FDA Approves Valtoco (diazepam nasal spray) as a Seizure Rescue Treatment

Neurelis, Inc.,  announced that the U.S. Food and Drug Administration (FDA) has approved Valtoco (diazepam nasal spray) as an acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in people with epilepsy 6 years of age and older. The unique formulation of Valtoco incorporates Intravail® for consistent and reliable absorption.

“Cluster or acute repetitive seizures are challenging to treat and highly disruptive in the lives of people with epilepsy,” said Neurelis President and CEO Craig Chambliss. “Valtoco was developed to provide an effective combination of reliability, safety and tolerability in a ready-to-use nasal spray. This is a defining moment for Neurelis as Valtoco is our first FDA-approved product. We are excited that we can now offer this treatment option to patients and provide additional support to the epilepsy community.”

Chambliss added that Valtoco was also granted seven years of Orphan Drug Exclusivity by the FDA Office of Orphan Products Development.

Valtoco is a proprietary formulation of diazepam incorporating the Science of Intravail. Intravail transmucosal absorption enhancement technology enables the non-invasive delivery of a broad range of protein, peptide and small molecule drugs. In the United States, there are over 3.4 million people with epilepsy, with approximately 200,000 new patients diagnosed each year. Despite the availability of chronic, daily oral medications to control epilepsy, a significant number of these patients continue to experience seizures. Of these uncontrolled patients, as many as 170,000 are at risk for episodes of frequent seizure activity, also known as cluster or acute repetitive seizures, representing a significant unmet need in the epilepsy community.

“This is an important development in the epilepsy community,” said R. Edward Hogan, MD, Director of the Washington University and Barnes-Jewish Epilepsy Center in St. Louis. “Most seizures that require intervention are treated in an inconvenient manner. To be able to reliably treat seizure activity when and where it happens with a caregiver-administered option like Valtoco is a significant step forward. The availability of Valtoco may positively impact the lives of thousands of people with epilepsy who experience cluster or acute repetitive seizures and their care partners.”

In a long-term, open-label, repeat dose, clinical trial, the safety of Valtoco was evaluated: over 130 patients were enrolled and more than 2,000 seizures were treated. The clinical trial included patients aged 6 and above. “Until recently, approved treatment outside of medical care settings was only available as a rectally administered medication,” Dr. Hogan said. “The FDA approval of diazepam nasal spray is a significant advancement for the epilepsy community.”

Enrique Carrazana, MD, Chief Scientific Officer for Neurelis, notes that Valtoco was generally safe and well tolerated during clinical studies. The most common adverse reactions (at least 4%) were somnolence, headache, and nasal discomfort.

Jacqueline A. French, MD, professor in the Department of Neurology at NYU Langone Health’s Comprehensive Epilepsy Center and Chief Medical & Innovation Officer for the Epilepsy Foundation, commented, “One of the goals of rescue therapy is to treat seizure clusters, recognized as medical emergencies, before negative consequences may be experienced. These consequences may include injury and seizure progression to status epilepticus. Having a seizure rescue treatment that is generally safe, reliable and ready-to-use is very empowering. We encourage all epilepsy patients to work with their doctors to make sure they have a seizure rescue treatment plan in place.”

Indication

Valtoco (diazepam nasal spray) is indicated for the acute treatment of intermittent, stereotypic episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in patients with epilepsy 6 years of age and older.

https://www.chemdiv.com/valtoco-is-approved-by-fda/

FDA Approves Numbrino (cocaine hydrochloride) Nasal Solution for Nasal Anesthesia

In continuation of my update on Cocaine

Lannett Company, Inc. (NYSE: LCI),  announced that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA), submitted under the 505(b)(2) regulatory pathway, for Cocaine Hydrochloride (HCl) Nasal Solution 4% (40 mg/mL), the company's branded local anesthetic product.Lannett Company, Inc. (NYSE: LCI) today announced that the U.S. Food and Drug Administration (FDA) has approved the New Drug Application (NDA), submitted under the 505(b)(2) regulatory pathway, for Cocaine Hydrochloride (HCl) Nasal Solution 4% (40 mg/mL), the company's branded local anesthetic product.

"The FDA's approval of our Cocaine HCl product, the first NDA approval to include full clinical trials in the company's history, marks a major milestone in Lannett's 70+ years of operations," said Tim Crew, chief executive officer of Lannett. "We believe the product has the potential to be an excellent option for the labeled indication. We expect to launch the product shortly, under the brand name Numbrino®."

