FDA Approves Vumerity (diroximel fumarate) for Multiple Sclerosis

 Biogen Inc. (Nasdaq: BIIB) and Alkermes plc (Nasdaq: ALKS),  announced  the U.S. Food and Drug Administration (FDA) approval of Vumerity (diroximel fumarate), a novel oral fumarate with a distinct chemical structure, for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease and active secondary progressive disease. Biogen holds the exclusive, worldwide license to commercialize Vumerity and intends to make it available in the United States in the near future.

“The FDA’s approval of Vumerity delivers on Biogen’s commitment to pursue new therapies that may provide meaningful impact for people living with relapsing MS, and we look forward to bringing it to the MS community as an additional treatment option,” said Alfred Sandrock, Jr., M.D., Ph.D., executive vice president, research and development, and chief medical officer at Biogen. “Vumerity is a novel fumarate that offers the well-characterized efficacy of Tecfidera® (dimethyl fumarate) and has been studied for improved patient-reported gastrointestinal tolerability.”

“The approval of Vumerity for relapsing MS marks the culmination of a multi-year development program and is the latest milestone in our mission to develop new treatments for patients living with chronic central nervous system disorders,” said Craig Hopkinson, M.D., chief medical officer and senior vice president of medicines development and medical affairs at Alkermes. “We are grateful to the patients and study investigators who have participated in our Vumerity clinical trials and we look forward to working with our collaboration partners at Biogen to make this new treatment available to patients.”

The FDA approval of Vumerity was based on a New Drug Application (NDA) submitted under the 505(b)(2) filing pathway. It included data from pharmacokinetic bridging studies comparing Vumerity and Tecfidera to establish bioequivalence, and relied, in part, on the FDA’s findings of safety and efficacy for Tecfidera.

The NDA submission also included interim exposure and safety findings from EVOLVE-MS-1, an ongoing, Phase 3, single-arm, open-label, two-year safety study evaluating Vumerity in patients with relapsing-remitting MS. Interim results from EVOLVE-MS-1 at the time of NDA submission included a low overall rate of Vumerity treatment discontinuation due to adverse events (6.3 percent), and a rate of less than one percent of patients who discontinued Vumerity treatment due to gastrointestinal (GI) adverse events. Additional exploratory efficacy endpoints in the ongoing EVOLVE-MS-1 study showed changes in clinical and radiological measures compared to baseline.

“MS is a heterogeneous disease, and real-world patient circumstances can vary, reinforcing the benefits of having therapeutic choices to support the diverse range of treatment considerations,” said Robert Naismith, M.D., professor of neurology, Washington University School of Medicine in St. Louis. “Throughout its clinical development program, Vumerity has demonstrated a desirable therapeutic profile, making it a compelling new option for patients.”

“MS is a lifelong disease that has a significant impact on the people affected and their caregivers. We are encouraged by the progress being made in the treatment of MS, and pleased that another treatment option will soon be available,” said Bruce Bebo, Ph.D., executive vice president, research, National MS Society. “It’s important for people with MS to have treatments that are both efficacious and tolerable to help manage their disease.”

Under the terms of the license and collaboration agreement between Biogen and Alkermes, Biogen will pay Alkermes $150 million in connection with the FDA’s approval of Vumerity. Biogen plans to account for this milestone payment as an asset that will be amortized over the expected useful life of the product. Alkermes is also entitled to receive a mid-teens percentage royalty on worldwide net commercial sales of Vumerity, subject, under certain circumstances, to minimum annual payments for the first five years following FDA approval and customary reductions as set forth in the agreement.

https://www.drugbank.ca/drugs/DB14783

FDA Approves Biorphen (phenylephrine hydrochloride) Ready-to-Use Injection for Hypotension During Anesthesia

In continuation of my update on phenylephrine

Eton Pharmaceuticals, Inc. (Nasdaq: ETON), a specialty pharmaceutical company focused on developing and commercializing innovative drug products, today announced that the U.S. Food and Drug Administration (FDA) has approved Biorphen, the first and only FDA-approved ready-to-use formulation of phenylephrine for the treatment of clinically important hypotension resulting primarily from vasodilation in the setting of anesthesia.

