FDA Approves Leqvio (inclisiran), First-in-Class siRNA to Reduce Low-Density Lipoprotein Cholesterol (LDL-C)

                       In continuation of my update on inclisiran

                             Novartis today announced the US Food and Drug Administration (FDA) approval of Leqvio® (inclisiran), the first and only small interfering RNA (siRNA) therapy to lower low-density lipoprotein cholesterol (also known as bad cholesterol or LDL-C) with two doses a year, after an initial dose and one at three months.

"Leqvio is a revolutionary approach to lower LDL-C, and creates new possibilities for how  healthcare systems can impact cardiovascular disease, a defining public health challenge of our time," said Vas Narasimhan, Novartis CEO. "We now have the opportunity, working together with partners, to provide this first-ever approved LDL-C–lowering siRNA-based therapy to tackle ASCVD at scale across the United States."

Leqvio is indicated in the United States as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality is being explored in clinical trials currently underway.

"ASCVD is a substantial public health burden affecting 30 million Americans," said Norman Lepor, MD, a Los Angeles based cardiologist and a clinical investigator in the Phase III clinical program for Leqvio. "As a first-of-its-kind siRNA therapy, Leqvio works differently than other cholesterol treatments, with twice-yearly dosing that makes it a compelling option for the millions of people with ASCVD already on cholesterol-lowering medications struggling to reach their LDL-C target."

Leqvio reduces the amount of LDL-C in the bloodstream by improving the liver's natural ability to prevent the production of a protein that plays a role in keeping circulating cholesterol levels high6,7. It is a subcutaneous injection given by a healthcare provider with an initial dose, then again at three months, and then every six months1. This approach may help those who have trouble sticking to medicines that are self-administered and have greater dosing frequency. Leqvio will be available in early January 2022.

"People with ASCVD have most likely experienced a heart attack or stroke from high cholesterol, causing a burden on the family and having a negative impact on lives," said Andrea Baer, Executive Director of The Mended Hearts, Inc. "One of the first steps to improving patients' health is to manage high cholesterol and we're encouraged that this new twice-a-year treatment offers a new option." 

The FDA approval was based on results from the comprehensive Phase III ORION-9, -10 and -11 clinical trials, in which all 3,457 participants with ASCVD or HeFH had elevated LDL-C while receiving a maximally tolerated dose of statin therapy2,3. In the Phase III trials at month 17, Leqvio delivered effective and sustained LDL-C reduction of up to 52% vs. placebo and was reported to be well-tolerated with a safety profile shown to be comparable to placebo2,3. The most common side effects were mild to moderate injection site reaction (including pain, redness and rash), joint pain, urinary tract infection, diarrhea, chest cold, pain in legs or arms and shortness of breath2,3.

Novartis has obtained global rights to develop, manufacture and commercialize Leqvio under a license and collaboration agreement with Alnylam Pharmaceuticals, a leader in RNAi therapeutics.

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

FDA Approves Recorlev (levoketoconazole) for the Treatment of Endogenous Hypercortisolemia in Adult Patients With Cushing’s Syndrome

Xeris Biopharma Holdings, Inc. (Nasdaq: XERS), announce  the U.S. Food and Drug Administration (FDA) approval of Recorlev® (levoketoconazole) for the treatment of endogenous hypercortisolemia in adult patients with Cushing’s syndrome for whom surgery is not an option or has not been curative.

“We are thrilled with the FDA's approval of Recorlev as a safe and effective treatment option for patients with endogenous Cushing's syndrome. With this approval, Xeris’ experienced endocrinology-focused commercial organization can begin rapidly working to help address the needs of Cushing’s syndrome patients in the U.S. who are treated with prescription therapy,” said Paul R. Edick, Chairman and CEO of Xeris Biopharma. “Today’s announcement also reinforces the value that we saw in acquiring Strongbridge Biopharma’s attractive rare disease portfolio, which we believe will deliver compelling long-term value to our shareholders. We look forward to making Recorlev commercially available in the first quarter.”

