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.