Numbrino® (cocaine hydrochloride) nasal solution is an ester local anesthetic indicated for the introduction of local anesthesia of the mucous membranes for diagnostic procedures and surgeries on or through the nasal cavities of adults. The 505(b)(2) NDA submission was supported by two Phase III, randomized, double-blind, placebo-controlled, multicenter studies in several hundred patients, as well as a Phase I pharmacokinetic study.

About Lannett Company, Inc.:

Lannett Company, founded in 1942, develops, manufactures, packages, markets and distributes generic pharmaceutical products for a wide range of medical indications. For more information, visit the company's website at www.lannett.com.

This news release contains certain statements of a forward-looking nature relating to future events or future business performance.  Any such statement, including, but not limited to, successfully commercializing Numbrino®, whether expressed or implied, is subject to market and other conditions, and subject to risks and uncertainties which can cause actual results to differ materially from those currently anticipated due to a number of factors which include, but are not limited to, the risk factors discussed in the Company's Form 10-K and other documents filed with the SEC from time to time, including the prospectus supplement related to the proposed offering to be filed with the SEC.  These forward-looking statements represent the Company's judgment as of the date of this news release.  The Company disclaims any intent or obligation to update these forward-looking statements.

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

FDA Approves Vyondys 53 (golodirsen) Injection for the Treatment of Duchenne Muscular Dystrophy (DMD) in Patients Amenable to Skipping Exon 53

In continuation of my update on oligonucleotide.

Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that the U.S. Food and Drug Administration (FDA) has approved Vyondys 53™ (golodirsen). Vyondys 53 is an antisense oligonucleotide from Sarepta’s phosphorodiamidate morpholino oligomer (PMO) platform, indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients with a confirmed mutation amenable to exon 53 skipping. This indication is based on a statistically significant increase in dystrophin production in skeletal muscle observed in patients treated with Vyondys 53, which is reasonably likely to predict clinical benefit for those patients who are exon 53 amenable. Consistent with the accelerated approval pathway, the continued approval of Vyondys 53 may be contingent on confirmation of a clinical benefit in this post-marketing confirmatory trial.

Sarepta’s placebo-controlled, post-marketing confirmatory trial to support the Vyondys 53 accelerated approval – titled ESSENCE – is currently enrolling and expected to conclude by 2024.

Hypersensitivity reactions, including rash, pyrexia (fever), pruritis, urticaria (hives), dermatitis, and skin exfoliation have occurred in patients who were treated with Vyondys 53. Renal toxicity was observed in animal studies. Although not observed in the clinical studies with Vyondys 53, renal toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. The most common adverse reactions that occurred in at least 20% of Vyondys 53-treated patients and more frequently than in placebo-treated patients were headache (41%), pyrexia (41%), fall (29%), abdominal pain (27%), nasopharyngitis (27%), cough (27%), vomiting (27%), and nausea (20%).

Following a New Drug Application (NDA) submission to and review by the Division of Neurology Products (the Review Division) for Vyondys 53, which the Review Division recommended for approval, the Office of Drug Evaluation 1 issued a complete response letter (CRL) in August of 2019. Thereafter, Sarepta made a formal dispute resolution request as outlined in relevant FDA Guidance. With the support of the Review Division, the matters raised in the CRL were rapidly evaluated and resolved by Dr. Peter Stein, Director of the Office of New Drugs (OND). OND granted the Company’s appeal and Sarepta re-submitted its NDA to the Review Division, which worked expeditiously to review and approve Vyondys 53.

“Today is monumental for Sarepta and, more importantly, for the DMD community,” said Doug Ingram, president and chief executive officer, Sarepta. “Vyondys 53, our second approved exon-skipping RNA therapy for DMD, may treat up to 8% of the DMD community, representing those patients who have a confirmed exon 53 amenable mutation. Along with EXONDYS 51® (eteplirsen), we now offer treatment options for approximately 20% of those with DMD in the U.S.”

Ingram continued, “In the span of four months, we commenced and completed the formal dispute resolution process culminating in the grant of our appeal, resubmitted our NDA and obtained an approval – a great benefit to DMD patients awaiting treatment. This unprecedented timing could not have been achieved without the commitment of the Review Division under the leadership of Dr. Billy Dunn, and the Office of New Drugs, which expeditiously heard and granted our appeal. Along with the DMD community, we owe our gratitude to both the Review Division and the OND for their objective, evidence-based approach to this review, for their fairness, and for the sense of urgency with which they addressed and resolved the CRL and granted this approval.”

