Invega Hafyera (paliperidone palmitate) Extended-Release Injectable Suspension for schizophrenia

In continuation of my update on paliperidone palmitate

The Janssen Pharmaceutical Companies of Johnson & Johnson announced the U.S. Food and Drug Administration (FDA)   approval of  long-acting atypical antipsychotic Invega Hafyera (6-month paliperidone palmitate), the first-and-only twice-yearly injectable for the treatment of schizophrenia in adults. Before transitioning to Invega Hafyera, patients must be adequately treated with Invega Sustenna (1-month paliperidone palmitate) for at least four months, or Invega Trinza (3-month paliperidone palmitate) for at least one 3-month injection cycle. 

The FDA approval of Invega Hafyera is based on the results of a 12-month, randomized, double-blind, non-inferiority Phase 3 global study that enrolled 702 adults (ages 18-70) living with schizophrenia from 20 countries. The results showed non-inferiority of Invega Hafyera compared to Invega Trinza on the primary endpoint of time to first relapse at the end of the 12-month period. Results found that 92.5 percent of patients treated with Invega Hafyera and 95 percent treated with Invega Trinza were relapse-free at 12 months.1 Relapse was defined as psychiatric hospitalization, increase in Positive and Negative Syndrome Scale [PANSS] total score, increase in individual PANSS item scores, self-injury, violent behavior, or suicidal/homicidal ideation.

The safety profile observed in the trial was consistent with previous studies of Invega Sustenna and Invega Trinza with no new safety signals emerging.1 The most common adverse reactions (≥5%) in the Invega Hafyera clinical trial were upper respiratory tract infection (12%), injection site reaction (11%), weight increase (9%), headache (7%), and parkinsonism (5%).

“Before I found the right treatment plan for me, my symptoms often got in the way of things that I loved to do,” said Patrick, an adult living with schizophrenia and a participant in the clinical trial. “But since my doctor introduced me to Janssen’s long-acting injectable options and my symptoms are controlled, I have the clarity to focus on the present, but also the stability to plan for my future.”

Schizophrenia is a complex and chronic brain disorder in which the symptoms and potential for relapse (or recurrence of symptoms) can impact many aspects of a person’s daily life. On average, an adult with schizophrenia experiences nine relapses in less than six years, often due to missed doses of medication. Adults living with schizophrenia and their loved ones face ongoing functional, emotional, and financial burdens. In addition, patients who experience more relapses may have more hospitalizations, which can lead to higher medical costs for patients, hospital systems, and payers.

“For too long, we’ve accepted relapse as a normal part of living with schizophrenia, while research continues to demonstrate that stronger medication adherence means better patient outcomes,” said Gustavo Alva*, M.D., DFAPA, Medical Director at ATP Clinical Research and 6-month paliperidone palmitate clinical trial investigator. “The Phase 3 trial results provide compelling evidence that 6-month paliperidone palmitate offers longer-term symptom control with the fewest doses per year, which may support greater patient adherence.”

Recently, the National Council for Mental Wellbeing and the American Psychiatric Association updated their schizophrenia treatment guidance and guidelines to expand the recommended use of long-acting injectables for appropriate adult patients living with schizophrenia.

Invega Hafyera is a long-acting injectable treatment that is administered by a healthcare provider in the upper buttocks area every six months. Invega Hafyera dissolves slowly into the bloodstream after injection, resulting in continuous treatment and symptom control over six months.

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

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.

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FDA Approves Vuity (pilocarpine HCI ophthalmic solution) to Treat Presbyopia (Age-Related Blurry Near Vision)....

Allergan, an AbbVie (NYSE: ABBV) company,   announced the U.S. Food and Drug Administration (FDA) approval of Vuity (pilocarpine HCl ophthalmic solution) 1.25% for the treatment of presbyopia, commonly known as age-related blurry near vision, in adults. Vuity is the first and only FDA-approved eye drop to treat this common and progressive eye condition that affects 128 million Americans, nearly half of the U.S. adult population.

"Most adults cope with presbyopia, or difficulty with near vision, as we age. Beginning around the age of 40, many find themselves using reading glasses, holding text further away, or even increasing the font size and lighting on screens to try to see more clearly," said Michael Severino, M.D., vice chairman and president, AbbVie. "We are proud to offer Vuity as a first-of-its-kind once-daily eye drop that we believe will change the way people and their eye doctors approach presbyopia. The FDA approval of Vuity exemplifies our continued pursuit of innovative new treatments that push the boundaries of what's possible in eye care."

Vuity is a daily, prescription eye drop that works in as early as 15 minutes and lasts up to 6 hours, as measured on day 30, to improve near and intermediate vision without impacting distance vision. Specifically designed for presbyopia, Vuity is an optimized formulation of pilocarpine, an established eye care therapeutic, delivered with pHast™ technology. The proprietary pHast™ technology allows Vuity to rapidly adjust to the physiologic pH of the tear film. Vuity uses the eye's own ability to reduce pupil size, improving near vision without affecting distance vision.

"As we age, the lenses of our eyes become less flexible, making it more difficult to focus on things up close. Vuity offers a novel, safe, well-tolerated and effective alternative to current options for managing age-related blurry near vision," said George O. Waring IV, M.D., FACS, medical director, Waring Vision Institute, South Carolina, and GEMINI 1 and GEMINI 2 principal study investigator. "I am particularly encouraged by the rapid onset of action and duration of efficacy for Vuity to improve near and intermediate vision without impacting distance vision with one drop daily, particularly for those with mild to moderate presbyopia."  

The FDA approval of Vuity is based on data from two pivotal phase 3 clinical studies, GEMINI 1 and GEMINI 2, which evaluated the efficacy, safety and tolerability of Vuity for the treatment of presbyopia. In both studies, Vuity met the primary endpoint, reaching statistical significance in improvement in near vision in low light (mesopic) conditions without a loss of distance vision versus the vehicle (placebo) on day 30 at hour 3. Additionally, improvement was seen as early as 15 minutes and lasted through 6 hours. There were no serious adverse events observed in participants receiving VUITY in either the GEMINI 1 or GEMINI 2 study. The most common adverse events occurring at a frequency of >5% were headache and eye redness.

Highlights from the Phase 3 GEMINI 1 & GEMINI 2 Clinical Studies

• A total of 750 participants aged 40 to 55 years old with presbyopia were randomized in the two studies in a one-to-one ratio of placebo to Vuity.
• Participants were instructed to administer one drop of Vuity or placebo once daily in each eye.
• Both studies met their primary endpoints with a statistically significant proportion of participants treated with Vuity gaining three lines (the ability to read three additional lines on a reading chart) or more in mesopic (in low light), high contrast, binocular Distance Corrected Near Visual Acuity (DCNVA), without losing more than 1 line (5 letters) of Corrected Distance Visual Acuity (CDVA) at day 30, hour 3, versus placebo.
• There were no serious adverse events observed in any participants treated with Vuity in either clinical study. The most common treatment emergent non-serious adverse events occurring at a frequency of >5% in participants treated with Vuity were headache and eye redness.

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.”\