Monday, January 23, 2023

FDA Approves Iyuzeh (latanoprost ophthalmic solution) for the Reduction of Elevated Intraocular Pressure (IOP) in Patients with Open-Angle Glaucoma or Ocular Hypertension

In continuation of my update on Latanoprost

Thea Pharma, Inc. (“Thea”), the U.S. subsidiary of Europe’s leading independent pharmaceutical company, Laboratoires Théa, dedicated to the research, development and commercialization of ophthalmic products,  announced U.S. Food and Drug Administration (FDA) approval of  the New Drug Application (NDA) of Iyuzeh™ (latanoprost ophthalmic solution) 0.005% for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

Iyuzeh™ is the first and only clinically proven formulation of latanoprost available in the United States that is preservative-free. Iyuzeh™ is formulated without any of the preservatives commonly used in topical ocular preparations, including benzalkonium chloride (BAK). Iyuzeh™ has demonstrated consistent IOP-lowering effects and proven tolerability across multiple trials in the U.S. and Europe. In randomized, controlled clinical trials of patients with OAG or OHT with mean baseline IOP of 19-24 mmHg, Iyuzeh™ lowered IOP by 3 – 8 mmHg versus 4 – 8 mmHg by XALATAN® (latanoprost ophthalmic solution) 0.005%, which is preserved with BAK.

“The approval of Iyuzeh™ is a significant milestone for Théa Group, as this is our first FDA approval for a prescription ophthalmic medicine, for our U.S. subsidiary,” said Jean-Frédéric Chibret, President of the Théa Group. “Marketed outside of the U.S. as Monoprost®, the market leading prostaglandin analogue (PGA) in volume, is available in over 46 countries around the world, including France, Germany, Spain, United Kingdom, Italy, and Canada. We are extremely proud to bring our unique preservative-free latanoprost eye drop, Iyuzeh™ to the U.S.

“Our novel patent protected formulation has been made possible by Théa’s innovative scientists. They were able to solve the challenges of solubilizing and stabilizing latanoprost such that Iyuzeh does not need to be manufactured, distributed, or stored at refrigerated temperatures unlike some other competitive brand and generic latanoprost and PGA products. Additionally, Théa is responding to an important unmet need across all stakeholders in the treatment of OAG and OHT. Many patients on preserved glaucoma medications experience moderate to severe signs and symptoms of ocular surface disease (OSD) that can cause discomfort for patients, frustration for physicians, and drive additional costs for payers,” said Susan Benton, Thea’s U.S. President. “We look forward to introducing Iyuzeh™ to U.S. eyecare practitioners in the second half of 2023.”

About Iyuzeh™

Iyuzeh™ (latanoprost ophthalmic solution) 0.005%, an opalescent, white to slightly yellow ophthalmic solution, is a topical formulation of latanoprost that is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Iyuzeh™ does not contain a preservative – it is the first and only preservative-free formulation of latanoprost, the most prescribed prostaglandin F2α analogue (PGA) in the United States. The recommended dosage of Iyuzeh™ is one drop in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal. Reduction of the IOP starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours. IOP reduction is present for at least 24 hours.

In the two clinical trials conducted with Iyuzeh™ (latanoprost ophthalmic solution) 0.005%, the most frequently reported ocular adverse reactions were conjunctival hyperemia (34%) and eye irritation (19%) compared to XALATAN, the preserved 0.005% latanoprost reference product which reported conjunctival hyperemia (37%) and eye irritation (31%).

Friday, January 20, 2023

FDA Approves Rezlidhia (olutasidenib) for Relapsed or Refractory Acute Myeloid Leukemia with a Susceptible IDH1 Mutation

Rigel Pharmaceuticals, Inc. announced the U.S. Food and Drug Administration (FDA)  approval  of  Rezlidhia (olutasidenib) capsules for the treatment of adult patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test. Rezlidhia is an oral, small molecule, inhibitor of mutated IDH1 designed to bind to and inhibit mIDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation of myeloid cells.

