Clinical News: May 2024

May 30, 2024

Your monthly source for drug information highlights

Clinical News

Your monthly source for drug information highlights

Hot topic

FDA ALERT ON PREGNANCY RISKS WITH OFF-LABEL THIOPURINE USE

The U.S. Food and Drug Administration (FDA) has reported rare cases of intrahepatic cholestasis of pregnancy (ICP) associated with the use of thiopurines. This class of immunosuppressant medications includes azathioprine, 6-mercaptopurine, and 6-thioguanine. Although these agents are not FDA-approved for inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis) or systemic lupus erythematosus (SLE), practice guidelines from the American Gastroenterological Association (AGA) and the American College of Rheumatology (ACR) include azathioprine and 6-mercaptopurine as potential treatment options that could be continued during pregnancy for appropriate patients. Product labeling for these agents includes the risk of embryofetal toxicity when used during pregnancy and the risk of hepatotoxicity; however, the FDA is requiring label updates for these medications to include additional warnings on the risk of ICP associated with thiopurines during pregnancy. Labeling will be updated to include that post-marketing cases of ICP have occurred in individuals treated with thiopurines during pregnancy, and use of these medications should be discontinued in pregnant persons who develop ICP. The FDA does note that symptoms of ICP, as well as elevated bile acid levels, showed improvement following discontinuation of azathioprine in this setting.

More trending topics

BEHAVIORAL HEALTH CORNER

The Psychopharmacologic Drugs Advisory Committee will convene on June 4, 2024 to discuss an NDA for midomafetamine (MDMA) capsules from Lykos Therapeutics. The psychedelic MDMA is being evaluated for the treatment of post-traumatic stress disorder (PTSD). The overall benefits versus risks of the therapy will be discussed as well as the public health impact. Background documents will be available no later than two business days prior to the meeting on the FDA web page.

Shortages of stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) continue to be reported. Availability of generic methylphenidate HCl extended-release (ER) tablets is variable depending on the manufacturer. Shortages of the generic version of Vyvanse, lisdexamfetamine dimesylate capsules and chewable tablets persist. Generic amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate immediate release (IR) tablet shortages also continue from select manufacturers.

The FDA has cleared MamaLift Plus for use. MamaLift Plus is an 8-week, prescription‐only digital therapeutic to provide neurobehavioral interventions to patients ≥ 22 years old with mild to moderate postpartum depression (PPD), as an adjunct to clinician‐managed outpatient care. MamaLift Plus delivers digital Cognitive Behavioral Therapy, Behavioral Activation Therapy, Interpersonal Therapy, and Dialectical Behavior Therapy for PPD by addressing maladaptive behaviors, routines, and dysfunctional thoughts. Curio Digital Therapeutics’ MamaLift Plus is used on a mobile device (e.g., smartphone, tablet) and will be available this summer for download from the App Store® and Google Play.

WEIGHT MANAGEMENT CORNER

Results from the STEP-HFpEF DM (Semaglutide Treatment Effect in People with Obesity and Heart Failure with Preserved Ejection Fraction and Diabetes Mellitus) trial have been published in The New England Journal of Medicine. In the study, patients (n=616) with heart failure with preserved ejection fraction, a body-mass index of ≥ 30 kg/m2, and type 2 diabetes were randomized to receive once-weekly SC semaglutide (2.4 mg) or placebo for 52 weeks. The primary endpoints evaluated the change from baseline in a cardiomyopathy questionnaire assessing symptoms/physical limitations, and the change from baseline in body weight. For both coprimary endpoints, a statistically significant improvement was found with semaglutide compared to placebo (p<0.001 for both). The average change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (range, 0 to 100 with higher scores demonstrating fewer symptoms and physical limitations) was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4). The average percentage change in body weight was -9.8% with semaglutide compared with -3.4% with placebo (estimated difference, −6.4%; 95% CI, −7.6 to −5.2). Serious adverse events were also less common in semaglutide-treated patients than placebo patients (17.7% versus 28.8%, respectively). Authors concluded that semaglutide, titrated to 2.4 mg given SC weekly, resulted in greater reductions in heart failure-related symptoms and physical limitations as well as more weight loss compared to placebo after one year.

The FDA is currently reporting shortages of GLP-1 agonists that are indicated for select patients as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management. This includes Novo Nordisk’s semaglutide (Wegovy) which has limited availability in the strengths of 0.25 mg/0.5 mL, 0.5 mg/0.5 mL, and 1 mg/0.5 mL due to increased demand. The 1.7 mg/0.75 mL and 2.4 mg/0.75 mL injections of Wegovy remain available. Novo Nordisk’s liraglutide (Saxenda) also has limited availability as well as the liraglutide (Victoza) formulation indicated for select patients with type 2 diabetes. Eli Lilly’s tirzepatide (Zepbound) also has limited availability in most strengths as does the tirzepatide (Mounjaro) formulation indicated as an adjunct to diet and exercise in adults with type 2 diabetes.

