FDA Approves Qulipta (atogepant) Oral CGRP Receptor Antagonist for the Preventive Treatment of Migraine

In continuation of my update on Qulipta (atogepant),  AbbVie (NYSE: ABBV)   announced  the U.S. Food and Drug Administration (FDA) approval of  Qulipta (atogepant) for the preventive treatment of episodic migraine in adults. Qulipta is the first and only oral calcitonin gene-related peptide (CGRP) receptor antagonist (gepant) specifically developed for the preventive treatment of migraine.

"Millions of people living with migraine often lose days of productivity each month because attacks can be debilitating. Qulipta can help by reducing monthly migraine days with a once-daily, oral dose that works quickly and continuously," said Michael Severino, M.D., vice chairman and president, AbbVie. "We are proud that AbbVie is now the only pharmaceutical company to offer three products across the full spectrum of migraine treatment, which include preventive therapies for chronic and episodic migraine and an acute treatment for migraine attacks."

The approval is supported by data from a robust clinical program evaluating the efficacy, safety and tolerability of Qulipta in nearly 2,000 patients who experienced 4 to 14 migraine days per month, including the pivotal Phase 3 ADVANCE study — which was published in The New England Journal of Medicine — the pivotal Phase 2b/3 study, and the Phase 3 long-term safety study.

"When I have a migraine attack, my 5-year-old daughter doesn't understand why I can't take her to a birthday party or to the park. It's heartbreaking when I have to tell her I need to be away from her because my eyes feel like they're going to explode out of my head," said Kelsi Owens, an ADVANCE trial participant who has lived with migraine for nearly three decades. "During the trial while taking Qulipta, I had many fewer migraine days. For the first time ever, I don't have difficulty doing my daily activities and I don't have to worry as much that a migraine attack will cause me to miss important events with family and friends."

Migraine is a complex disease with recurrent attacks that are often incapacitating and characterized by severe, throbbing headache pain as well as compounding associated symptoms like extreme sensitivity to light, sound or nausea. It is highly prevalent, affecting more than 1 billion people worldwide, including 39 million people in the U.S. alone, and is the highest cause of disability worldwide for people under 50 years of age.

"This approval reflects a broader shift in the treatment and management paradigm for the migraine community. Qulipta provides a simple oral treatment option specifically developed to prevent migraine attacks and target CGRP, which is believed to be crucially involved in migraine in many patients," said Peter J. Goadsby, M.D., Ph.D., D.Sc., neurologist and professor at University of California, Los Angeles, and King's College, London, who earned the prestigious Brain Prize in 2021 for his revolutionary research about CGRP's role in migraine attacks and co-authored the ADVANCE study.

"I'm particularly encouraged by the convenience of the oral daily use of Qulipta, its rapid onset of significant efficacy, and its safety and tolerability as well as its high patient response rates. This is a milestone in preventive migraine treatment that I hope will help many patients for years to come," Goadsby said.

Highlights from the clinical program supporting the approval and additional data analysis include:

• In the pivotal Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group ADVANCE trial, the primary endpoint was change from baseline in mean monthly migraine days across the 12-week treatment period. All Qulipta dose groups met the primary endpoint and demonstrated statistically significant reductions in mean monthly migraine days compared to placebo. Patients treated with 60 mg of Qulipta across 12 weeks experienced a 4.2-day reduction from baseline of 7.8.
• A key secondary endpoint in the ADVANCE trial measured the proportion of patients that achieved a ≥50% reduction in monthly migraine days across the 12-week treatment period. The trial demonstrated that 56%/59%/61% of patients in the 10 mg/30 mg/60 mg Qulipta arms, respectively, achieved a 50-100% reduction, compared to 29% of patients in the placebo arm (all dose groups vs. placebo, p<.001).
• All doses were well tolerated in the ADVANCE trial and pivotal Phase 2b/3 clinical trial evaluating the efficacy, safety and tolerability of orally administered Qulipta. Adverse reactions in both studies (incidence at least 2% and greater than placebo) included nausea (5-9% across all doses versus 3% for placebo), constipation (6% across all doses versus 1% for placebo), fatigue/somnolence (4-6% across all doses versus 3% for placebo) and decreased appetite (1-2% across all doses versus <1% for placebo). The adverse reactions that most commonly led to discontinuation were constipation (0.5%), nausea (0.5%) and fatigue/somnolence (0.5%).
• The pivotal Phase 2b/3 trial demonstrated that all active treatment arms met the primary efficacy endpoint of change from baseline in mean monthly migraine days with significantly greater reductions in mean monthly migraine days across the 12-week treatment period for all three Qulipta treatment groups compared with placebo. All three Qulipta treatment groups also met the secondary efficacy endpoint of change from baseline in mean monthly headache days.

FDA Approves Opzelura (ruxolitinib) Cream for the Treatment of Atopic Dermatitis (AD)

In continuation of my update on Opzelura (ruxolitinib)  , Incyte (Nasdaq:INCY)announced  the U.S. Food and Drug Administration (FDA)  approval Opzelura™ (ruxolitinib) cream for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable. Opzelura is the first and only topical formulation of a JAK inhibitor approved in the United States. Research shows dysregulation of the JAK-STAT pathway contributes to key features of AD such as itch, inflammation and skin barrier dysfunction.