"Rezlidhia is a novel, non-intensive monotherapy treatment in the relapsed/refractory AML setting demonstrating a CR+CRh rate of 35% in patients with over 90% of those responders in complete remission. The 25.9 months median duration of CR+CRh is a clinically meaningful improvement for AML patients and appears to be longer than currently available treatment options," said Jorge E. Cortes, M.D., Director, Georgia Cancer Center, Cecil F. Whitaker Jr., GRA Eminent Scholar Chair in Cancer, and Phase 2 trial investigator. "Given the limited treatment options for adult patients with mIDH1 R/R AML, who typically have a poor prognosis, Rezlidhia may provide an effective, new treatment option with a well characterized safety profile."

The FDA approval was supported by data from the open-label Phase 2 registrational study evaluating Rezlidhia monotherapy at a dose of 150 mg twice daily in 153 mIDH1 R/R AML patients. The efficacy-evaluable population was 147 patients who initiated Rezlidhia at least six months prior to the interim analysis cutoff date of June 18, 2021, and who had a centrally confirmed IDH1 mutation. The primary endpoint was a composite of a complete remission (CR) plus a complete remission with partial hematological recovery (CRh). CRh is defined as less than 5% blasts in the bone marrow, no evidence of disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil count >500/microliter).

Results from the trial demonstrated a 35% (51/147) CR+CRh rate in mIDH1 R/R AML patients, with a median duration of response of 25.9 months. The median time to CR or CRh was 1.9 months. Of the patients who achieved the primary endpoint of CR+CRh, 92% (47/51) were CR with a median duration of response of 28.1 months. Rezlidhia was well tolerated in the study with an adverse event profile largely characteristic of symptoms or conditions experienced by patients with AML undergoing treatment. Differentiation syndrome was observed in 16% of patients and was manageable in most cases with dose interruption and corticosteroids. Hepatotoxicity, presenting as increases in liver function parameters, occurred in 23% of patients and most cases were manageable with dose modifications.

"We are delighted by the approval of Rezlidhia based on the strength of data supporting the efficacy and safety of the product," said Raul Rodriguez, Rigel's president and CEO. "Rezlidhia provides a new and important, oral therapy option for patients who typically have a poor clinical outcome. Additionally, this approval greatly strengthens and expands Rigel's commercial hematology-oncology portfolio. I would like to extend our sincerest thanks to all the patients, their families and caregivers, the doctors, the FDA, and our team members who have all contributed to the approval of Rezlidhia."

In August 2022, Rigel and Forma Therapeutics, Inc. announced they entered an exclusive, worldwide license agreement to develop, manufacture and commercialize Rezlidhia. Under the terms of the agreement, Rigel will be responsible for the launch and commercialization of Rezlidhia in the U.S., and intends to work with potential partners to further develop and commercialize the product outside the U.S.

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Thursday, January 19, 2023

FDA Approves Krazati (adagrasib) for Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with a KRASG12C Mutation

Mirati Therapeutics, Inc. (NASDAQ: MRTX), a targeted oncology company, announced the U.S. Food and Drug Administration (FDA)  approval of Krazati™ (adagrasib), a targeted treatment option for adult patients with KRASG12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy.

This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of a clinical benefit in a confirmatory trial(s).

"The FDA approval of Krazati is a positive development for thousands of patients with KRASG12C mutations, including the approximately 14% of patients with NSCLC adenocarcinomas histology that harbor a KRASG12C mutation.1 Mirati is thrilled to make Krazati available in a tablet formulation to patients in the U.S. with advanced NSCLC who have progressed beyond a first-line treatment for the historically difficult-to-treat KRAS mutation," David Meek, chief executive officer, Mirati Therapeutics, Inc., continued, "We look forward to continuing to advance our Krazati development program including several monotherapy and combination studies in KRASG12C-mutated solid tumors."