“With the approval of Vyondys 53, up to another 8% of Duchenne families will have a therapy to treat this devastating disease,” said Pat Furlong, founding president and chief executive officer, Parent Project Muscular Dystrophy (PPMD). “For 25 years, PPMD has been working with researchers, clinicians, industry, and the Duchenne community to find treatments for all people living with Duchenne. And while we need to ensure that these approved therapies are accessible for patients, today we celebrate this approval and thank Sarepta for their continued leadership in the fight to end Duchenne.”

Vyondys 53 is priced at parity to EXONDYS 51, the price of which has not increased since its launch in 2016. Patients and physicians can access more information at www.SareptAssist.com or by calling 1-888-727-3782.

About Vyondys 53

Vyondys 53 is an antisense oligonucleotide indicated for the treatment of Duchenne muscular dystrophy in patients who have a confirmed mutation of the DMD gene that is amenable to exon 53 skipping. Vyondys 53 uses Sarepta’s proprietary phosphorodiamidate morpholino oligomer (PMO) chemistry and exon-skipping technology to bind to exon 53 of dystrophin pre-mRNA, resulting in exclusion, or “skipping,” of this exon during mRNA processing in patients with genetic mutations that are amenable to exon 53 skipping. Exon skipping is intended to allow for production of an internally truncated dystrophin protein.

https://www.rxlist.com/vyondys-53-drug.htm

FDA Approves Arazlo (tazarotene) Lotion for the Topical Treatment of Acne Vulgaris

In continuation of my update on tazarotene

Bausch Health Companies Inc. (NYSE/TSX: BHC) and its dermatology business, Ortho Dermatologics, one of the largest prescription dermatology health care businesses,  announced the U.S. Food and Drug Administration (FDA)   approval of   the New Drug Application for Arazlo (tazarotene) Lotion, 0.045%, for the topical treatment of acne vulgaris in patients nine years of age and older.1 Arazlo is the first tazarotene acne treatment available in a lotion form, and has been shown to provide strong efficacy with favorable tolerability.

"Today's approval of Arazlo showcases our continued commitment to expanding our acne portfolio to help the approximately 50 million Americans who are impacted by this prevalent skin condition," said Bill Humphries, president, Ortho Dermatologics. "As our fourth FDA approval in just 14 months, Arazlo will provide dermatologists the efficacy expected of tazarotene in a new formulation that helps minimize the dryness and irritation historically associated with tazarotene use, which can cause many acne patients to discontinue treatment. We are purposely timing the launch of Arazlo to coincide with the start of acne season in the first half of 2020."

Retinoids like tazarotene are a core component of acne treatment. However, a common barrier to their use is that treatment with retinoids is often associated with skin irritation, such as dryness.2 In a head-to-head study, Arazlo demonstrated similar efficacy as Tazorac (tazarotene) Cream 0.1% with about half the adverse events.2  The most frequent adverse events reported with Arazlo (≥1%) were application site pain, dryness, exfoliation, erythema and pruritus.1

"Many of my patients with moderate to severe acne can benefit from the efficacy of tazarotene, but struggle to stay on treatment due to tolerability issues," said Emil Tanghetti, M.D., lead Arazlo study investigator and founder, Center for Dermatology and Laser Surgery, Sacramento, Calif. "Tazarotene has typically been reserved only for patients with severe acne, but offering it in a well-tolerated lotion formulation that includes hydrating agents can help more patients with most types of acne take advantage of its efficacy. I look forward to adding Arazlo to my practice armamentarium."

Arazlo Comprehensive Clinical Data

The FDA approval for Arazlo was based on data from two Phase 3 multicenter, randomized, double-blind, vehicle-controlled clinical trials in 1,614 patients with moderate to severe acne. In both Phase 3 studies, all primary efficacy endpoints were met with statistical significance (p<.001). Arazlo was also shown to be generally well-tolerated in the clinical study population.

In a Phase 2, head-to-head study, Arazlo and Tazorac (tazarotene) Cream 0.1% showed similar treatment success rates and similar reductions in both inflammatory and non-inflammatory lesions over 12 weeks. While there were no significant differences in patient satisfaction or quality of life between the two treatments and both were well-tolerated, there were numerically about double the number of treatment-related adverse events with Tazorac (5.6 percent with Tazorac versus 2.9 percent with Arazlo).

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

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

In continuation of my update on pexidartinib

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.

The FDA granted this application Breakthrough Therapy designation and Priority Reviewdesignation. Turalio also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases. The FDA granted the approval of Turalio to Daiichi Sanky.

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

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