The approval of Recorlev was based upon safety and efficacy data from two positive Phase 3 studies that evaluated a combined study population of 166 patients, which was representative of the adult drug-treated U.S. population with Cushing’s syndrome. The SONICS study met its primary and key secondary endpoints, significantly reducing and normalizing mean urinary free cortisol concentrations without a dose increase. LOGICS, a double-blind, placebo-controlled randomized-withdrawal study that met its primary and key secondary endpoints, confirmed the efficacy and safety of Recorlev in normalizing and maintaining therapeutic response compared with placebo.

“Levoketoconazole (Recorlev) is an important and welcome new therapeutic option for clinicians to help manage patients with endogenous Cushing's syndrome, a severe, potentially life-threatening rare disease, if not appropriately treated, with multisystem signs and symptoms,” said Maria Fleseriu, M.D., FACE, professor of Medicine and Neurological Surgery and director of the Pituitary Center at Oregon Health Sciences University. “In prospective clinical studies, treatment with levoketoconazole was shown to be effective for reducing and normalizing cortisol.”

“Cushing’s syndrome is a rare disease that can be physically and emotionally devastating to the patient. Most patients endure years of symptoms prior to obtaining a diagnosis and are then faced with limited effective treatment options," said Leslie Edwin, president of the Cushing’s Support & Research Foundation. “Today we are excited to see that the long and complicated path of rare drug development has reached FDA approval on a new therapeutic option for our underserved Cushing's community. We are grateful that the researchers worked so diligently for so long to establish the safety and efficacy of this drug. Rare disease patients know the importance of sharing their complicated experiences as ‘expert witnesses’, and we thank Xeris for being an early adherent to this concept. We especially want to thank the clinical trial patients who made this progress possible.”

Xeris is committed to ensuring everyone who needs access to their therapies will receive it. Xeris has created Xeris CareConnection™ to provide a comprehensive program for patients and their caregivers throughout the treatment journey, including financial assistance, one-on-one support, and educational resources. Xeris CareConnection also supports healthcare professionals and their teams through education on access and reimbursement. To get started with Recorlev, reach out to Xeris CareConnection (available Monday–Friday from 8 a.m–7 p.m ET) at 1-844-444-RCLV (7258).

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

https://reference.medscape.com/drug/recorlev-levoketoconazole-4000226

FDA Approves Quviviq (daridorexant) for the Treatment of Adults with Insomnia

Idorsia Ltd (SIX: IDIA) announced  the US Food and Drug Administration (FDA)  approval of  Quviviq (daridorexant) 25 mg and 50 mg for the treatment of adult patients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance1. The FDA approval of Quviviq is based on an extensive clinical program that included 1,854 adults with insomnia at over 160 clinical trial sites across 18 countries. Insomnia, a serious medical condition, is the most common sleep disorder in the US.

Quviviq is a dual orexin receptor antagonist, which blocks the binding of the wake-promoting neuropeptides orexins and is thought to turn down overactive wakefulness, as opposed to treatments that generally sedate the brain.

During the Phase 3 clinical program, Quviviq demonstrated significant improvement versus placebo on objective measures of sleep onset and sleep maintenance, and patient reported total sleep time. Consistent with the US prescribing information, the 50 mg dose of Quviviq, which was evaluated in one of the two pivotal studies, demonstrated a significant reduction in patient reported daytime sleepiness, using a validated instrument. The most common adverse reactions (in at least 5% of patients and greater than placebo) were headache (placebo: 5%, 25 mg: 6%, 50 mg: 7%,) and somnolence or fatigue (placebo: 4%, 25 mg: 6%, 50 mg: 5%).

The FDA has recommended that Quviviq be classified as a controlled substance and it is anticipated to be available to patients in May 2022, following scheduling by the US Drug Enforcement Administration.

Martine Clozel, MD and Chief Scientific Officer of Idorsia, commented:

“After more than 20 years of research and a progressive understanding of the role of orexin in sleep-wake balance and of the potential of orexin receptor antagonism, we designed daridorexant to help address several issues people with insomnia face. Daridorexant properties include a potent inhibition of both orexin receptors, a rapid absorption for sleep onset, and a pharmacokinetic profile such that around 80% of daridorexant has been eliminated after a night of sleep to help minimize residual effects.”