Krazati has demonstrated a positive benefit-risk profile with accelerated approval based on the Phase 2 registration-enabling cohort of the KRYSTAL-1 study, evaluating Krazati 600 mg capsules administered orally twice daily in 116 patients with KRASG12C-mutated advanced NSCLC who previously received treatment with a platinum-based regimen and an immune checkpoint inhibitor. The primary efficacy endpoints were confirmed ORR and DOR as evaluated by blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST v1.1).

The trial demonstrated an ORR of 43% (95% CI: 34-53) with 80% (95% CI: 71-87) of patients achieving disease control. The median DOR was 8.5 months (95% CI: 6.2-13.8).

In a pooled efficacy analysis (n=132) including Phase 1/1b NSCLC and registrational Phase 2 NSCLC cohorts from the KRYSTAL-1 study evaluating adagrasib as a single agent at 600 mg capsules orally twice daily, adagrasib showed an ORR of 44% and a disease control rate of 81% based on BICR, a median DOR of 12.5 months (95% CI, 7.3-NE) and median overall survival of 14.1 months (94% CI, 9.2-19.2).

The safety profile of Krazati was evaluated in a pooled patient population with NSCLC and other solid tumors as a single agent at 600 mg orally twice daily in 366 patients enrolled in KRYSTAL-1 and KRYSTAL-12. The most common (≥ 25%) adverse reactions were nausea, diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal impairment, edema, dyspnea and decreased appetite. Permanent discontinuation of Krazati due to an adverse reaction occurred in 13% of patients.

Although KRASG12C is the most common KRAS mutation in NSCLC, patients have had limited options for the treatment of this debilitating and difficult-to-treat condition.2,3

"The approval of Krazati offers an effective therapy for patients with advanced NSCLC harboring the KRASG12C mutation. The positive ORR and DOR results, as observed in previously treated patients with NSCLC harboring the KRASG12C mutation, demonstrate the effectiveness of Krazati as an option for these difficult-to-treat patients," said Shirish M. Gadgeel, MD, chief of the Division of Hematology and Oncology, Department of Internal Medicine, Henry Ford Cancer Institute/Henry Ford Health System.

"KRASG12C in NSCLC is an area of high unmet need and new treatment options offer patients and our community new hope for survivorship," said Bonnie J. Addario, co-founder and board chair of the GO2 Foundation for Lung Cancer. "I'm pleased that patients have options, there's more awareness of this disease and we are all focused on improving the journeys of people living with KRASG12C-mutated NSCLC."

The Company partnered with Agilent and QIAGEN to develop blood- and tissue-based companion diagnostics (CDx), respectively, for Krazati that are now available. With tissue and blood modalities for companion diagnostics, patients have more flexibility, and clinicians have greater options for biomarker testing. These solutions help to personalize a patient's treatment path.

Mirati Therapeutics is launching Mirati & Me, a comprehensive program dedicated to supporting patients, caregivers and the oncology community including coverage and access, financial, educational and emotional support services. 

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Wednesday, January 18, 2023

FDA Approves Olpruva (sodium phenylbutyrate) for Patients with Urea Cycle Disorders

In continuation of my update on Phenyl butyrate 

Acer Therapeutics Inc. and its collaboration partner, RELIEF THERAPEUTICS Holding SA (“Relief”),  announced the U.S. Food and Drug Administration (FDA)  approval Olpruva™ (sodium phenylbutyrate) of  oral suspension in the U.S. for the treatment of certain patients living with urea cycle disorders (UCDs) involving deficiencies of carbamylphosphate synthetase (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase (AS).

“The FDA’s approval of Olpruva, an innovative formulation of sodium phenylbutyrate packaged for the first time in single-dose envelopes, marks the culmination of our ongoing dedication to develop new and differentiated treatment options for those affected by rare diseases,” said Chris Schelling, chief executive officer and founder of Acer. “Patients who are living with UCDs now have an alternative treatment option with Olpruva™, to address some of the challenges they may have with existing therapy. We are pleased to be able to provide a new, approved treatment choice for those living with this challenging disease.”