“Atopic dermatitis is a chronic immune-mediated disease that can be challenging to manage. Many patients do not respond well to existing treatments and have uncontrolled disease,” said Jonathan Silverberg, M.D., Ph.D., M.P.H., Associate Professor of Dermatology and Director of Clinical Research and Contact Dermatitis at The George Washington University School of Medicine and Health Sciences. “As a clinician, I am excited to have a non-steroidal topical cream like Opzelura.”

“The approval of Opzelura is an important advancement in the treatment of AD, and we are pleased to offer a novel topical treatment option that targets a pathway believed to be a source of inflammation,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “At Incyte, we are committed to transforming the treatment of immune-mediated dermatologic conditions like AD. We look forward to bringing Opzelura to the patient community and also continuing to explore its potential in other challenging skin diseases.”

The FDA approval was based on data from the TRuE-AD (Topical Ruxolitinib Evaluation in Atopic Dermatitis) clinical trial program, consisting of two randomized, double-blind, vehicle-controlled Phase 3 studies (TRuE-AD1 and TRuE-AD 2) evaluating the safety and efficacy of Opzelura in more than 1,200 adolescents and adults with mild to moderate AD. Results from the studies showed patients experienced significantly clearer skin and itch reduction when treated with Opzelura cream 1.5% twice daily (BID), compared to vehicle (non-medicated cream):

• Significantly more patients treated with Opzelura achieved Investigator’s Global Assessment (IGA) Treatment Success (IGA-TS, primary endpoint) at Week 8 (defined as an IGA score of 0 [clear] or 1 [almost clear] with at least a 2-point improvement from baseline): 53.8% in TRuE-AD1 and 51.3% in TRuE-AD2, compared to vehicle (15.1% in TRuE-AD1, 7.6% in TRuE-AD2; P<0.0001).
• Significantly more patients treated with Opzelura experienced a clinically meaningful reduction in itch from baseline at Week 8, as measured by a ≥4-point reduction in the itch Numerical Rating Scale (itch NRS4): 52.2% in TRuE-AD1 and 50.7% in TRuE-AD2, compared to vehicle (15.4% in TRuE-AD1, 16.3% in TRuE-AD2; P<0.0001), among patients with an NRS score of at least 4 at baseline.

In clinical trials, the most common (≥1%) treatment-emergent adverse reactions in patients treated with Opzelura were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil count increased, urticaria, folliculitis, tonsillitis and rhinorrhea2. See Important Safety Information below, including Boxed Warnings for serious infections, mortality, malignancy, major adverse cardiovascular events and thrombosis, seen with JAK inhibitors for inflammatory conditions.

“It can be hard for people to fully appreciate how difficult AD can be and the tremendous impact it has on patients,” said Julie Block, President & CEO, National Eczema Association. “The chronic itch is difficult to cope with and related sleep issues can be exhausting. Many patients and their dermatologists are looking for additional options to meet current unmet needs in the management of AD. The approval of Opzelura is exciting news, and we welcome a new treatment option for our community.”

AD is a chronic skin disease affecting more than 21 million people aged 12 years and older in the U.S. and is characterized by inflammation and itch3. Signs and symptoms include irritated and itchy skin that can cause red lesions that may ooze and crust. People with AD are also more susceptible to bacterial, viral and fungal infections.

FDA Approves Exkivity (mobocertinib) for EGFR Exon20 Insertion+ Non-Small Cell Lung Cancer (NSCLC)

Takeda Pharmaceutical Company Limited  announced   the U.S. Food and Drug Administration (FDA)  approval of  Exkivity (mobocertinib) for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. Exkivity, which was granted priority review and received Breakthrough Therapy Designation, Fast Track Designation and Orphan Drug Designation from the FDA, is the first and only approved oral therapy specifically designed to target EGFR Exon20 insertion mutations. This indication is approved under Accelerated Approval based on overall response rate (ORR) and DoR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

“The approval of Exkivity introduces a new and effective treatment option for patients with EGFR Exon20 insertion+ NSCLC, fulfilling an urgent need for this difficult-to-treat cancer,” said Teresa Bitetti, president, Global Oncology Business Unit, Takeda. “Exkivity is the first and only oral therapy specifically designed to target EGFR Exon20 insertions, and we are particularly encouraged by the duration of the responses observed with a median of approximately 1.5 years. This approval milestone reinforces our commitment to meeting the needs of underserved patient populations within the oncology community.”

The FDA simultaneously approved Thermo Fisher Scientific’s Oncomine Dx Target Test as an NGS companion diagnostic for Exkivity to identify NSCLC patients with EGFR Exon20 insertions. NGS testing is critical for these patients, as it can enable more accurate diagnoses compared to polymerase chain reaction (PCR) testing, which detects less than 50% of EGFR Exon20 insertions.

“EGFR Exon20 insertion+ NSCLC is an underserved cancer that we have been unable to target effectively with traditional EGFR TKIs,” said Pasi A. Jänne, MD, PhD, Dana Farber Cancer Institute. “The approval of Exkivity (mobocertinib) marks another important step forward that provides physicians and their patients with a new targeted oral therapy specifically designed for this patient population that has shown clinically meaningful and sustained responses.”