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

https://clinicaltrials.gov/ct2/show/NCT04250506

FDA Approves Ryaltris (mometasone and olopatadine) Nasal Spray for Seasonal Allergic Rhinitis

In continuation of my update on olopatadine

Glenmark Pharmaceuticals Limited, announced the  FDA approval of its New Drug Application (NDA) for Ryaltris, an innovative, fixed- dose (metered), prescription, combination drug product nasal spray for the treatment of symptoms of Seasonal Allergic Rhinitis in adults and pediatric patients 12 years of age and older in the United States.

mometasone

Olopatadine,

The FDA's approval of Ryaltris™ represents a major milestone for Glenmark and clearly supports our efforts to bring innovative treatment options in our key therapeutic areas," said Robert Crockart, Chief Commercial Officer of Glenmark Pharmaceuticals Limited. "With this NDA approval, we look forward to bringing this new medicine to physicians and their patients for the treatment of symptoms of seasonal allergic rhinitis, including nasal and ocular symptoms."

Ryaltris™ will be marketed and distributed in the United States (US) by Hikma Specialty U.S.A., Inc., as part of its exclusive licensing agreement with Glenmark Specialty S.A (Switzerland).

Ryaltris is a metered, fixed-dose, aqueous suspension, prescription drug product nasal spray approved by the FDA for the treatment of symptoms associated with Seasonal Allergic Rhinitis. Each unit of Ryaltris™ nasal spray contains 665 mcg of olopatadine hydrochloride, a histamine-1(H1)-receptor inhibitor, and 25 mcg of mometasone furoate, a corticosteroid. The combination drug product nasal spray is indicated for the treatment of symptoms associated with seasonal allergic rhinitis in adults and pediatric patients 12 years of age and older. The safety and effectiveness of Ryaltris™ in pediatric patients younger than 12 years of age has not been established.

The recommended daily dose for Ryaltris is 2 sprays in each nostril twice daily.

Ryaltris will be marketed and distributed in the United States through their partner Hikma Specialty U.S.A. Inc., Columbus, OH.

Ryaltris has been approved and is marketed in Australia, the Czech Republic, Poland, Russia, South Africa, Ukraine, the United Kingdom, and Uzbekistan. In April 2021, Glenmark concluded the DCP regulatory procedure in Europe, enabling approval in 17 countries across EU and UK.

Glenmark has entered into commercial agreements with several partners around the world, including Menarini for the commercialization of Ryaltris™ in select EU markets, and with Bausch Health in Canada (where it is under review by Health Canada).

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

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

FDA Approves Ryaltris (mometasone and olopatadine) Nasal Spray for Seasonal Allergic Rhinitis

FDA Approves Cibinqo (abrocitinib) for Adults with Moderate-to-Severe Atopic Dermatitis

Pfizer Inc. (NYSE: PFE) announced  the United States (U.S.) Food and Drug Administration (FDA) approval of  Cibinqo (abrocitinib), an oral, once-daily, Janus kinase 1 (JAK1) inhibitor, for the treatment of adults living with refractory, moderate-to-severe atopic dermatitis (AD) whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable.

Cibinqo is approved at the recommended doses of 100 mg and 200 mg, with the 200 mg dose being recommended for patients who are not responding to the 100 mg dose. Additionally, a 50 mg dose was approved to treat moderate-to-severe AD specifically in patients with moderate renal impairment (kidney failure), certain patients receiving treatment with inhibitors of cytochrome P450 (CYP) 2C19, or patients who are known or suspected to be poor metabolizers of CYP2C19. For patients with moderate renal impairment who are not responding to 50 mg once daily, 100 mg once daily may also be prescribed.

“The reality for patients living with chronic inflammatory skin disease such as moderate-to-severe atopic dermatitis is that many experience debilitating symptoms that are not managed by current treatment options. Today’s approval of Cibinqo will provide an important new oral option that could help those who have yet to find relief,” said Jonathan Silverberg, MD, PhD, MPH, Department of Dermatology, The George Washington University School of Medicine and Health Sciences. “In multiple large-scale clinical trials, Cibinqo demonstrated strong efficacy at clearing skin, improving itch, and managing the extent and severity of eczema, offering a benefit-risk profile that supports the use of this treatment in the FDA-approved patient population.”

The FDA approval was based on results of five clinical trials from a large-scale clinical trial program of more than 1,600 patients. The safety and efficacy of Cibinqo was evaluated in three randomized, placebo-controlled, Phase 3 trials. Additionally, safety was evaluated through a randomized, placebo-controlled, dose-ranging trial and an ongoing long-term open-label extension trial. Across the trials, Cibinqo demonstrated a consistent safety profile and profound improvements in skin clearance, extent of disease, and severity, as well as rapid improvement in itch after two weeks, for some people living with AD versus placebo. In addition, a higher proportion of subjects treated with Cibinqo in two monotherapy trials achieved improvement in itching at week 12 compared to placebo.

“The FDA’s approval offers hope to the millions of patients across the U.S. who are suffering daily with an immuno-inflammatory condition that can cause intense and persistent itching, pain, discomfort, and distress if left uncontrolled,” said Mike Gladstone, Global President of Pfizer Inflammation & Immunology. “Cibinqo, an efficacious once-daily pill, is a medical breakthrough made possible by Pfizer researchers and the people living with moderate-to-severe atopic dermatitis who participated in our clinical trials.”

“Atopic dermatitis is so much more than just a rash, and it goes beyond the surface of the skin. It’s a chronic condition that can both significantly disrupt patients’ daily lives and negatively impact their emotional well-being,” said Julie Block, President and CEO, National Eczema Association. “We appreciate Pfizer’s commitment to this resilient patient community and eagerly await the positive impact Cibinqo could have on the treatment landscape for moderate-to-severe atopic dermatitis.”

The most common adverse events reported in ≥5% of patients with Cibinqo included nasopharyngitis (12.4% with Cibinqo 100 mg, 8.7% with Cibinqo 200 mg, and 7.9%, with placebo), nausea (6%, 14.5%, and 2.1%, respectively), and headache (6%, 7.8%, and 3.5%, respectively).

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

https://www.clinicaltrials.gov/ct2/show/NCT04345367

FDA Approves Fleqsuvy (baclofen oral suspension) for the Treatment of Spasticity

Azurity Pharmaceuticals, Inc., a private specialty pharmaceutical company, focused on developing innovative products to meet the unique needs of patients with underserved conditions,  announced the U.S. Food and Drug Administration (FDA) approval of Fleqsuvy™ (baclofen oral suspension), 25 mg per 5 mL (5 mg/mL), Concentrated Formulation for the treatment of spasticity from multiple sclerosis (MS) or patients with spinal cord injuries and other spinal cord diseases.

“The approval of Fleqsuvy™ represents our commitment to providing innovative alternative formulations that address individualized patient needs. The clinical profile of Fleqsuvy™ allows for a tailored and flexible approach to dosing for patients suffering from spasticity, a debilitating symptom that may impact daily functioning,” said Amit Patel, Chairman and CEO of Azurity Pharmaceuticals.

Nearly 1 million people are living with Multiple Sclerosis in the United States.1 Spasticity is a commonly reported symptom for MS, with an estimated prevalence of spasticity of 67%.2 Due to the severity of spasticity resulting from multiple sclerosis or patients with spinal cord injuries and other spinal cord diseases, dosing becomes paramount to providing appropriate relief. Furthermore, dysphagia is commonly experienced, affecting approximately 43% of multiple sclerosis patients3 and 16-30% of patients with spinal cord injuries. Fleqsuvy™ provides an option as a baclofen oral liquid medication at an effective dose for patients who have trouble swallowing pills or prefer a liquid formulation. As the most concentrated FDA-approved oral liquid baclofen formulation, Fleqsuvy™ allows for the lowest volume to be prescribed for patients, which can be an important consideration for those suffering from dysphagia.

About Fleqsuvy™

Fleqsuvy™ is a grape-flavored oral suspension formulation of baclofen approved by the FDA for the treatment of spasticity resulting from multiple sclerosis, particularly for the relief of flexor spasms and concomitant pain, clonus, and muscular rigidity. It may also be of some value in patients with spinal cord injuries and other spinal cord diseases. Fleqsuvy™ contains 25 mg per 5 mL (5 mg/mL) and is supplied in bottles of either 120mL or 300mL. Limitations of Use: Fleqsuvy™ is not indicated in the treatment of skeletal muscle spasm resulting from rheumatic disorders.