Mr. Schelling continued, “This approval represents the first FDA-approved product for Acer, validating our ability to identify and develop treatments where science can be applied in novel ways and make them available to patients as quickly and efficiently as possible. In addition, this approval unlocks our Marathon debt funding option and provides us with resources to advance our pipeline of investigational product candidates.”

“The daily challenges of living with a UCD can be overwhelming and emotionally draining for patients and their families,” said Tresa Warner, president of the National Urea Cycle Disorders Foundation. “We welcome new treatment options that can help patients, caregivers and their healthcare teams manage UCDs.”

Olpruva’s™ approval triggers the availability of a $42.5 million term loan to Acer under the previously announced March 2022 loan agreement the Company entered into with affiliates of Marathon Asset Management L.P. If Acer requests and receives the loan proceeds, management believes it will have sufficient resources to fund current operations into H2 2023.

Olpruva™ has been approved as an oral suspension by the FDA for the treatment of patients with UCDs. UCDs are a group of rare, genetic disorders that can cause harmful ammonia to build up in the blood, potentially resulting in brain damage and neurocognitive impairments, if ammonia levels are not controlled.1 Any increase in ammonia over time is serious. Therefore, it is important to adhere to any dietary protein restrictions and have alternative medication options to help control ammonia levels.

“This FDA approval is a significant milestone for patients with UCDs in the U.S., offering an additional choice to manage their condition,” added Jack Weinstein, chief executive officer of Relief. “We look forward to building on Olpruva™’s approval in the U.S. and expanding its availability into other territories outside of the U.S.”

Olpruva™ received FDA approval under section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (FDCA), a regulatory pathway that allows applicants to rely, at least in part, on third party data for approval. In its New Drug Application (NDA), Acer cited preclinical and clinical safety and efficacy data from the reference listed drug (RLD), BUPHENYL® powder, which is approved as adjunctive therapy in the chronic management of patients with UCDs involving deficiencies of CPS, OTC or AS. In its NDA, Acer also provided additional data including studies that evaluated the bioavailability and bioequivalence of Olpruva™ compared to BUPHENYL® powder. The data from these studies, presented at the Society for Inherited Metabolic Disorders (SIMD) Annual Meeting in April 2022 and the Genetic Metabolic Dieticians International (GMDI) Conference in May 2022, showed that Olpruva™ was bioequivalent to BUPHENYL® powder.

Commitment to Patient Access
Acer intends to offer Navigator by Acer Therapeutics, a suite of integrated patient support services designed to facilitate access to therapy. Navigator by Acer Therapeutics is designed to assist UCD patients with support, access, education, and adherence.

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Tuesday, January 17, 2023

FDA Approves Sezaby (phenobarbital sodium powder for injection) for the Treatment of Neonatal Seizures

In continuation of my update on Phenobarbitol 

Sun Pharmaceutical Industries Limited and Sun Pharma Advanced Research Company Ltd.  announced the U.S. Food and Drug Administration (US FDA)  approval of  Sezaby™ (phenobarbital sodium powder for injection) for the treatment of neonatal seizures.

With this approval, Sezaby becomes the first and only product specifically indicated in the U.S. for the treatment of neonatal seizures in term and preterm infants. Sezaby is expected to be available in the U.S. in Q4FY23.

Sezaby is a benzyl alcohol-free and propylene glycol-free formulation of phenobarbital sodium powder for injection. It was granted orphan drug designation by the US FDA for the treatment of neonatal seizures.

Sezaby was recently licensed by SPARC to Sun Pharma. Under the terms of the license agreement, SPARC is eligible to receive a milestone payment on approval of Sezaby by the US FDA.

“Sezaby is an exciting addition to our growing portfolio of specialty branded products in the U.S.,” said Abhay Gandhi, CEO North America, Sun Pharma. “As the first and only product specifically indicated to treat seizures in term and preterm infants, Sezaby has the potential to make a difference in the lives of patients and their families.”

“For years, physicians have had limited treatment options to manage neonates with seizures. SPARC is proud to have developed benzyl alcohol-free and propylene glycol-free phenobarbital sodium powder for injection as the first treatment option now approved by the US FDA,” said Anil Raghavan, CEO, SPARC. Sezaby was approved based on the results of NEOLEV2, a phase 2 study that evaluated levetiracetam compared to phenobarbital in the first-line treatment of neonatal seizures.

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Monday, January 16, 2023

FDA Approves Airsupra (albuterol/budesonide) Metered-Dose Inhaler to Reduce the Risk of Asthma Exacerbations

In continuation of my update on albuterol/budesonide



Airsupra (albuterol/budesonide), formerly known as PT027, has been approved in the US for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in people with asthma aged 18 years and older.

The approval by the Food and Drug Administration (FDA) was based on results from the MANDALA and DENALI Phase III trials. In MANDALA, Airsupra significantly reduced the risk of severe exacerbations compared to albuterol in patients with moderate to severe asthma when used as an as-needed rescue medication in response to symptoms. Importantly, in the secondary endpoint of mean annualised total systemic corticosteroid exposure, Airsupra demonstrated a significant reduction compared to albuterol at the approved dose of 180mcg albuterol/160mcg budesonide. In DENALI, Airsupra significantly improved lung function compared to the individual components albuterol and budesonide in patients with mild to moderate asthma.

Airsupra is a first-in-class, pressurised metered-dose inhaler (pMDI), fixed-dose combination rescue medication containing albuterol, a short-acting beta2-agonist (SABA), and budesonide, an anti-inflammatory inhaled corticosteroid (ICS) in the US. It is being developed by AstraZeneca and Avillion.

Bradley E. Chipps, Past President of the American College of Allergy, Asthma & Immunology and Medical Director of Capital Allergy & Respiratory Disease Center in Sacramento, US, said: “People with asthma are at risk of severe exacerbations regardless of their disease severity or level of control. Current albuterol rescue inhalers alleviate acute symptoms, but do not treat the underlying inflammation in asthma. The approval of Airsupra means that for the first time, adults with asthma in the US have a rescue treatment to manage both their symptoms and the inflammatory nature of their disease.”

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “With patients experiencing more than 10 million asthma exacerbations each year in the US and uncontrolled asthma expected to cost the US economy billions of dollars in direct medical costs alone over the next 20 years, today’s positive decision is good news for those adults with asthma who make up more than 80% of asthma patients in the US. Physicians will be able to offer their patients Airsupra, an important new rescue treatment that reduces the risk of asthma exacerbations.”

Asthma is a chronic, inflammatory respiratory disease with variable symptoms that affects as many as 262 million people worldwide. In the US over 21 million adults have asthma, representing more than 80% of the total number of people with asthma. Adults have 8.5 million exacerbations each year in the US. Uncontrolled asthma will cost the US economy an estimated $300 billion (in 2018 dollar values) in the next 20 years in direct medical costs alone.

The safety and tolerability of Airsupra in both trials were consistent with the known profiles of the components,1,2 with the most common adverse events including headache, oral candidiasis, cough and dysphonia.

Friday, January 13, 2023

FDA Approves Sunlenca (lenacapavir) Twice-Yearly Treatment for People Living With Multi-Drug Resistant HIV

Gilead Sciences, Inc. (Nasdaq: GILD)  announced that Sunlenca® (lenacapavir), in combination with other antiretroviral(s) (ARV), has been granted approval by the U.S. Food and Drug Administration (FDA) for the treatment of HIV-1 infection in heavily treatment-experienced (HTE) adults with multi-drug resistant (MDR) HIV-1 infection. Sunlenca has a multi-stage mechanism of action distinguishable from other currently approved classes of antiviral agents and no known cross resistance exhibited in vitro to other existing drug classes. Sunlenca offers a new, twice-yearly treatment option for adults with HIV that is not adequately controlled by their current treatment regimen.