“Patients with EGFR Exon20 insertion+ NSCLC have historically faced a unique set of challenges living with a very rare lung cancer that is not only underdiagnosed, but also lacking targeted treatment options that can improve response rates,” said Marcia Horn, executive director, Exon 20 Group at ICAN, International Cancer Advocacy Network. “As a patient advocate working with EGFR Exon20 insertion+ NSCLC patients and their families every day for nearly five years, I am thrilled to witness continued progress in the fight against this devastating disease and am grateful for the patients, families, healthcare professionals and scientists across the globe who contributed to the approval of this promising targeted therapy.”

The FDA approval is based on results from the platinum-pretreated population in the Phase 1/2 trial of Exkivity, which consisted of 114 patients with EGFR Exon20 insertion+ NSCLC who received prior platinum-based therapy and were treated at the 160 mg dose. Results were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting from the Phase 1/2 trial and demonstrated a confirmed ORR of 28% per independent review committee (IRC) (35% per investigator) as well as a median DoR of 17.5 months per IRC, a median overall survival (OS) of 24 months and a median progression-free survival (PFS) of 7.3 months per IRC.

FDA Approves Welireg (belzutifan) for the Treatment of Patients With Certain Types of Von Hippel-Lindau (VHL) Disease-Associated Tumors

Merck (NYSE: MRK),  announced that the U.S. Food and Drug Administration (FDA) has approved 'Welireg, an oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The recommended dose of Welireg (40 mg tablets) is 120 mg once daily until disease progression or unacceptance toxicity. The approval is based on results from the open-label Study 004 trial (N=61), where the major efficacy endpoint was overall response rate (ORR) in patients with VHL-associated RCC.

Welireg is the first HIF-2α inhibitor therapy approved in the U.S. As an inhibitor of HIF-2α, Welireg reduces transcription and expression of HIF-2α target genes associated with cellular proliferation, angiogenesis and tumor growth.

The Welireg label contains a boxed warning that exposure to Welireg during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of Welireg. Advise patients of these risks and the need for effective non-hormonal contraception. Welireg can render some hormonal contraceptives ineffective. Welireg can cause severe anemia that can require a blood transfusion. Monitor for anemia before initiation of Welireg and periodically throughout treatment. Welireg can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of and periodically throughout treatment with Welireg. For more information, see "Selected Safety Information" below.

“VHL disease is a rare and serious condition. Until today, there were no systemic therapies approved to help treat patients diagnosed with certain types of VHL-associated tumors,” said Dr. Eric Jonasch, principal investigator of Study 004 and professor, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. “The approval of Welireg, which is based on data showing an overall response rate across three different types of VHL-associated tumors, addresses this significant unmet need by introducing a new option for physicians and their patients impacted by this disease.”

“Welireg is the first and only approved systemic therapy for patients with certain types of VHL-associated tumors, representing an important new treatment option for patients affected by this rare condition,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “Today’s approval of Welireg is a significant milestone and is a testament to Merck’s commitment to bring forward innovative new treatment options for more patients.”

“The approval of a non-surgical treatment option is meaningful for helping patients with certain types of VHL-associated tumors,” said Dr. Ramaprasad Srinivasan, head, Molecular Cancer Therapeutics Section, Urologic Oncology Branch, National Cancer Institute (NCI), and principal investigator on the Cooperative Research and Development Agreement (CRADA) under which the NCI served as a site in Study 004. “In Study 004, nearly half of all patients with VHL-associated renal cell carcinoma, as well as the majority of patients with VHL-associated central nervous system hemangioblastomas or pancreatic neuroendocrine tumors, who were treated with Welireg experienced a reduction of their respective tumor size. The FDA’s approval of Welireg marks an important step forward by introducing a systemic therapy that has the potential to improve the current treatment paradigm for patients with certain types of VHL-associated tumors.”

More                                                                                                                 https://en.wikipedia.org/wiki/Belzutifan

FDA Approves Voxzogo (vosoritide) to Increase Linear Growth in Children with Achondroplasia

 

BioMarin Pharmaceutical Inc. (NASDAQ: BMRN)  announced  the U.S. Food and Drug Administration (FDA)  approval of VOXZOGO™ (vosoritide) for Injection, indicated to increase linear growth in pediatric patients with achondroplasia five years of age and older with open epiphyses (growth plates). This indication is approved under accelerated approval based on an improvement in annualized growth velocity (AGV). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory studies. To fulfill this post-marketing requirement, BioMarin intends to use the ongoing open-label extension studies compared to available natural history.

Voxzogo is the first FDA approved treatment for children with achondroplasia. In patients with achondroplasia, endochondral bone growth, an essential process by which bone tissue is created, is negatively regulated due to a gain of function mutation in fibroblast growth factor receptor 3 gene (FGFR3). Voxzogo, a C-type natriuretic peptide (CNP) analog, represents a new class of therapy, which acts as a positive regulator of the signaling pathway downstream of FGFR3 to promote endochondral bone growth.

"Voxzogo is a medical first that is rooted in BioMarin's focus on molecular genetics and targets the underlying cause of the condition. More than a decade of scientific research underpins the medical advance that Voxzogo represents. We thank the FDA for recognizing its value as the first therapeutic treatment option for children with achondroplasia," said Jean-Jacques Bienaimé, Chairman and Chief Executive Officer of BioMarin. "We extend our gratitude to the community, clinical investigators and the children and their families, who participated and continue to participate in our comprehensive clinical research program as we continue to investigate the full potential of vosoritide."