BIOSIMILAR CORNER

The FDA has published an FDA Voices titled, “A Milestone in Facilitating the Development of Safe and Effective Biosimilars” which highlights the approval of the 50th biosimilar. At the time of the agency’s report, biosimilars have been approved by the FDA for 15 different reference products and are indicated to treat a variety of illnesses ranging from rheumatoid arthritis and inflammatory bowel disease to certain cancers and osteoporosis. The FDA has also released a Summary of Accomplishments related to the Biosimilars Action Plan (BAP) and an update of the BAP, reinforcing the agency’s commitment to expansion of biosimilar product availability and usage. The four goals of the BAP include: (1) improvement in the efficiency of the development and approval process for biosimilars and interchangeable biologic products; (2) maximization of scientific as well as regulatory clarity for developers of biosimilar products; (3) development of effective communications to increase comprehension of these products; and (4) advancement of the adoption of biosimilars, identification of false/misleading claims about the products, and prevention of anti-competitive behaviors related to these products.

COVID-19 NOTABLE DEVELOPMENTS

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting previously planned for May 16, 2024 has been rescheduled to June 5, 2024. At the meeting, the Committee plans to make recommendations on the selection of strain(s) for the 2024–2025 Formula for COVID-19 vaccines, and the later date allows for additional time to compile surveillance data on recently circulating strains.

The CDC published an MMWR detailing the durability of the original monovalent mRNA vaccine effectiveness against COVID-19 Omicron-associated hospitalization in children and adolescents from 2021 to 2023. From December 2021 through October 2023, pediatric patients who received ≥ 2 doses of an original monovalent mRNA COVID-19 vaccine had 52% vaccine efficacy against COVID-19 hospitalization and 57% vaccine efficacy against COVID-19-related critical illness. This protection was observed when the last dose was given within 4 months before hospitalization; however, it decreased over time.

The CDC has published an MMWR as a follow-up to the February 28, 2024 ACIP recommendation that all persons aged ≥ 65 years receive one additional dose of any updated (2023–2024 Formula) COVID-19 vaccine. Options include the 2023–2024 Formula COVID-19 vaccines from Moderna, Novavax, or Pfizer-BioNTech. The additional dose in this patient population is recommended to increase immunity and lower the likelihood for severe COVID-19-associated illness. This follows the September 2023 ACIP recommendation for all persons at least six months old to receive an updated 2023–2024 Formula COVID-19 vaccine.

BEHAVIORAL HEALTH CORNER

The Psychopharmacologic Drugs Advisory Committee will convene on June 4, 2024 to discuss an NDA for midomafetamine (MDMA) capsules from Lykos Therapeutics. The psychedelic MDMA is being evaluated for the treatment of post-traumatic stress disorder (PTSD). The overall benefits versus risks of the therapy will be discussed as well as the public health impact. Background documents will be available no later than two business days prior to the meeting on the FDA web page.

Shortages of stimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) continue to be reported. Availability of generic methylphenidate HCl extended-release (ER) tablets is variable depending on the manufacturer. Shortages of the generic version of Vyvanse, lisdexamfetamine dimesylate capsules and chewable tablets persist. Generic amphetamine aspartate monohydrate, amphetamine sulfate, dextroamphetamine saccharate, and dextroamphetamine sulfate immediate release (IR) tablet shortages also continue from select manufacturers.

The FDA has cleared MamaLift Plus for use. MamaLift Plus is an 8-week, prescription‐only digital therapeutic to provide neurobehavioral interventions to patients ≥ 22 years old with mild to moderate postpartum depression (PPD), as an adjunct to clinician‐managed outpatient care. MamaLift Plus delivers digital Cognitive Behavioral Therapy, Behavioral Activation Therapy, Interpersonal Therapy, and Dialectical Behavior Therapy for PPD by addressing maladaptive behaviors, routines, and dysfunctional thoughts. Curio Digital Therapeutics’ MamaLift Plus is used on a mobile device (e.g., smartphone, tablet) and will be available this summer for download from the App Store® and Google Play.