Prior to the FDA approval of Biorphen, phenylephrine injection was only approved and available as a highly concentrated formulation that required hospitals to manually dilute the concentrate prior to administration, or purchase ready-to-use formulations from 503B compounding pharmacies. Compounded drugs do not have to undergo FDA premarket review for safety, effectiveness and certain controls over manufacturing quality. Due to this lower regulatory standard, compounded drugs are often associated with higher risks of medication error.

“Today’s FDA approval of Biorphen addresses a critical medical need for an approved, ready-to-use standardized formulation of phenylephrine that can potentially reduce medication administration errors and improve patient safety,” said Sean Brynjelsen, chief executive officer of Eton Pharmaceuticals. "The approval of Biorphen represents an important step forward in Eton’s commitment to improving existing medicines to address unmet patient needs. We look forward to working with our manufacturing partner, Sintetica, to make Biorphen available to hospitals across the United States before the end of the year.” 

“Operating rooms, emergency departments and intensive care units are fast-paced and time-sensitive environments. Add to that the complexity of caring for patients with a wide range of critical conditions and the use of high-alert medications like phenylephrine – and you have an atmosphere primed for potential medication error,” said Jared Marcucci, M.D., assistant director, Community First Medical Center Department of Emergency Medicine in Chicago. “As a practicing emergency medicine physician, the availability of an FDA-approved, ready-to-use formulation of phenylephrine is a welcome advance, providing physicians and hospital systems with an important new option that does not require compounding and can potentially help reduce the risk of medication errors and minimize harm to patients.”

“Providers at the bedside need reliable, easy to use, safe drugs that have a consistent supply.  Many hospitals outsource unapproved ready-to-use phenylephrine from 503B compounders, however often have to navigate supply disruptions through these suppliers,” said Heather Nixon, M.D., Associate Professor Anesthesiology, University of Illinois at Chicago Hospital. “The availability of Biorphen will help address many of the underlying causes for risk and error associated with compounded phenylephrine while also reducing potential for waste associated with overdrawing medications. This will be an important new tool for anesthesiologists, pharmacists and other hospital providers in their efforts to enhance patient safety and prevent patient harm.” 

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

FDA Approves Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for Cystic Fibrosis Patients Ages 12 and Older Who Have at Least One F508del Mutation

In continuation of my update on  tezacaftor  and ivacaftor

Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the U.S. Food and Drug Administration (FDA) has approved Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for the treatment of cystic fibrosis (CF) in people ages 12 years and older who have at least one F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the most common CF-causing mutation. With this approval, for the first time, approximately 6,000 people with CF ages 12 years and older who have one F508del mutation and one minimal function mutation (F/MF) have a medicine that targets the underlying cause of their CF. Additionally, approximately 12,000 people with one or two F508del mutations who are currently eligible for one of Vertex’s three other FDA-approved CF medicines are now also eligible for Trikafta.

“Today marks a milestone for CF patients, their families and Vertex. After a 20-year journey together, we have received FDA approval of Trikafta: a single breakthrough medicine with the potential to treat up to 90% of all people with CF in the future. For approximately 6,000 people with CF in the U.S., Trikafta is the first medicine that can treat the underlying cause of their disease,” said Jeffrey Leiden, M.D., Ph.D., Vertex's Chairman, President and Chief Executive Officer. “I want to personally thank the hundreds of Vertex scientists who have been working on this program for nearly 20 years – many of whom have dedicated their entire careers to changing the course of this disease; the CF Foundation which has provided support, encouragement and help throughout the journey; and most importantly the thousands of patients, caregivers, doctors and advocates who have courageously and persistently worked side-by-side with us to get to where we are today.”

“Today’s approval is a historic moment in cystic fibrosis care, with the potential for more people to benefit from CFTR modulator therapy to treat the basic defect of their disease,” said Steven Rowe, M.D., Director, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham. “In clinical trials, Trikafta was generally well tolerated and demonstrated improvements in multiple outcome measures in CF, including improvements in FEV1, improvements in respiratory symptoms and, in the 24-week F/MF study, a reduced rate of pulmonary exacerbations and improvements in BMI.”

“The incredible speed of this approval underscores our shared sense of urgency with the FDA and the CF community for bringing this medicine to eligible people with CF, particularly those without a medicine targeting the underlying cause of their disease,” said Reshma Kewalramani, M.D., Executive Vice President, Global Medicines Development and Medical Affairs and Chief Medical Officer at Vertex. “We remain committed to relentlessly pursuing the development of transformative therapies for all people living with this disease.”