"Achondroplasia is a lifelong genetic condition resulting from the disordered skeletal architecture caused by impaired endochondral bone growth throughout childhood," said Lynda Polgreen, M.D., an investigator in clinical trials for Voxzogo and an Investigator at The Lundquist Institute at Harbor-UCLA Associate Professor at David Geffen School of Medicine – UCLA. "This approval is an important milestone representing the first time that physicians will be able to offer a therapy targeted at the root cause of the condition for families of children with achondroplasia aged five and older."

"We applaud the FDA for recognizing the urgent unmet medical need for this progressive condition. As a parent of a child with achondroplasia, I see the availability of treatments that impact bone growth as an important step forward," said Amer Haider Co-Founder of Growing Stronger, an organization with a mission to improve the quality of medical care for little people through supporting research. The organization raises nonprofit donations that are granted to researchers focused on dwarfism.

Mr. Haider added, "BioMarin continues to support the achondroplasia community and has a long track record of advancing the standard of care in rare genetic conditions."

With this approval, the FDA also issued a Rare Pediatric Disease Priority Review Voucher (PRV), which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. The rare pediatric disease PRV program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases.

The approval was based on the outcomes of a global randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of Voxzogo and the open-label extension of this Phase 3 study. The study enrolled 121 children aged 5 to 14.9 with achondroplasia. Baseline mean AGV in the placebo and Voxzogo groups was 4.06 cm/year and 4.26 cm/year, respectively. At week 52, the change from baseline in AGV was -0.17 cm/year for the placebo treated patients and 1.40 cm/year for the Voxzogo treated patients, resulting in a statistically significant improvement in AGV of 1.57 cm/year in favor of Voxzogo. After the 52 week double blind, placebo–controlled, phase 3 study, 58 subjects initially randomized to Voxzogo enrolled into an open–label extension. Among the subjects who had two years of follow–up since randomization, the improvement in AGV was maintained.

More...

FDA Approves Seglentis (celecoxib and tramadol hydrochloride) for the Management of Acute Pain

In continuation of my update on celecoxib and tramadol

The U.S. Food and Drug Administration (FDA) has approved Seglentis (celecoxib and tramadol hydrochloride), a proprietary product developed by Esteve Pharmaceuticals' R&D team. It is an innovative first-in-class product comprised of a co-crystal form of celecoxib (an anti-inflammatory) and tramadol (an analgesic) for the treatment of acute pain in adults. This is Esteve's first proprietary research product to enter the United States market.

In words of Dr. Carlos Plata-Salamán, Chief Scientific Officer and Chief Medical Officer of Esteve "This innovation is the result of applying a crystallization technology to improve the physicochemical properties and pharmacokinetic characteristics of its active pharmaceutical ingredients.1,2,4,7,9 The FDA approval means that clinicians and adult patients in the U.S. now have a new treatment option for acute pain management."

Seglentis is the trade name for tablets that contain a co-crystal7 composed of celecoxib and tramadol hydrochloride. It is a new analgesic designed for acute pain management in a multimodal treatment approach3,5,6 targeting four complementary pain relief mechanisms.5,6 It offers a new treatment option for acute pain management aligned with the multimodal analgesia now considered standard of care. 

The novel co-crystal structure produces a unique pharmacokinetic profile of its active pharmaceutical ingredients compared to their individual or combined administration.1,2,4,9 The New Drug Application (NDA) was approved by the U.S. FDA on October 15, 2021.

Staffan Schüberg, Chief Executive Officer of Esteve, said: "We are proud of this milestone as we understand it as a recognition of our daily efforts to meet patient’s needs and to address the challenges the pain community is facing nowadays".

FDA Approves Zimhi (naloxone hydrochloride) Injection for the Treatment of Opioid Overdose

In continuation of my update on naloxone hydrochloride, Adamis Pharmaceuticals Corporation (Nasdaq: ADMP) announced   the U.S. Food and Drug Administration (FDA)   approval of  Adamis’ Zimhi™ (naloxone HCL Injection, USP) 5 mg/0.5 mL product. Zimhi is a high-dose naloxone injection product FDA-approved for use in the treatment of opioid overdose.

Naloxone is an opioid antagonist and is generally considered the drug of choice for immediate administration for opioid overdose. It works by blocking or reversing the effects of the opioid, including extreme drowsiness, slowed breathing, or loss of consciousness. Common opioids include morphine, heroin, tramadol, oxycodone, hydrocodone and fentanyl.

According to statistics published by the Centers for Disease Control and Prevention (CDC), drug overdoses resulted in approximately 96,779 deaths in the United States during the 12-month period ending March 2021, which was a 29% increase over the prior 12-month period. Drug overdoses are now the leading cause of death for Americans under age 50, with more powerful synthetic opioids, like fentanyl and its analogues, responsible for the largest number of those deaths.

Dr. Jeffrey Galinkin, an anesthesiologist, and former member of the FDA Advisory Committee for Anesthetics, Analgesics and Addiction Products, commented, “I am pleased to see this much needed high dose naloxone product will become part of the treatment tool kit as a countermeasure to the continued surge in fentanyl related deaths. The higher intramuscular doses of naloxone in Zimhi should result in more rapid and higher levels of naloxone in the systemic circulation, which in turn, should result in more successful resuscitations.”

