Clinical News: January 2024

January 31, 2024

Your monthly source for drug information highlights

Clinical News

Your monthly source for drug information highlights

Hot topics

UPDATED ATOPIC DERMATITIS GUIDELINES

The American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force (AAAAI/ACAAI JTF) published 2023 guidelines (prior version 2012) on atopic dermatitis (AD), also known as eczema. Twenty-five evidence-based recommendations address various potential therapeutic modalities including topical agents, dilute bleach baths, dietary avoidance, allergen immunotherapy, as well as systemic therapies and light therapy. A few of the drug therapy changes in the 2023 guidelines are highlighted.

In patients with uncontrolled AD despite moisturizer use, topical corticosteroids (TCS) or topical calcineurin inhibitors (TCIs) are recommended. Additionally, TCS or TCI are recommended as proactive therapy for patients with relapsing AD. Crisaborole 2% ointment (Eucrisa®), a topical phosphodiesterase-4 (PDE4) inhibitor, is suggested for mild-to-moderate AD refractory to moisturizers. However, topical JAK inhibitors (ruxolitinib [Opzelura®]) are suggested against for mild-to-moderate AD that is refractory to moisturizer monotherapy. The biologics, dupilumab (Dupixent®; patients ≥ 6 months old) and tralokinumab-ldrm (Adbry®; patients ≥ 12 years old), are recommended in the setting of moderate-to-severe AD that is refractory to mid- to high-potency topical treatment, as well as for patients who are intolerant or unable to use a mid- to high-potency topical treatment. Similarly, cyclosporine is suggested to be considered for adolescents and adults with moderate-to-severe AD that is refractory or who have an intolerance/are unable to use mid- to high-potency topical treatment and biologics. Oral JAK inhibitors (abrocitinib [Cibinqo™], baricitinib [Olumiant®], or upadacitinib [Rinvoq®]) are suggested only following a careful analysis of risks and benefits for adults and adolescents with moderate-severe refractory AD or who are intolerant/unable to use mid- to high-potency topical treatment and systemic treatment, including a biologic agent. Systemic corticosteroids, azathioprine, methotrexate, and mycophenolate mofetil are suggested against, and use of baricitinib 1 mg daily is recommended against. The guidelines include patient handouts to aid in education and discussions related to shared decision-making.

FDA AUTHORIZATION OF FLORIDA DRUG IMPORTATION

Florida’s Agency for Health Care Administration’s drug importation program has received authorization from the U.S. FDA, initiating the pathway towards Florida importing certain prescription medications from Canada. Prescription drugs may be eligible for importation if importation will significantly decrease the consumer’s cost without posing any added safety or health risks. The section 804 importation program (SIP) authorized for Florida is effective for two years from the FDA being notified of the first shipment of imported drugs. Prior to drug importation, the Agency for Health Care Administration in Florida is required to (1) submit drug-specific information to the FDA for review/approval; (2) confirm imported drug products have been tested for authenticity and alignment with other FDA specifications/standards; and (3) relabel the drugs to be consistent with FDA-approved labeling. A quarterly report is required to be submitted to the FDA providing an evaluation of drugs that were imported, financial savings, and any safety/quality concerns. Additional requirements for Florida’s Agency include maintaining supply chain integrity, tracking adverse event reports, and adhering to drug recall processes. The drug importation program was authorized under section 804 of the Federal Food, Drug, and Cosmetic Act (FD&C Act).

BIOGEN HALTS DEVELOPMENT OF ADUHELM®

Biogen has announced a realignment of resources in their Alzheimer’s disease (AD) portfolio resulting in discontinuation of the development and commercialization of aducanumab-avwa (Aduhelm). The agent received Accelerated Approval in June 2021; however, the FDA’s decision was controversial and followed an FDA advisory committee vote against approval due to a questionable risk-benefit profile. A requirement of the Accelerated Approval was a confirmatory phase 4 post-marketing trial (ENVISION) that would have been utilized for seeking full traditional approval of aducanumab-avwa. Biogen has stated the decision to withdraw resources for aducanumab-avwa was not the result of any safety or efficacy concerns but allows for a reprioritization to focus on lecanemab-irmb (Leqembi®) as well as potential pipeline products. The sponsor did not identify commercialization partners or external financing to support aducanumab-avwa’s development. Rights to aducanumab-avwa will revert to Neurimmune, and the phase 4 ENVISION study will be terminated. The Centers for Medicare & Medicaid Services (CMS) had previously announced coverage restrictions for the agent.