“An effective antiretroviral regimen can be devised for most people living with the virus; however, some people living with HIV no longer have durable viral suppression due to resistance to multiple classes of antiretroviral therapies,” said Sorana Segal-Maurer, MD, Director of the Dr. James J. Rahal Jr. Division of Infectious Diseases at NewYork-Presbyterian Queens, Professor of Clinical Medicine at Weill Cornell Medicine and the Site Principal Investigator for the CAPELLA trial. “The availability of new classes of antiretroviral drugs is critical for heavily treatment-experienced people with multi-drug resistant HIV. Following today’s decision from the FDA, lenacapavir helps to fill a critical unmet need for people with complex prior treatment histories and offers physicians a long-awaited twice-yearly option for these patients who otherwise have limited therapy choices."

Despite the significant advances in ARV therapy, there remain numerous critical and pressing unmet needs for people living with HIV. This is particularly true for individuals who are heavily treatment experienced – which account for an estimated 2% of adults living with HIV who are on treatment globally –- and are unable to maintain virologic suppression due to resistance, intolerance or safety considerations. This type of complexity further increases the chance of treatment failure, underscoring the need for new treatment options that are active against resistant variants of the virus with a novel mechanism of action.

Lenacapavir is a breakthrough innovation with the potential to be a preferred and versatile foundational long-acting agent due to its therapeutic potency and a range of dosing frequencies and routes of administration. Lenacapavir is being developed as a foundation for Gilead’s future HIV therapies with the goal of offering several long-acting options that help address individual needs and preferences that may help optimize outcomes and reduce burden of care. Lenacapavir is being studied in multiple ongoing early and late-stage development programs and has the potential to offer a diverse set of person-centric options for treatment and prevention that could uniquely fit into the lives of people living with HIV and people who would benefit from pre-exposure prophylaxis (PrEP). The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established.

“This news is an important milestone in the work to help end the HIV epidemic as Sunlenca is now the only FDA-approved twice-yearly treatment for people with multi-drug resistant HIV,” said Daniel O’Day, Chairman and Chief Executive Officer, Gilead Sciences. “Gilead scientists have developed a unique and potent antiretroviral medicine in Sunlenca with the potential for flexible dosing options. Our goal is to deliver multiple long-acting options for treatment and prevention that are tailored to the needs of people living with HIV and people who could benefit from PrEP medicines.”

The FDA approval for Sunlenca is supported by data from the Phase 2/3 CAPELLA trial, which evaluated lenacapavir in combination with an optimized background regimen in people with multi-drug resistant HIV-1 who are heavily treatment experienced. CAPELLA participants had undergone previous treatment with a median of nine antiretroviral medications. In this patient population with significant unmet medical need, 83% (n=30/36) of participants randomly allocated to receive lenacapavir in addition to an optimized background regimen achieved an undetectable viral load (<50 copies/mL) at Week 52. Additionally, these participants achieved a mean increase in CD4 count of 82 cells/µL. These data were presented at the 29th Conference on Retroviruses and Opportunistic Infections (virtual CROI 2022).

Sunlenca was reviewed and approved as a medication with FDA Breakthrough Therapy Designation, which is intended to expedite the development and review of new drugs which may demonstrate substantial improvement over available therapy. In May 2019, the FDA granted Breakthrough Therapy Designation for the development of lenacapavir for the treatment of HIV-1 infection in heavily treatment-experienced patients with multi-drug resistance in combination with other antiretroviral drugs.

Lenacapavir, alone or in combination, is not approved by any regulatory authority outside of the United States, United Kingdom, Canada or the European Union for any use. The European Marketing Authorization applies to all 27 member states of the European Union, as well as Norway, Iceland and Liechtenstein.

The use of lenacapavir for HIV prevention is investigational and the safety and efficacy of lenacapavir for this use have not been established. Gilead is studying the safety and efficacy of lenacapavir for HIV prevention in multiple ongoing clinical studies.

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