Dr. Dennis J. Carlo, President and CEO of Adamis, stated, “We are very excited by this approval and are working with our commercial partner, US WorldMeds, to make this much-needed, lifesaving product readily available to the market. Zimhi provides the highest systemic levels of naloxone compared to any of the nasal or intramuscular products currently available.”

P. Breckinridge Jones, Sr., CEO of US WorldMeds, added, “We are pleased with the approval and now look forward to commercially marketing Zimhi in the United States. US WorldMeds has a proven track-record of successfully commercializing pharmaceutical products and have a First-in-Class and only FDA-approved product, LUCEMYRA® (lofexidine), for the treatment of withdrawal symptoms associated with abrupt opioid discontinuation. We are confident we can leverage our existing commercial infrastructure and presence in the opioid dependence market to speed the uptake of Zimhi and combat the growing opioid crisis. We are preparing for the full commercial launch of ZIMHI which is planned for the first quarter of 2022.”\

FDA Approves Klisyri (tirbanibulin) for the Treatment of Actinic Keratosis on the Face or Scalp

Athenex, Inc., (NASDAQ: ATNX), a global biopharmaceutical company dedicated to the discovery, development, and commercialization of novel therapies for the treatment of cancer and related conditions,   announced  the U.S. Food and Drug Administration (FDA)   approval of Klisyri (tirbanibulin) for the topical treatment of actinic keratosis (AK) on the face or scalp. Klisyri is the first FDA approved branded proprietary product for Athenex and will be launched in partnership with Almirall in the U.S. during the first quarter of 2021. Klisyri will be manufactured by Athenex, highlighting the vertically integrated capabilities of the company ranging from a preclinical lead to a developed product for market launch.

“The FDA approval of Klisyri is a significant milestone for Athenex. Klisyri is a home-grown product discovered and characterized by Athenex scientists and developed from pre-IND to NDA by the Athenex team. We are extremely proud of our team’s excellent execution,” said Dr. Johnson Lau, Chairman and Chief Executive Officer of Athenex. “Approval demonstrates our ability to execute upon the entirety of the drug development and registration process. We are excited to partner with Almirall to bring this first-in-class microtubule inhibitor to patients with actinic keratosis in the US.”

Dr. Rudolf Kwan, Chief Medical Officer of Athenex added, “The FDA approval of tirbanibulin ointment represents a first-in-class microtubule inhibitor for the treatment of actinic keratosis. We believe this small molecule platform has the potential beyond actinic keratosis and are leveraging the platform to develop therapies for other oncology indications.”

Mr. Peter Guenter, CEO of Almirall, stated, “We are delighted to partner with Athenex to market Klisyri in the U.S. and in Europe. This approval from the FDA represents a new option for Dermatologists and marks an important further step for Actinic Keratosis patients. What makes this new therapy particularly exciting is the 5-day course of treatment and its good tolerability. We look forward to the launch of Klisyri in the US in the first quarter of 2021.”

The FDA approved Klisyri based on the data from two pivotal, randomized, double-blind, vehicle-controlled Phase III studies (KX01-AK-003 and KX01-AK-004) that evaluated the efficacy and safety of Klisyri (tirbanibulin) ointment 1% in 702 adults with actinic keratosis of the face or scalp. Tirbanibulin demonstrated complete clearance of actinic keratosis lesions at day 57 in treated face or scalp areas in a significantly higher number of patients compared to vehicle. The most common adverse events were application site pruritus and pain reported by 9% and 10% of treated patients, respectively.

Actinic keratosis is a pre-cancerous skin lesion and is the second most common diagnosis made by dermatologists in the United States. If left untreated, 10-15% of AK lesions will develop into skin cancers.

Athenex has partnered with Almirall (Almirall, S.A., BME: ALM) to market Klisyri for the treatment of actinic keratosis on the face or scalp in the US and EU (including Russia) markets. In addition to the partnership with Almirall, Athenex has partnered with PharmaEssentia (6446.TWO) for actinic keratosis in Taiwan and has partnered with Xiangxue Pharmaceuticals (SHE:300147) for actinic keratosis in China, Hong Kong, and Macau.

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

FDA Approves Klisyri (tirbanibulin) for the Treatment of Actinic Keratosis on the Face or Scalp

FDA Approves Orgovyx (relugolix) as the First Oral Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist for Advanced Prostate Cancer

Myovant Sciences (NYSE: MYOV), a healthcare company focused on redefining care for women and for men, today announced that the U.S. Food and Drug Administration (FDA) has approved Orgovyx (relugolix) for the treatment of adult patients with advanced prostate cancer. Orgovyx, which was granted Priority Review by the FDA, is the first and only oral gonadotropin-releasing hormone (GnRH) receptor antagonist for men with advanced prostate cancer. The approval is based on efficacy and safety data from the Phase 3 HERO study of Orgovyx in men with advanced prostate cancer. Orgovyx is expected to be available in January 2021.

“I am enormously pleased by the approval of Orgovyx and believe it has the potential to usher in a new standard of care for men with prostate cancer requiring androgen deprivation therapy,” said Neal Shore, M.D., medical director of the Carolina Urologic Research Center and HERO program steering committee member. “For the first time, we now have a once-daily oral treatment that effectively and rapidly suppresses testosterone, with a safety analysis showing a lower incidence of major adverse cardiovascular events compared to leuprolide injections, the current standard of care, as evaluated in the Phase 3 HERO study. The COVID-19 pandemic has heightened the importance of oral treatments as men with prostate cancer continue to experience difficulties and risks traveling to receive injections.”