FDA Approves Pyrukynd (mitapivat) as First Disease-Modifying Therapy for Hemolytic Anemia in Adults with Pyruvate Kinase Deficiency

Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism pioneering therapies for genetically defined diseases, announced  the   U.S. Food and Drug Administration (FDA) approval of Pyrukynd  (mitapivat) in the U.S. for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency, a rare, debilitating, lifelong hemolytic anemia. Pyrukynd  is a first-in-class, oral PK activator and the first approved disease-modifying therapy for this disease.

“The successful ACTIVATE and ACTIVATE-T studies demonstrate the impact of mitapivat in significantly improving hemolysis and anemia in PK deficiency,” said Hanny Al-Samkari, M.D., hematologist and clinical investigator at the Mass General Cancer Center and Harvard Medical School, and an investigator in these pivotal Phase 3 studies. “The FDA approval of mitapivat, a targeted agent and first disease-modifying medication in PK deficiency, is an encouraging step forward for these patients that addresses a significant unmet need.”

“Pyrukynd® is the first approved therapy for PK deficiency and marks an important milestone for these patients, who may face tremendous challenges and debilitating symptoms throughout the course of this lifelong disease,” said Rachael Grace, M.D., MMSc, pediatric hematologist, director of hematology clinical research at Boston Children’s Hospital and an investigator in the Phase 2 DRIVE PK and Phase 3 ACTIVATE studies. “Partnering with Agios and the PK deficiency community to improve understanding of the natural history of this rare disease and bring a new medicine to patients has been an honor, and I look forward to additional collaboration in the future.”

“I am so grateful that Pyrukynd® has been approved for PK deficiency. As both patient and caregiver, I spent the majority of my life feeling alone in this disease and never thought I would see a medicine approved,” said Kim Hall, who was diagnosed with PK deficiency in 1969 and is the mother of two adult daughters living with PK deficiency. All three women participated in the Phase 3 Pyrukynd® PK deficiency clinical program. “The experience of being part of the clinical trials has been impactful because of the connections we have built with other patients, healthcare providers and Agios colleagues who understand PK deficiency and are actively working to improve patients’ lives.”

“For more than a decade, we have been pioneering the science of PK activation in order to bring Pyrukynd® to people with PK deficiency and provide them with the first medication approved specifically to address this rare, debilitating blood disorder,” said Jackie Fouse, Ph.D., chief executive officer at Agios. “We remain committed to partnering with patients, caregivers, advocates and healthcare providers to ensure that the impact of Pyrukynd® is maximized through robust support, education and access programs. These connections have fueled today’s tremendous milestone for the PK deficiency community. Each of us at Agios is dedicated to making a difference for people with PK deficiency, as well as to expanding the reach of Pyrukynd® and our clinical and research programs to many more patients with genetically defined diseases around the world.”

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

https://clinicaltrials.gov/ct2/show/NCT05031780

FDA Approves Norliqva (amlodipine) Oral Solution for Hypertension and Coronary Artery Disease

In continuation of my update on amlodipine besylate

The U.S. Food and Drug Administration has approved Norliqva (amlodipine) oral solution for the treatment of:

• Hypertension in adults and children 6 years and older, to lower blood pressure.
• Coronary artery disease [Chronic Stable Angina, Vasospastic Angina (Prinzmetal’s or Variant Angina) and Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction <40%.]

• Amlodipine is a widely used long-acting calcium channel blocker first approved by the FDA thirty years ago. It is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure, and is thought to reduce the total peripheral resistance and inhibit coronary spasm to relieve angina.

  Amlodipine is FDA approved under the brand names Norvasc (amlodipine oral tablets) and Katerzia (amlodipine oral suspension), and the oral tablets are also available as generics.

  Norliqva is supplied as a peppermint flavored oral solution containing 1 mg/mL amlodipine as the besylate salt. It is administered once daily.

  Most common adverse reactions to amlodipine include edema, dizziness, flushing and palpitation which occurred in a dose related manner. Other adverse reactions not clearly dose-related but reported with an incidence >1.0% are fatigue and nausea.

https://www.webmd.com/drugs/2/drug-5891/amlodipine-oral/details

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