WEIGHT MANAGEMENT CORNER

Results from the STEP-HFpEF DM (Semaglutide Treatment Effect in People with Obesity and Heart Failure with Preserved Ejection Fraction and Diabetes Mellitus) trial have been published in The New England Journal of Medicine. In the study, patients (n=616) with heart failure with preserved ejection fraction, a body-mass index of ≥ 30 kg/m2, and type 2 diabetes were randomized to receive once-weekly SC semaglutide (2.4 mg) or placebo for 52 weeks. The primary endpoints evaluated the change from baseline in a cardiomyopathy questionnaire assessing symptoms/physical limitations, and the change from baseline in body weight. For both coprimary endpoints, a statistically significant improvement was found with semaglutide compared to placebo (p<0.001 for both). The average change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (range, 0 to 100 with higher scores demonstrating fewer symptoms and physical limitations) was 13.7 points with semaglutide and 6.4 points with placebo (estimated difference, 7.3 points; 95% confidence interval [CI], 4.1 to 10.4). The average percentage change in body weight was -9.8% with semaglutide compared with -3.4% with placebo (estimated difference, −6.4%; 95% CI, −7.6 to −5.2). Serious adverse events were also less common in semaglutide-treated patients than placebo patients (17.7% versus 28.8%, respectively). Authors concluded that semaglutide, titrated to 2.4 mg given SC weekly, resulted in greater reductions in heart failure-related symptoms and physical limitations as well as more weight loss compared to placebo after one year.

The FDA is currently reporting shortages of GLP-1 agonists that are indicated for select patients as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management. This includes Novo Nordisk’s semaglutide (Wegovy) which has limited availability in the strengths of 0.25 mg/0.5 mL, 0.5 mg/0.5 mL, and 1 mg/0.5 mL due to increased demand. The 1.7 mg/0.75 mL and 2.4 mg/0.75 mL injections of Wegovy remain available. Novo Nordisk’s liraglutide (Saxenda) also has limited availability as well as the liraglutide (Victoza) formulation indicated for select patients with type 2 diabetes. Eli Lilly’s tirzepatide (Zepbound) also has limited availability in most strengths as does the tirzepatide (Mounjaro) formulation indicated as an adjunct to diet and exercise in adults with type 2 diabetes.

BIOSIMILAR CORNER

The FDA has published an FDA Voices titled, “A Milestone in Facilitating the Development of Safe and Effective Biosimilars” which highlights the approval of the 50th biosimilar. At the time of the agency’s report, biosimilars have been approved by the FDA for 15 different reference products and are indicated to treat a variety of illnesses ranging from rheumatoid arthritis and inflammatory bowel disease to certain cancers and osteoporosis. The FDA has also released a Summary of Accomplishments related to the Biosimilars Action Plan (BAP) and an update of the BAP, reinforcing the agency’s commitment to expansion of biosimilar product availability and usage. The four goals of the BAP include: (1) improvement in the efficiency of the development and approval process for biosimilars and interchangeable biologic products; (2) maximization of scientific as well as regulatory clarity for developers of biosimilar products; (3) development of effective communications to increase comprehension of these products; and (4) advancement of the adoption of biosimilars, identification of false/misleading claims about the products, and prevention of anti-competitive behaviors related to these products.

COVID-19 NOTABLE DEVELOPMENTS

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting previously planned for May 16, 2024 has been rescheduled to June 5, 2024. At the meeting, the Committee plans to make recommendations on the selection of strain(s) for the 2024–2025 Formula for COVID-19 vaccines, and the later date allows for additional time to compile surveillance data on recently circulating strains.

The CDC published an MMWR detailing the durability of the original monovalent mRNA vaccine effectiveness against COVID-19 Omicron-associated hospitalization in children and adolescents from 2021 to 2023. From December 2021 through October 2023, pediatric patients who received ≥ 2 doses of an original monovalent mRNA COVID-19 vaccine had 52% vaccine efficacy against COVID-19 hospitalization and 57% vaccine efficacy against COVID-19-related critical illness. This protection was observed when the last dose was given within 4 months before hospitalization; however, it decreased over time.

The CDC has published an MMWR as a follow-up to the February 28, 2024 ACIP recommendation that all persons aged ≥ 65 years receive one additional dose of any updated (2023–2024 Formula) COVID-19 vaccine. Options include the 2023–2024 Formula COVID-19 vaccines from Moderna, Novavax, or Pfizer-BioNTech. The additional dose in this patient population is recommended to increase immunity and lower the likelihood for severe COVID-19-associated illness. This follows the September 2023 ACIP recommendation for all persons at least six months old to receive an updated 2023–2024 Formula COVID-19 vaccine.