“Prostate cancer is a very personal journey, but a universal truth is that those of us living with this disease want better treatments and options. That is why the approval of Orgovyx is such an exciting milestone that brings a long-awaited oral treatment option to men with advanced prostate cancer,” said Thomas Farrington, president and founder of the Prostate Health Education Network. “It is so important for men to speak with their doctor and explore what treatment is right for them as they focus on their overall health.”

“With the approval of Orgovyx, men with advanced prostate cancer now have a new oral treatment option that has demonstrated robust efficacy and safety, all with one pill taken once-a-day,” said Lynn Seely, M.D., chief executive officer of Myovant Sciences, Inc. “We have successfully built our commercial capabilities to bring this newly approved treatment to the urologists and oncologists who care for men with advanced prostate cancer, with the goal of establishing Orgovyx as the new standard of care. We are incredibly grateful to the men and investigators who participated in the HERO study and to the FDA for expediting the review and approval of Orgovyx through its Priority Review pathway.”

In the Phase 3 HERO study, Orgovyx met the primary endpoint and achieved sustained testosterone suppression to castrate levels (< 50 ng/dL) through 48 weeks in 96.7% (95% confidence interval [CI]: 94.9-97.9) of men, compared with 88.8% (95% CI: 84.6-91.8) of men receiving leuprolide acetate injections, the current standard of care. Orgovyx also achieved several key secondary endpoints compared to leuprolide acetate, including suppression of testosterone to castrate levels at Day 4 and Day 15 (56% versus 0% and 99% versus 12%, respectively) and profound suppression of testosterone (< 20 ng/dL) at Day 15 (78% versus 1%). Orgovyx lowered prostate-specific antigen (PSA), on average, by 65% at Day 15 and by 83% at Day 29. In a substudy, 55% of men treated with Orgovyx achieved normal testosterone levels (> 280 ng/dL) or returned to baseline within 90 days of treatment discontinuation. The most frequent adverse events reported in at least 10% of men in the Orgovyx group were hot flush, musculoskeletal pain, fatigue, constipation, and mild to moderate diarrhea. The HERO data were previously presented in an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, with simultaneous publication in the New England Journal of Medicine.

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

FDA Approves Orgovyx (relugolix) as the First Oral Gonadotropin-Releasing Hormone (GnRH) Receptor Antagonist for Advanced Prostate Cancer

FDA Approves Zokinvy (lonafarnib) for Hutchinson-Gilford Progeria Syndrome and Processing-Deficient Progeroid Laminopathies

Eiger BioPharmaceuticals, Inc. (Nasdaq:EIGR), focused on the development and commercialization of targeted therapies for serious rare and ultra-rare diseases, announced  the U.S. Food and Drug Administration (FDA)  approval of  Zokinvy (lonafarnib) for the treatment of Hutchinson-Gilford Progeria Syndrome (HGPS or Progeria) and processing-deficient Progeroid Laminopathies (PL).  

Progeria and Progeroid Laminopathies are separate and distinct ultra-rare, genetic, premature aging diseases that accelerate mortality in young patients.  Disease manifestations include growth failure, loss of body fat and hair, aged-looking skin, stiffness of joints, hip dislocation, generalized atherosclerosis, cardiovascular disease and stroke.  Untreated children with Progeria die of heart disease at an average age of 14.5 years.  There are 20 children and young adults with Progeria and PL identified and followed in the U.S.  

Zokinvy is a disease-modifying agent that has demonstrated a statistically significant survival benefit in children and young adults with Progeria.  In patients with Progeria, Zokinvy reduced the incidence of mortality by 60% (p=0.0064) and increased average survival time by 2.5 years.  The most commonly reported adverse reactions were gastrointestinal (vomiting, diarrhea, nausea), and most were mild or moderate (Grade 1 or 2) in severity.  Many Progeria patients have received continuous Zokinvy therapy for more than 10 years.

The increase in survival observed with Zokinvy was derived from two open-label clinical trials (N=62) conducted at Boston Children's Hospital.  The survival analysis compared Zokinvy-treated versus Zokinvy-naïve subjects with Progeria born in or after 1991, by age, gender, and geographic location. Zokinvy-naïve patients originated from a separate natural history study (n=81) conducted by The Progeria Research Foundation.

With this approval, the FDA issued a Rare Pediatric Disease Priority Review Voucher (PRV) to Eiger.  The Rare Pediatric Disease Priority Review Voucher program is designed to encourage development of new drugs and biologics for the prevention or treatment of rare pediatric diseases.  Eiger plans to sell the PRV and under the terms of the Collaboration and Supply Agreement with the Progeria Research Foundation (PRF) will share the proceeds equally with PRF.

"The FDA approval of Zokinvy is the result of a pioneering partnership between Eiger BioPharmaceuticals and PRF to bring the first approved therapy to children, young adults and families living with this devastating disease," said David Cory, President and CEO of Eiger.  "We are very proud that the first drug approval at Eiger confers a survival benefit to patients with one of the most ultra-rare, and ultimately fatal, pediatric diseases.  We are extremely grateful to all the children, young adults and their families who have made this possible through participation in the Zokinvy clinical trials."