Vertex has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for the elexacaftor/tezacaftor/ivacaftor combination regimen. Vertex is currently evaluating elexacaftor/tezacaftor/ivacaftor in people ages 6 through 11 with F/MF and F/F CF mutations in an ongoing Phase 3 study and is committed to evaluating elexacaftor/tezacaftor/ivacaftor in children <6 years of age as part of planned future studies.

     

https://en.wikipedia.org/wiki/Elexacaftor/ivacaftor/tezacaftor

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

https://en.wikipedia.org/wiki/Elexacaftor/ivacaftor/tezacaftor

FDA Approves Trikafta (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for Cystic Fibrosis Patients Ages 12 and Older Who Have at Least One F508del Mutation

FDA Approves Amzeeq (minocycline) Topical Foam for the Treatment of Moderate to Severe Acne

Foamix Pharmaceuticals Ltd. (Nasdaq: FOMX) (“Foamix” or the “Company”), a specialty pharmaceutical company, announced  the U.S. Food and Drug Administration (FDA)   approval of its novel Amzeeq (minocycline) topical foam, 4%. Amzeeq, formerly known as FMX101, is indicated for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and pediatric patients 9 years of age and older and is the first topical minocycline to be approved by the FDA for any condition.

“The FDA approval of Amzeeq is a milestone moment in dermatology and the most significant advancement with minocycline in almost 50 years,” said David Domzalski, Chief Executive Officer of Foamix. “We are proud that our proprietary technology platform has led to this new treatment option, which we believe can help address unmet treatment needs for moderate to severe acne patients. We are looking forward to bringing Amzeeq to market in January 2020, and to our Company’s first commercial launch.”

Minocycline is a broad-spectrum antibiotic known for its efficacy in treating moderate to severe acne, but its use is limited in some patients due to systemic side effects when taken orally. Until now, minocycline has not been available as a topical treatment due to its instability in traditional topical formulations. In Amzeeq, Foamix has leveraged its proprietary Molecule Stabilizing Technology (MST™) platform to effectively deliver minocycline in a foam-based vehicle.  

“Our innovative MST™ technology allowed us to develop a topical formulation of minocycline in a convenient, once-daily treatment regimen that maintains the stability of the active ingredient while delivering it into the skin,” said Iain Stuart, Ph.D, Chief Scientific Officer of Foamix. “The approval of Amzeeq represents a significant step toward our goal of enhancing the standard of care for the millions of acne sufferers in the U.S. who deserve alternatives in treatment.”

“The approval of Amzeeq is exciting news that provides a much-needed option in the treatment of moderate to severe acne,” said Linda Stein Gold, M.D., Director of Dermatology Clinical Research and Division Head of Dermatology at Henry Ford Health System in Detroit, Michigan. “Minocycline has been a trusted staple in acne treatment for decades, but has only been available in oral or systemic formulations. With the approval of Amzeeq, I can now offer my patients a new, effective topical treatment option with a favorable tolerability profile.”

The FDA approval of Amzeeq is supported by data from three Phase 3 clinical trials in 2,418 patients of 9 years of age or older, making it one of the largest clinical programs for acne to date. In each 12-week, multicenter, randomized, double-blind, vehicle-controlled study, subjects with moderate to severe acne vulgaris were treated once-daily with Amzeeq or vehicle. No other topical or systemic acne medication was permitted to be used by subjects during the study period. The studies each found statistically significant disease improvement with Amzeeq versus vehicle for the co-primary endpoint of absolute reduction of inflammatory lesions, while studies 2 and 3 demonstrated a statistically significant improvement in IGA treatment success. IGA treatment success was defined as a score of 0 (“clear”) or 1 (“almost clear”) and at least a two-point decrease from baseline. Amzeeq was well-tolerated and no treatment-related serious adverse events were reported. The most common adverse reaction was headache, which was reported in 3% of subjects treated with Amzeeq versus 2% of subjects treated with vehicle.

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

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

In continuation of my update on Asenapine

Noven Pharmaceuticals, Inc., a wholly-owned subsidiary of Hisamitsu Pharmaceutical Co., Inc., has announced the U.S. Food and Drug Administration (FDA) has approval of  Secuado (asenapine) 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.

“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. The most commonly observed adverse reactions were extrapyramidal disorder, application site reaction, and weight gain. 

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

FDA Approves Reyvow (lasmiditan), the First Serotonin (5-HT) 1F Receptor Agonist for the Acute Treatment for Migraine

Eli Lilly and Company (NYSE: LLY) announced today that the U.S. Food and Drug Administration (FDA) has approved Reyvow (lasmiditan) an oral medication for the acute treatment of migraine, with or without aura, in adults. Reyvow has a unique mechanism of action and is the first and only FDA-approved medicine in a new class of acute treatment for migraine (serotonin (5-HT)1F receptor agonists).

"Millions of people with migraine face an ongoing battle with the unresolved pain and symptoms of a migraine attack. There is a substantial unmet need for new acute treatments for migraine, like Reyvow, which is why we are proud of today's approval and Lilly's continuing contribution to the migraine community," said Gudarz Davar, M.D., vice president, neurology development, Lilly Bio-Medicines. "New expectations have been set in migraine care; pain freedom is now the treatment goal for people living with migraine and those who treat them. At Lilly, we are pioneering innovative medicines to provide new options for patients with migraine."

As with other medicines with central nervous system (CNS) activity, the FDA required abuse potential studies for Reyvow. Abuse potential refers to the likelihood that abuse will occur with a particular drug product or substance with CNS activity. Consistent with the FDA's guidance, Lilly conducted a human abuse potential assessment; as part of that assessment, therapeutic doses of Reyvow were associated with less drug liking when compared to alprazolam, but more than placebo. The recommended controlled substance classification for Reyvow is currently under review by the Drug Enforcement Administration (DEA) and is expected within 90 days of today's FDA approval, after which Reyvow will be available to patients in retail pharmacies.

"As a physician who specializes in the treatment of migraine and headache disorders, I commonly treat patients who are looking for acute treatment options that offer the chance for pain freedom during migraine attacks. This approval is especially significant because migraine pain is so often severe and incapacitating," said Jan Brandes, M.D., MS, FAAN, assistant clinical professor, Department of Neurology, Vanderbilt University. "With new science comes new hope. Considering up to 40% of people with migraine do not get adequate responses from their initial acute treatment prescription, having a new and novel option like Reyvow is an important development for physicians and the patients we treat.

The New Drug Application (NDA) for Reyvow included data from two Phase 3 single-attack studies (SAMURAI and SPARTAN), which evaluated the safety and efficacy of Reyvow for the acute treatment of migraine in adults. Both studies met the efficacy endpoints of pain freedom and freedom from most bothersome symptom (MBS; patient selected from nausea, sensitivity to light, or sensitivity to sound) at two hours following administration of Reyvow in comparison to placebo. Treatment emergent adverse events were generally mild to moderate and the most frequent included dizziness, fatigue, paresthesia (tingling or numbing sensation on the skin), sedation (sleepiness or drowsiness), nausea and/or vomiting and muscle weakness. See additional Important Safety Information below.

The Reyvow Phase 3 development program, including the open-label GLADIATOR study, involved more than 4,000 patients and the treatment of more than 20,000 migraine attacks.

"For over 25 years, Lilly has been committed to helping people affected by disabling headache disorders, investigating more than a dozen different compounds," said Patrik Jonsson, senior vice president and president, Lilly Bio-Medicines. "The approval of Reyvow is an exciting development for patients and physicians seeking the potential for pain freedom when a migraine attack happens."

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

FDA Approves Quzyttir (cetirizine) Injection for the Treatment of Acute Urticaria

The U.S. Food and Drug Administration (FDA) has approved Quzyttir (cetirizine hydrochloride) injection for the treatment of acute urticaria in adults and children 6 months of age and older. Quzyttir will be available as 10-mg/mL single-use vials for intravenous use.

The safety and efficacy of Quzyttir was demonstrated in a randomized, active-controlled, double-blind, single dose, multicenter, parallel group trial of 262 patients aged 18 years of age and older who presented to an emergency department or urgent care center with acute urticaria. Patients were treated with either 10 mg of Quzyttir, or 50 mg diphenhydramine injection. The primary efficacy endpoint was the change from baseline in patient-rated pruritus score assessed 2 hrs post treatment. 

Quzyttir injection was demonstrated to be non-inferior to the effectiveness of diphenhydramine injection. Additionally, the proportion of patients returning to any emergency department or clinic was lower in the Quzyttir treatment group (6%) compared to the diphenhydramine treatment group (14%), and the time spent in the treatment center was shorter.

The adverse reactions with Quzyttir occurred at an incidence of less than 1% and include: dyspepsia, feeling hot, dysgeusia, headache, paresthesia, presyncope, and hyperhidrosis.

Quzyttir is the first intravenous (IV) formulation of the histamine-1 (H1) receptor antagonist cetirizine. The first oral formulation of cetirizine was approved under the brand name Zyrtec in 1995

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

FDA Approves Scenesse (afamelanotide) for Prevention of Phototoxicity in Erythropoietic Protoporphyria

The U.S. Food and Drug Administration  has  granted approval to Scenesse (afamelanotide) to increase pain-free light exposure in adult patients with a history of phototoxic reactions (damage to skin) from erythropoietic protoporphyria.

For patients who are suffering from erythropoietic protoporphyria, a rare disorder, exposure to light may be extremely painful. Prior to today’s approval, there were no FDA-approved treatments to help erythropoietic protoporphyria patients increase their light exposure,” said Julie Beitz, M.D., director of FDA’s Center for Drug Evaluation and Research Office of Drug Evaluation III. “Today’s approval is one example of the FDA’s ongoing commitment to encourage industry innovation of therapies to treat rare diseases, and work with drug developers to make promising new therapies available to patients as safely and efficiently as possible.”

Erythropoietic protoporphyria is a rare disorder caused by mutations leading to impaired activity of ferrochelatase, an enzyme involved in heme production. Heme is an important component in hemoglobin, the oxygen carrying molecule in red blood cells. The decrease in ferrochelatase activity leads to an accumulation of protoporphyrin IX (PPIX) in the body. Light reaching the skin can react with PPIX causing intense skin pain and skin changes, such as redness and thickening. Scenesse (afamelanotide), a melanocortin-1 receptor (MC1-R) agonist, increases the production of eumelanin in the skin independent of exposure to sunlight or artificial light sources.  It is an implant that is administered subcutaneously (inserted under the skin). 

The efficacy of Scenesse was established in two parallel group clinical trials with patients with erythropoietic protoporphyria who received Scenesse or placebo form of the implant subcutaneously every two months. The first clinical trial enrolled 93 subjects, of whom 48 received Scenesse, and were followed for 180 days. The primary endpoint was the total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. on days with no pain. The median total number of hours over 180 days spent in direct sunlight between 10 a.m. and 6 p.m. on days with no pain was 64 hours for patients receiving Scenesse and 41 hours for patients taking placebo.

The second clinical trial enrolled 74 patients, of whom 38 received Scenesse, and were followed for 270 days. The primary endpoint was the total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight. The analysis did not include sun exposure on days patients reported spending time in a combination of both direct sunlight and shade. The median total number of hours over 270 days spent outdoors between 10 am and 3 pm on days with no pain for which “most of the day” was spent in direct sunlight was six hours for patients receiving Scenesse and 0.75 hours for patients receiving placebo. 

Scenesse’s most common side effects are implant site reaction, nausea, oropharyngeal (part of the throat just behind the mouth, where the oral cavity starts) pain, cough, fatigue, skin hyperpigmentation, dizziness, melanocytic nevus (moles), respiratory tract infection, somnolence (feeling drowsy), non-acute porphyria (build-up of normally occurring molecules created during heme production) and skin irritation. Scenesse should be administered by a health care professional who is proficient in the subcutaneous implantation procedure and has completed the applicant-provided training. Scenesse may induce skin darkening, and a full body skin examination is recommended for patients twice a year. In addition, patients are encouraged to maintain sun protection measures during treatment with Scenesse to prevent phototoxic reactions related to erythropoietic protoporphyria.

The FDA granted this application Priority Review designation. Scenesse also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.The approval of Scenesse was granted to Clinuvel.

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

FDA Approves Bonsity (teriparatide injection) to Treat Osteoporosis

In continuation of my update on teriparatide

Pfenex Inc. (NYSE American: PFNX) announced today that the U.S. Food and Drug Administration (FDA) has approved the new drug application (“NDA”) for Bonsity (PF708) submitted under the 505(b)(2) regulatory pathway, with Forteo® (teriparatide injection) as the reference drug. Like Forteo, the FDA-approved PF708 product is indicated for the treatment of osteoporosis in certain patients at high risk for fracture. 

“The FDA’s approval of Bonsity marks a major milestone in Pfenex’s history as our first approved commercial product and further validates our Pfēnex Expression Technology platform. We look forward to continuing to work with our commercialization partner Alvogen to launch PF708 in the U.S. We believe PF708 has the potential to significantly enhance patient access to an important therapy as a cost-effective alternative to Forteo, which had $1.6 billion in global sales in 2018,” said Eef Schimmelpennink, Chief Executive Officer of Pfenex.

Pfenex is also asking the FDA to designate PF708 as therapeutically equivalent (“A” rated) to Forteo, which would permit PF708 to be automatically substituted for Forteo in many states. To further support an “A” rating, Pfenex is conducting a comparative human factors study between PF708 and Forteo as requested by FDA. Pfenex anticipates submitting the final study report to the FDA as early as the second half of October 2019 and believes that this completes the information package required by the FDA to evaluate the therapeutic equivalence of PF708.

“Looking ahead, we are confident in the planning that Alvogen has done thus far in preparation for the commercial launch of PF708 and their established sales and marketing teams are excited to bring PF708 to market. To optimize patient and payer impact, we currently expect our commercial partner Alvogen to launch PF708 upon an FDA decision on the therapeutic equivalence rating,” concluded Mr. Schimmelpennink.

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

FDA Approves Aklief (trifarotene) Cream, a New Topical Retinoid for the Treatment of Acne

Galderma, a global leader focused on meeting the world's increasing skin health needs, announced today that the U.S. Food and Drug Administration (FDA) approved Aklief (trifarotene) Cream, 0.005% for the topical treatment of acne. Aklief Cream is the only topical retinoid that selectively targets retinoic acid receptor (RAR) gamma, the most common RAR found in the skin.1,2,3 Trifarotene is the first new retinoid molecule to receive U.S. FDA approval for the treatment of acne in more than 20 years.4,5,6 Aklief Cream is the first topical treatment specifically studied and proven to treat both facial (forehead, cheeks, nose and chin) and truncal (chest, shoulders and back) acne, offering healthcare professionals and acne patients another treatment option.

"While retinoids are foundational therapies to treat acne, there has been little innovation in decades.” said Sandra Johnson, M.D., FAAD, an investigator in the clinical trials of Aklief Cream and a dermatologist at Johnson Dermatology in Fort Smith, Arkansas. “With the approval of Aklief Cream, I am excited to offer my patients a unique, highly targeted retinoid that reduces inflammatory lesions on the face, back, chest and shoulders, that has also been shown to be safe and well-tolerated."

The FDA approval of Aklief Cream is supported by data from the two pivotal Phase 3 clinical trials of once-daily Aklief Cream in patients with moderate acne on the face and trunk.1 The two identical 12-week, randomized, multicenter, parallel group, double-blind, vehicle-controlled clinical trials of 2,420 patients showed that Aklief Cream significantly reduced inflammatory lesions as early as two weeks on the face and four weeks on the back, shoulders and chest compared to vehicle (p<0.05).1 Aklief Cream was well tolerated when used on the face, back, shoulders and chest.1 The most common adverse reactions (incidence >1%) included application site irritation, application site pruritus (itching) and sunburn.1 

“The approval of Aklief Cream underscores our ability to bring new active molecules to the community, and innovate even in well-established therapeutic classes. It is consistent with our intent to change the paradigm of how even the most common and frustrating skin diseases are treated, including acne,” said Thibaud Portal PhD, Galderma Global Vice President, Prescription. “We are pleased to add this new treatment option, with proven efficacy in facial and truncal acne, to our innovative and differentiated portfolio of acne treatments.”

Aklief Cream is expected to be available in the United States in November 2019. It will be provided in a 45 gram pump. Galderma is working closely with payers, providers and pharmacy benefit managers to ensure broad and rapid access to Aklief Cream. The company will also offer a patient savings card program, Galderma CareConnect*.

*Galderma CareConnect is only available for commercially insured or uninsured patients. Patients who are enrolled in a government-run or government-sponsored healthcare plan with a pharmacy benefit are not eligible to use the Galderma CareConnect Patient Savings Card.

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