Drug information happenings & highlights

DRUG INFORMATION HIGHLIGHTS

  • Par has voluntarily recalled one lot of treprostinil injection 20 mg/20 mL to the consumer level due to potential silicone particulates in the product solution. Treprostinil is indicated for select patients with pulmonary arterial hypertension. The recalled product is distributed in 20 mL multidose vials as sterile solutions in water for injection.
  • Dr. Reddy’s has voluntarily recalled 6 lots of sapropterin dihydrochloride (Javygtor) powder for oral solution 100 mg to the consumer level due to powder discoloration in some packets resulting in decreased potency. The problem was identified during a stability test; customer complaints also had noted the issue. The drug is indicated to decrease blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia due to tetrahydrobiopterin-(BH4-) responsive phenylketonuria; it is indicated in conjunction with a Phe-restricted diet.
  • Teva will discontinue the manufacture of albuterol sulfate (ProAir Digihaler) 90 mcg metered powder inhalers; fluticasone propionate/salmeterol xinafoate (AirDuo Digihaler) 55 mcg/14 mcg, 113 mcg/14 mcg, and 232 mcg/14 mcg metered powder inhalers; and fluticasone propionate (ArmonAir Digihaler) 55 mcg, 113 mcg, and 232 mcg metered powder inhalers. Distribution of the Digihaler products in the U.S. will cease on June 1, 2024, and software/technical support for the Digihaler app and dashboard will also end on this date.
  • The FDA has granted clearance to Adherium’s Hailie® Smartinhaler® for use with AstraZeneca’s albuterol/budesonide (Airsupra) and budesonide/glycopyrrolate/formoterol fumarate (Breztri Aerosphere) inhalation devices. The Smartinhaler provides real-time data and insights on medication usage patterns and provides inhaler technique feedback. Airsupra is indicated for the as-needed treatment or prevention of bronchoconstriction and to reduce the risk of exacerbations in adults with asthma, and Breztri Aerosphere is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).
  • Amgen has announced that it will discontinue the manufacture of the Repatha Pushtronex® System for evolocumab on June 30, 2024; the SureClick Autoinjector for evolocumab will remain available. Amgen stated that this decision was made to maintain its high standards for the patient experience.
  • Pfizer has announced discontinuation of the brand-name antiarrhythmic Tikosyn (dofetilide) that is indicated for use in patients with atrial fibrillation/atrial flutter. Generic product remains available from multiple manufacturers.

DRUG INFORMATION HAPPENINGS

  • The Peripheral and Central Nervous System (CNS) Drugs Advisory Committee will convene on June 10, 2024 to discuss the BLA for Eli Lilly’s investigational IV donanemab. The monoclonal antibody is being reviewed for the treatment of early symptomatic Alzheimer’s disease.
  • The American College of Physicians (ACP) published guidelines on newer pharmacologic treatments in adults with type 2 diabetes mellitus. Agents addressed include SGLT2 inhibitors, GLP-1 receptor agonists, dual GLP-1/GIP agonists, DPP-4 inhibitors, and long-acting insulins.
  • The FDA has granted integrated continuous glucose monitoring (iCGM) designation to the Eversense® CGM system, indicating that the product can integrate with compatible medical devices (e.g., insulin pumps) as part of an automated insulin delivery system. The Eversense CGM is the first fully implantable device in the category and can be worn for up to six months.
  • GSK reported data from the long-term, phase 3, ZOSTER-049 follow-up trial of recombinant zoster vaccine (Shingrix). Vaccine efficacy was 79.7% in those ≥ 50 years old within year six to year 11 after vaccination and was 82% at year 11.
  • The U.S. Preventive Services Task Force (USPSTF) has issued final recommendations on screening for breast cancer which recommend biennial screening mammography for women between 40 and 74 years old (Grade B). Current evidence is inadequate to determine the benefits versus harms for screening mammography in women ≥ 75 years old (Grade I).

The content in this publication is not a substitute for professional medical advice. For questions regarding any medical condition or if you need medical advice, please contact your health care provider.

All brand names are property of their respective owners.

Glossary

ACIP = Advisory Committee on Immunization Practices

BLA = Biologics License Application

CDC = Centers for Disease Control and Prevention

COVID-19 = coronavirus 2019

DPP-4 = dipeptidyl peptidase-4

GIP = glucose-dependent insulinotropic polypeptide

GLP-1 = glucagon-like peptide-1

HCl = hydrochloride

IV = intravenous

MMWR = Morbidity and Mortality Weekly Report

mRNA = messenger ribonucleic acid

NDA = New Drug Application

SC = subcutaneous

SGLT2 = sodium-glucose cotransporter-2

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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