"The approval of this breakthrough therapy is a critical milestone for the Progeria community and also for Eiger," said Thomas Dietz, PhD, Chairman of the Board at Eiger.  "The Eiger Board congratulates and commends the management team for their incredible dedication leading the company through its first NDA filing and approval, a major accomplishment for Eiger."

PRF Medical Director, Leslie Gordon, MD, PhD, added, "Shortly after our son, Sam, was diagnosed with Progeria, my family and I founded The Progeria Research Foundation to find the cause, treatments, and cure for all children with this fatal disease.  This first approved medication is a truly incredible milestone for the Progeria community as we forge ahead toward finding the cure.  We are thrilled to have Eiger as a partner in bringing Zokinvy to the approval finish line, and for their commitment to ensuring patient access to Zokinvy moving forward."

In support of the patient and healthcare provider community, Eiger is launching our dedicated service center, Eiger OneCare™.  This specialized team will offer personalized support, financial assistance, and access to Zokinvy, all designed for Progeria and processing-deficient Progeroid Laminopathy patients.  Eiger OneCare™ will be available Monday through Friday from 9 AM to 5 PM Eastern Time at 1-833-MYEIGER (1-833-693-4437).

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

FDA Approves Zokinvy (lonafarnib) for Hutchinson-Gilford Progeria Syndrome and Processing-Deficient Progeroid Laminopathies

FDA Approves Eysuvis (loteprednol etabonate) Ophthalmic Suspension for the Short-Term Treatment of the Signs and Symptoms of Dry Eye Disease

Kala Pharmaceuticals, Inc. (NASDAQ:KALA), a biopharmaceutical company focused on the discovery, development and commercialization of innovative therapies for diseases of the eye,  announced   the U.S. Food and Drug Administration (FDA) approval of Eysuvis (loteprednol etabonate ophthalmic suspension) 0.25% for the short-term (up to two weeks) treatment of the signs and symptoms of dry eye disease.

“The FDA approval of Eysuvis as the first prescription therapy specifically developed to address the short-term treatment needs of people living with dry eye disease is a major accomplishment for Kala and an important moment for patients, who have been waiting for an FDA-approved, safe, effective and fast-acting therapy,” said Mark Iwicki, Chairman, President and Chief Executive Officer of Kala Pharmaceuticals. “As we prepare to launch Eysuvis, we will leverage our strong foundation of highly experienced ophthalmology marketing, sales and market access professionals with the goal of establishing Eysuvis as the preferred, first-line prescription therapy for dry eye disease. We’d like to thank the many patients and investigators that were involved in the clinical trials that led to this important milestone.”

Dry eye disease is a chronic, episodic, multifactorial disease affecting the tears and ocular surface, and can involve tear film instability, inflammation, discomfort, visual disturbance and ocular surface damage. Approximately 80 percent of people living with dry eye disease suffer from episodic flares. These flares can be caused by a wide variety of triggers and often cannot be adequately managed with current therapies.

Eysuvis utilizes Kala’s AMPPLIFY® mucus-penetrating particle (MPP) Drug Delivery Technology to enhance penetration of loteprednol etabonate (LE) into target tissue on the ocular surface. LE targets the immune responses that drive acute dry eye disease flares. Prior to Eysuvis, there were no FDA-approved ocular corticosteroids for the treatment of dry eye disease. Kala Pharmaceuticals plans to launch Eysuvis in the U.S. by year-end.

“The approval of Eysuvis ushers in a new era in the treatment of dry eye disease and offers promise to the millions of dry eye patients who experience acute exacerbations, or flares, of their disease each year,” said Edward Holland, M.D., Director of Cornea Services at Cincinnati Eye Institute and Professor of Ophthalmology at the University of Cincinnati. “For the first time we will be able to offer dry eye patients a therapeutic option that provides rapid relief for both the signs and symptoms of the disease and that is safe and well tolerated.”

“Dry eye disease can significantly decrease quality-of-life among affected patients and drive decreased workplace productivity, contact lens intolerance and discontinuation, and poor cataract and refractory surgery outcomes,” said Kelly Nichols, O.D., M.P.H., Ph.D., F.A.A.O., Dean of the University of Alabama at Birmingham School of Optometry. “As the prevalence of dry eye disease increases, there is a tremendous need for new therapies to manage mild-to-moderate dry eye disease patients, many of whom currently go untreated. I am excited by the approval of EYSUVIS and confident that having access to an approved corticosteroid specifically for dry eye disease will meaningfully impact the management of patients across the U.S.”

The FDA granted approval to Eysuvis based on results from four clinical trials, including three Phase 3 trials and one Phase 2 trial, that demonstrated significant improvements in both the signs and symptoms of dry eye disease. Specifically, statistical significance was achieved after two weeks of dosing for the sign endpoint of conjunctival hyperemia in all three Phase 3 trials. Statistical significance was observed in two of the three Phase 3 trials for the symptom endpoints of ocular discomfort severity in both the overall intent-to-treat (ITT) population and in a predefined subgroup of ITT patients with more severe ocular discomfort at baseline. Eysuvis was well-tolerated across the four trials, with adverse events and intraocular pressure increases comparable to that observed with vehicle.