More trending topics

WEIGHT MANAGEMENT CORNER

The FDA is evaluating three potential safety signals (alopecia, aspiration, suicidal ideation) with glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) based on the FDA’s Adverse Event Reporting System (FAERS) from July to September 2023. The agency has also issued a Drug Safety Communication providing an update on its ongoing evaluation of reports of suicidal thoughts and actions in patients taking GLP-1 RAs. After preliminary review of data from FAERS and clinical trials, evidence has not shown an association between GLP-1 RAs and suicidal thoughts/actions. However, the FDA will perform additional evaluations including a meta-analysis and post-marketing data analysis from the Sentinel System. Patients are instructed not to stop taking GLP-1 RAs without consulting with their HCP. HCPs should monitor patients for new/worsening depression, suicidal thoughts, or unusual mood/behavior changes.

CLINICAL CORNER

The FDA has announced implementation of previously planned labeling updates for all (brand and generic) immediate-release (IR) and extended-release/long-acting (ER/LA) opioid analgesics. These required safety labeling updates were previously communicated in an April 2023 Drug Safety Communication and include the addition of language stating: (1) the risk of overdose increases as the dose increases for opioids; (2) IR opioids should not be used for an extended period of time unless a patient’s pain remains severe enough to necessitate their use and alternative treatments are not adequate; (3) a number of acute pain conditions treated in the outpatient setting do not need more than a few days of an opioid pain medicine; and (4) ER/LA opioids should be reserved for severe and persistent pain requiring an extended treatment duration with a daily opioid and for which alternative therapies are not adequate. Additional label updates include a new warning about opioid-induced hyperalgesia (OIH), in which opioid use leads to an increase in pain (hyperalgesia) or an increased sensitivity to pain (allodynia). Details were also added to aid in differentiating OIH from symptoms of opioid tolerance or withdrawal.

AutoGenomics has received approval for the AvertD™ test, a prescription-only genetic risk assessment test for assessing whether certain individuals may have an increased likelihood of developing opioid use disorder (OUD). This is the first test approved for this use. The test is intended for use before first exposure to oral opioid pain medications in patients being considered for a 4- to 30-day prescription for the treatment of acute pain. It is administered by a trained HCP by collecting a DNA sample through swabbing a consenting adult patient’s cheek. The test should only be used in adults who have not previously used oral opioid analgesics. Certain genetic variants evaluated by the test may be associated with an increased risk for OUD. However, test results should only be utilized as a component of the risk assessment for OUD and should not be used solely for deciding whether to initiate opioid therapy. Additional details, including post-marketing requirements and a prior advisory committee meeting, are available from the FDA.

INFLUENZA UPDATES

The CDC is reporting influenza-like illness (ILI) for the week ending January 20, 2024 (week 3). Seasonal influenza activity is elevated in most parts of the U.S.; however, several key influenza indicators decreased or remained stable for the third week in a row (e.g., hospitalizations, HCP visits for respiratory illness). The most frequently reported influenza viruses this week were A(H1N1). The FDA is reporting available product from all manufacturers of antiviral influenza medications.

COVID-19: NOTABLE DEVELOPMENTS

A CDC analysis reported in an MMWR found no association between use of oral antiviral treatments for SARS-CoV-2 and COVID rebound. Symptoms observed with rebound were mild and no hospitalizations or deaths occurred. Based on these findings, data suggest that per NIH COVID treatment guidelines, the potential for viral rebound should not impede HCPs from prescribing antiviral therapies as indicated, since early use prevents hospitalizations and deaths in mild-to-moderate COVID patients who are at risk for severe disease. A separate MMWR report further detailed that SARS-CoV-2 RNA rebound can occur with or without nirmatrelvir/ritonavir (Paxlovid™) treatment.

As of January 20, 2024, data from the CDC demonstrate that the JN.1 (Omicron) variant is responsible for an estimated 85.7% of COVID cases in the U.S. Data published from the CDC in an MMWR reveal that persons ≥ 65 years of age or on dialysis who received a bivalent mRNA COVID vaccine were about 50% less likely to experience a COVID-related thromboembolic event compared to those who only received an original monovalent vaccine.

FDA SPOTLIGHT

The FDA has published its annual report on new drug approvals, highlighting 55 novel drug approvals in 2023. More than half of these approvals received Orphan Drug designation based on their targeting of rare diseases affecting      < 200,000 people in the U.S. Novel rare disease therapies approved in 2023 include omaveloxolone (Skyclarys®), the first treatment for Friedreich’s ataxia (an inherited, degenerative disease), trofinetide (Daybue™), the first treatment for patients aged 2 years with Rett syndrome (a genetic neurological disorder), and pozelimab-bbfg (Veopoz™), the first drug to treat CHAPLE disease (immune system disease). Drug approvals in 2023 also include therapies for rare cancers/tumors, including therapies for Mantle cell lymphoma, nasopharyngeal carcinoma, large B-cell lymphoma, and desmoid tumors. Of the 55 novel drugs approved, 36% were first-in-class agents with a unique mechanism of action. There were also several notable approvals, including nirsevimab-alip (Beyfortus™), approved for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season and certain high-risk children up to 24 months of age through their second RSV season. The report also captures other 2023 approvals, including new indications of existing drugs, as well as expanded populations and new formulations, new dosage forms, biosimilars, and over-the-counter (OTC) actions.

The agency has issued a Drug Safety Communication revising the prescribing information for the osteoporosis medication denosumab (Prolia®) to include a Boxed Warning on the risk of severe hypocalcemia in patients with advanced chronic kidney disease (CKD), including those on dialysis. The risk seems to be greater in patients with CKD who also have mineral and bone disorder (CKD-MBD). Patients with severe hypocalcemia may be asymptomatic or exhibit confusion, seizures, heart arrhythmias, syncope, facial twitches, muscle spasms, as well as weakness, tingling, or numbness. Patients taking denosumab who have advanced CKD and severe hypocalcemia can experience serious harms, including hospitalization and death.

The FDA has announced it is creating a new advisory committee for evaluating potential therapies for genetic metabolic diseases: Genetic Metabolic Diseases Advisory Committee. Although most of these diseases are rare, these conditions have significant morbidity and can result in increased mortality. The committee will provide independent advice and recommendations on products used for the diagnosis, prevention, or treatment of genetic metabolic diseases. Nine voting members who are experts in metabolic genetics, inborn errors of metabolism, small population study design, translational science, pediatrics, epidemiology or statistics, as well as related specialties will be invited to serve.

WEIGHT MANAGEMENT CORNER

The FDA is evaluating three potential safety signals (alopecia, aspiration, suicidal ideation) with glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) based on the FDA’s Adverse Event Reporting System (FAERS) from July to September 2023. The agency has also issued a Drug Safety Communication providing an update on its ongoing evaluation of reports of suicidal thoughts and actions in patients taking GLP-1 RAs. After preliminary review of data from FAERS and clinical trials, evidence has not shown an association between GLP-1 RAs and suicidal thoughts/actions. However, the FDA will perform additional evaluations including a meta-analysis and post-marketing data analysis from the Sentinel System. Patients are instructed not to stop taking GLP-1 RAs without consulting with their HCP. HCPs should monitor patients for new/worsening depression, suicidal thoughts, or unusual mood/behavior changes.

CLINICAL CORNER

The FDA has announced implementation of previously planned labeling updates for all (brand and generic) immediate-release (IR) and extended-release/long-acting (ER/LA) opioid analgesics. These required safety labeling updates were previously communicated in an April 2023 Drug Safety Communication and include the addition of language stating: (1) the risk of overdose increases as the dose increases for opioids; (2) IR opioids should not be used for an extended period of time unless a patient’s pain remains severe enough to necessitate their use and alternative treatments are not adequate; (3) a number of acute pain conditions treated in the outpatient setting do not need more than a few days of an opioid pain medicine; and (4) ER/LA opioids should be reserved for severe and persistent pain requiring an extended treatment duration with a daily opioid and for which alternative therapies are not adequate. Additional label updates include a new warning about opioid-induced hyperalgesia (OIH), in which opioid use leads to an increase in pain (hyperalgesia) or an increased sensitivity to pain (allodynia). Details were also added to aid in differentiating OIH from symptoms of opioid tolerance or withdrawal.

AutoGenomics has received approval for the AvertD™ test, a prescription-only genetic risk assessment test for assessing whether certain individuals may have an increased likelihood of developing opioid use disorder (OUD). This is the first test approved for this use. The test is intended for use before first exposure to oral opioid pain medications in patients being considered for a 4- to 30-day prescription for the treatment of acute pain. It is administered by a trained HCP by collecting a DNA sample through swabbing a consenting adult patient’s cheek. The test should only be used in adults who have not previously used oral opioid analgesics. Certain genetic variants evaluated by the test may be associated with an increased risk for OUD. However, test results should only be utilized as a component of the risk assessment for OUD and should not be used solely for deciding whether to initiate opioid therapy. Additional details, including post-marketing requirements and a prior advisory committee meeting, are available from the FDA.

INFLUENZA UPDATES

The CDC is reporting influenza-like illness (ILI) for the week ending January 20, 2024 (week 3). Seasonal influenza activity is elevated in most parts of the U.S.; however, several key influenza indicators decreased or remained stable for the third week in a row (e.g., hospitalizations, HCP visits for respiratory illness). The most frequently reported influenza viruses this week were A(H1N1). The FDA is reporting available product from all manufacturers of antiviral influenza medications.

COVID-19: NOTABLE DEVELOPMENTS

A CDC analysis reported in an MMWR found no association between use of oral antiviral treatments for SARS-CoV-2 and COVID rebound. Symptoms observed with rebound were mild and no hospitalizations or deaths occurred. Based on these findings, data suggest that per NIH COVID treatment guidelines, the potential for viral rebound should not impede HCPs from prescribing antiviral therapies as indicated, since early use prevents hospitalizations and deaths in mild-to-moderate COVID patients who are at risk for severe disease. A separate MMWR report further detailed that SARS-CoV-2 RNA rebound can occur with or without nirmatrelvir/ritonavir (Paxlovid™) treatment.

As of January 20, 2024, data from the CDC demonstrate that the JN.1 (Omicron) variant is responsible for an estimated 85.7% of COVID cases in the U.S. Data published from the CDC in an MMWR reveal that persons ≥ 65 years of age or on dialysis who received a bivalent mRNA COVID vaccine were about 50% less likely to experience a COVID-related thromboembolic event compared to those who only received an original monovalent vaccine.

FDA SPOTLIGHT

The FDA has published its annual report on new drug approvals, highlighting 55 novel drug approvals in 2023. More than half of these approvals received Orphan Drug designation based on their targeting of rare diseases affecting      < 200,000 people in the U.S. Novel rare disease therapies approved in 2023 include omaveloxolone (Skyclarys®), the first treatment for Friedreich’s ataxia (an inherited, degenerative disease), trofinetide (Daybue™), the first treatment for patients aged 2 years with Rett syndrome (a genetic neurological disorder), and pozelimab-bbfg (Veopoz™), the first drug to treat CHAPLE disease (immune system disease). Drug approvals in 2023 also include therapies for rare cancers/tumors, including therapies for Mantle cell lymphoma, nasopharyngeal carcinoma, large B-cell lymphoma, and desmoid tumors. Of the 55 novel drugs approved, 36% were first-in-class agents with a unique mechanism of action. There were also several notable approvals, including nirsevimab-alip (Beyfortus™), approved for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season and certain high-risk children up to 24 months of age through their second RSV season. The report also captures other 2023 approvals, including new indications of existing drugs, as well as expanded populations and new formulations, new dosage forms, biosimilars, and over-the-counter (OTC) actions.

The agency has issued a Drug Safety Communication revising the prescribing information for the osteoporosis medication denosumab (Prolia®) to include a Boxed Warning on the risk of severe hypocalcemia in patients with advanced chronic kidney disease (CKD), including those on dialysis. The risk seems to be greater in patients with CKD who also have mineral and bone disorder (CKD-MBD). Patients with severe hypocalcemia may be asymptomatic or exhibit confusion, seizures, heart arrhythmias, syncope, facial twitches, muscle spasms, as well as weakness, tingling, or numbness. Patients taking denosumab who have advanced CKD and severe hypocalcemia can experience serious harms, including hospitalization and death.

The FDA has announced it is creating a new advisory committee for evaluating potential therapies for genetic metabolic diseases: Genetic Metabolic Diseases Advisory Committee. Although most of these diseases are rare, these conditions have significant morbidity and can result in increased mortality. The committee will provide independent advice and recommendations on products used for the diagnosis, prevention, or treatment of genetic metabolic diseases. Nine voting members who are experts in metabolic genetics, inborn errors of metabolism, small population study design, translational science, pediatrics, epidemiology or statistics, as well as related specialties will be invited to serve.

Drug information happenings & highlights

DRUG INFORMATION HIGHLIGHTS

  • Generic lisdexamfetamine dimesylate capsules are unavailable or in short supply from various manufacturers. This is primarily related to an active ingredient shortage. Takeda’s brand-name Vyvanse® capsules are available.
  • Due to increased demand, Eli Lilly’s tirzepatide (Mounjaro®) in the strength of 12.5 mg/0.5 mL is in limited supply through February 2024. Other strengths of the product are available.
  • Novo Nordisk has announced limited availability of the GLP-1 RA liraglutide (Victoza®) 6 mg/mL prefilled, single-patient-use pens through March 2024 due to shipping delays.
  • The FDA has previously reported a shortage of penicillin G benzathine (Bicillin® L-A) injection with estimated recovery in the second quarter of 2024. Given this shortage, temporary importation of benzathine benzylpenicillin (Extencilline®) injection has been approved with availability expected in the near term. The agency has posted instructions on how to prepare and administer Extencilline. Important differences between the two products are summarized in a healthcare provider letter. Benzathine benzylpenicillin is another name for penicillin G benzathine.
  • Insight voluntarily recalled one lot of the OTC product Americaine® 20% Benzocaine Topical Anesthetic Spray to the consumer level following detection of low levels of benzene (human carcinogen) in the propellant that sprays the product out of the can. Although serious adverse events related to this recall have not been reported, patients that have the recalled product should stop using the product immediately.
  • Azurity has voluntarily recalled one lot of dextroamphetamine sulfate tablets, USP (Zenzedi®) in the strength of 30 mg to the consumer level following a report of a bottle of Zenzedi 30 mg tablets containing carbinoxamine maleate tablets, an antihistamine.

DRUG INFORMATION HAPPENINGS

  • The American Diabetes Association (ADA) released their 2024 Standards of Care in Diabetes.
  • The Kidney Disease: Improving Global Outcomes (KDIGO) updated the clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (update to 2018 guidelines).
  • The American College of Cardiology (ACC)/American Heart Association (AHA) published a 2023 guideline update on the diagnosis and management of atrial fibrillation.
  • The Institute for Clinical and Economic Review (ICER) published a final evidence report evaluating the effectiveness and value of investigational sotatercept in patients with pulmonary arterial hypertension (PAH).
  • Eli Lilly has launched LillyDirect™, a website which aims to improve patient access to medications for diabetes, migraine, and obesity, including tirzepatide (Zepbound™). The site will offer educational information, access to independent HCPs (telehealth or in-person), and direct home delivery of select medications.
Glossary

CDC = Centers for Disease Control and Prevention

CHAPLE = CD55-deficient protein-losing enteropathy

DNA = deoxyribonucleic acid

HCP = health care professional

JAK = Janus kinase

MMWR = Morbidity and Mortality Weekly Report

mRNA = messenger ribonucleic acid

NIH = National Institutes of Health

REMS = Risk Evaluation and Mitigation Strategies

RNA = ribonucleic acid

RSV = respiratory syncytial virus

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2

USP = U.S. Pharmacopeia

Editorial team

EDITOR-IN-CHIEF: Maryam Tabatabai, PharmD

EXECUTIVE EDITOR: Anna Schreck Bird, PharmD

DEPUTY EDITORS: Erik Hamel, PharmD

Olivia Pane, PharmD, CDCES

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