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

FDA Approves Xcopri (cenobamate) for the Treatment of Partial-Onset Seizures in Adults

 

In continuation of my update on cenobamate

SK Biopharmaceuticals, Co., Ltd., an innovative global pharmaceutical company focused on developing and bringing treatments to market for central nervous system (CNS) disorders, and its U.S. subsidiary SK Life Science, Inc. announced today that the U.S. Food and Drug Administration (FDA) approved Xcopri (cenobamate tablets) as a treatment for partial-onset seizures in adults.

"The approval of Xcopri will provide clinicians with an effective medication for our patients who are continuing to have focal (partial-onset) seizures," said Michael Sperling, MD, Professor of Neurology and Director of the Jefferson Comprehensive Epilepsy Center at the Vickie and Jack Farber Institute for Neuroscience – Jefferson Health in Philadelphia, and an investigator in the Xcopri clinical development program. "It is very encouraging to see that patients receiving Xcopri saw significant reductions in frequency of seizures, with some even achieving zero seizures." 

The approval is based on results from two global, randomized, double-blind, placebo-controlled studies and a large, global, multi-center, open-label safety study that enrolled adults with uncontrolled partial-onset seizures, taking one to three concomitant anti-epileptic drug (AEDs). In the randomized studies (Study 013 and Study 017), Xcopri demonstrated significant reductions in seizure frequency compared to placebo at all doses studied.

"Approximately 3 million adults live with epilepsy in the U.S. and according to the Centers for Disease Control and Prevention (CDC), nearly 60% reported having seizures, even if they took an AED," said Beth Lewin Dean, Chief Executive Officer of Citizens United for Research in Epilepsy (CURE). "There is an urgent need to advance research and introduce new treatment options. The FDA approval of Xcopri for the treatment of partial-onset seizures is a welcome option for the epilepsy community."

The approval also marks the first time a Korean company has independently brought a compound from discovery to U.S. FDA approval.

"Today's approval is a major step toward our goal of becoming a fully-integrated global pharmaceutical company that can discover, develop and deliver new treatment options in epilepsy and CNS," said Jeong Woo Cho, PhD, President and CEO of SK Biopharmaceuticals and SK life science. "We are grateful to the thousands of participants in our trials, clinical investigators, partners in the epilepsy community and our employees for their important contributions in bringing forward this treatment option for adults with partial-onset seizures."

In Study 013, which included a 6-week titration phase followed by a 6-week maintenance phase, a statistically significant 56% reduction in median seizure frequency was seen with Xcopri 200 mg/day (n=113) versus a 22% reduction with placebo (n=108). In Study 017, which included a 6-week titration phase followed by a 12-week maintenance phase, patients randomized to Xcopri 100 mg/day (n=108), 200 mg/day (n=109) or 400 mg/day (n=111) had statistically significant 36%, 55% and 55% reductions in median seizure frequency, respectively, versus a 24% reduction with placebo (n=106). During the maintenance phase of Study 013, a post-hoc analysis showed that 28% of patients receiving Xcopri had zero seizures, compared with 9% of placebo patients. During the maintenance phase of Study 017, 4% of patients in the Xcopri 100 mg/day group, 11% of patients in the Xcopri 200 mg/day group, 21% of patients in the Xcopri 400 mg/day group and 1% of patients in the placebo group reported zero seizures.

Serious reactions associated with Xcopri include drug reaction with eosinophilia and systemic symptoms (DRESS), QT shortening, suicidal behavior and ideation, and neurological adverse reactions. The most common (≥10% and greater than with placebo) treatment-emergent adverse events associated with Xcopri include somnolence (sleepiness), dizziness, fatigue, diplopia (double vision) and headache.

Xcopri is expected to be available in the U.S. in the second quarter of 2020, following scheduling review by the DEA, which typically occurs within 90 days of FDA approval. SK life science is committed to supporting patients taking Xcopri and will introduce a new access program to help patients get started and stay on track with their medicine.

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

FDA Approves Givlaari (givosiran) for Acute Hepatic Porphyria

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the U.S. Food and Drug Administration (FDA) approved Givlaari (givosiran) injection for subcutaneous use for the treatment of adults with acute hepatic porphyria (AHP). AHP is a family of ultra-rare, genetic diseases characterized by debilitating, potentially life-threatening attacks and, for some patients, chronic manifestations that negatively impact daily functioning and quality of life. Long-term complications of AHP can include chronic neuropathic pain, hypertension, chronic kidney disease and liver disease. Givlaari was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or IV hemin administration at home.

“We believe the approval of Givlaari represents a landmark event for the advancement of precision genetic medicines, providing new hope for patients and their caregivers living with the debilitating manifestations of AHP and unpredictable nature of AHP attacks, as well as for the doctors who diagnose and treat these patients. We are grateful to the investigators, patients and families who have helped make this new treatment option a reality for the AHP community. We also commend the FDA for recognizing the immense medical need and granting this approval so quickly,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “Givlaari now becomes our second RNAi therapeutic to be approved in the last 16 months, and the world’s first-ever GalNAc-conjugate RNA therapeutic to be approved, representing a watershed moment for a technology uniquely pioneered by Alnylam scientists. We believe today’s news reinforces the promise and potential of RNAi therapeutics as a whole new class of medicines and brings us one important step closer to fulfilling our Alnylam 2020 goals of building a multi-product, global commercial company with a deep clinical pipeline to drive growth and an organic product engine to fuel sustainable innovation.”

The FDA approval of Givlaari was received in less than four months after acceptance of the NDA, and was based on positive results from the ENVISION Phase 3 study, a randomized, double-blind, placebo-controlled, multinational study of 94 patients with AHP, at 36 study sites in 18 countries – the largest ever interventional study conducted in AHP. In ENVISION, AHP patients on Givlaari experienced 70% (95% CI: 60%, 80%) fewer porphyria attacks compared to placebo. Givlaari also resulted in a similar reduction in intravenous hemin use, as well as reductions in urinary aminolevulinic acid (ALA), and urinary porphobilinogen (PBG).

In the pivotal ENVISION study, the most common adverse reactions (reported in at least 20% of patients) with Givlaari were nausea (27%) and injection site reactions (25%). Other adverse reactions seen in patients treated with Givlaari (occurring over 5% more frequently than placebo) include rash, serum creatinine increase, transaminase elevations and fatigue. As previously reported, one patient in the Givlaari clinical development program experienced an anaphylactic reaction which resolved with medical management.

“Adults with AHP now have a new treatment option that has demonstrated the ability to reduce the frequency of porphyria attacks by specifically addressing factors associated with attacks and other disease manifestations of AHP,” said Manisha Balwanii, M.D., M.S, Associate Professor of the Department of Genetics and Genomic Sciences and Department of Medicine at the Icahn School of Medicine at Mount Sinai and principal investigator of the ENVISION study. “With the approval of Givlaari, and based on the efficacy data from the ENVISION study, I hope to see my patients and those across the country be able to live more normal lives with fewer porphyria attacks.”

“The FDA approval of Givlaari is an important milestone for our community, as we now have a new treatment option for adults living with acute hepatic porphyria,” said Kristen Wheeden, Executive Director, American Porphyria Foundation. “AHP can have a profound impact on the lives of patients and their families. Porphyria attacks are associated with severe, incapacitating pain, often requiring hospitalization for management. In addition, many patients struggle on a daily basis with chronic symptoms related to their disease. The approval of Givlaari is exciting for our community.”

Alnylam is committed to helping people access the medicines they are prescribed and will be offering comprehensive support services for people prescribed Givlaari through Alnylam Assist®. Visit AlnylamAssist.com for more information or call 1-833-256-2748.

Givlaari is expected to be available for shipment to healthcare providers in the U.S. by year-end. HCPs can initiate the process now by visiting www.AlnylamAssist.com and completing and submitting a Start Form.

In August, Alnylam announced a U.S. gastrointestinal (GI) disease education and promotional agreement for Givlaari with Ironwood Pharmaceuticals, Inc., a GI healthcare company. Under the agreement, Alnylam will leverage Ironwood’s leading capabilities in GI to help raise awareness of AHP among gastroenterologists and other healthcare practitioners in the U.S. Ironwood will also participate in Givlaari promotional efforts, augmenting Alnylam’s broader commercialization activities.

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