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

FDA Approves Eysuvis (loteprednol etabonate) Ophthalmic Suspension for the Short-Term Treatment of the Signs and Symptoms of Dry Eye Disease

FDA Approves Alkindi Sprinkle (hydrocortisone oral granules) for Pediatric Adrenocortical Insufficiency

In continuation of my update on hydrocortisone 

Eton Pharmaceuticals, Inc (Nasdaq: ETON), a specialty pharmaceutical company focused on developing and commercialising innovative treatments for rare pediatric diseases,  announced the U.S. Food and Drug Administration (FDA)   approval of  Alkindi Sprinkle (hydrocortisone) oral granules as replacement therapy for Adrenocortical Insufficiency (AI) in children under 17 years of age. Alkindi Sprinkle is the first and only FDA-approved granular hydrocortisone formulation for the treatment of adrenocortical insufficiency specifically designed for use in children.

“The FDA approval of Alkindi Sprinkle is a breakthrough for patients and caregivers treating pediatric adrenocortical insufficiency. We are excited to offer an FDA-approved product that enables low dosing and administration of hydrocortisone to pediatric patients,” said Sean Brynjelsen, CEO of Eton Pharmaceuticals. “We look forward to making the product available to patients in the coming months.”

“For years, we heard from parents about their struggle to provide the right dose to their child,” said Dina M. Matos, Executive Director of the CARES Foundation. “We are thrilled the FDA has approved Alkindi Sprinkle for pediatric patients with Adrenocortical Insufficiency including patients with Congenital Adrenal Hyperplasia, a type of Adrenocortical Insufficiency.”

The FDA approval of Alkindi Sprinkle was supported by six clinical studies, including the first and only interventional Phase III study of oral hydrocortisone for Pediatric AI in neonates to children under eight years of age. Prior to the approval of Alkindi Sprinkle, oral hydrocortisone was only FDA-approved in tablet formulations of 5mg and stronger. Many pediatric patients require significantly lower doses and the flexibility of precision titration. Alkindi Sprinkle will be available in 0.5mg, 1mg, 2mg, and 5mg strengths, allowing clinicians greater flexibility to individualize dosing based on each patient’s needs in accordance with the instructions for dosage and administration.

Eton expects Alkindi Sprinkle to be commercially available in the fourth quarter of 2020.

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

FDA Approves Alkindi Sprinkle (hydrocortisone oral granules) for Pediatric Adrenocortical Insufficiency

FDA Approves Gavreto (pralsetinib) for the Treatment of Adults With Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY),  announced  the U.S. Food and Drug Administration (FDA) approval of Gavreto (pralsetinib) for the treatment of adults with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test. This indication was approved under the FDA’s accelerated approval program based on data from the Phase I/II ARROW study. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Gavreto is a once-daily, oral precision therapy designed to selectively target RET alterations, including fusions and mutations.

“The FDA approval of Gavreto for RET fusion-positive non-small cell lung cancer is an important step towards our goal of providing an effective treatment option for every person diagnosed with lung cancer, no matter how rare or hard-to-treat their type of disease,” said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. “We remain committed to finding personalized treatment options for people with cancer based on specific genomic or molecular alterations, and we look forward to partnering with Blueprint Medicines to further explore the potential of Gavreto across multiple RET-altered tumor types.”

RET-activating fusions and mutations are key disease drivers in many cancer types, including NSCLC and medullary thyroid cancer (MTC), and treatment options that selectively target these genetic alterations are limited. In NSCLC, RET fusions represent approximately 1-2% of patients. Biomarker testing for these fusions is the most effective way to identify people who are eligible for treatment with Gavreto.

The approval is based on the results from the Phase I/II ARROW study, in which Gavreto produced durable clinical responses in people with RET fusion-positive NSCLC with or without prior therapy, and regardless of RET fusion partner or central nervous system involvement. Gavreto demonstrated an overall response rate (ORR) of 57% (95% CI: 46%, 68%) and complete response (CR) rate of 5.7% in the 87 people with NSCLC previously treated with platinum-based chemotherapy, and the median duration of response (DoR) was not reached (95% CI: 15.2 months, not reached). In the 27 people with treatment-naïve NSCLC, the ORR was 70% (95% CI: 50%, 86%) with an 11% CR rate. The most common adverse reactions (≥25%) were fatigue, constipation, musculoskeletal pain and increased blood pressure (hypertension).

Gavreto is now the sixth FDA-approved medicine in Genentech’s portfolio of treatments for lung cancer. The FDA granted Breakthrough Therapy Designation to Gavreto for the treatment of RET fusion-positive NSCLC that has progressed following platinum-based chemotherapy and for RET mutation-positive MTC that requires systemic treatment and for which there are no acceptable alternative treatments.

The FDA has also granted Priority Review to Gavreto for the treatment of people with advanced or metastatic RET-mutant MTC and RET fusion-positive thyroid cancer, and is expected to make a decision on approval by February 28, 2021. This New Drug Application (NDA) was accepted for review under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to explore a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.

For those who qualify, Blueprint Medicines will offer patient assistance programs for people prescribed Gavreto by their doctor through YourBlueprint™ . Please visit www.yourblueprint.com or contact 1-888-BLUPRNT for more information.

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

FDA Approves Gavreto (pralsetinib) for the Treatment of Adults With Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer