FDA Approves Drug for Heart Disorder Caused by Transthyretin-Mediated Amyloidosis
FDA approved Attruby (acoramidis) to treat adults with cardiomyopathy (disorder that affects heart muscle) of wild-type or variant (hereditary) transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems.
ACTION: The U.S. Food and Drug Administration has approved Attruby (acoramidis) to treat adults with cardiomyopathy (disorder that affects heart muscle) of wild-type or variant (hereditary) transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems.
Attruby is taken orally, twice daily. Recommended dosing is available in the prescribing information.
DISEASE OR CONDITION: ATTR-CM is a rare and serious disease that affects the heart muscle. In patients with ATTR-CM, there is a build-up of protein deposits in the heart, causing the walls of the heart to become stiff, and making the left ventricle unable to properly relax and fill with blood (called cardiomyopathy). As the condition progresses, the heart can become unable to pump blood out adequately, causing heart failure.
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There are two types of ATTR-CM, hereditary ATTR-CM (hATTR-CM) and wild-type ATTR-CM (wATTR-CM). In hATTR-CM, which can run in families, there’s a variant in the transthyretin gene, which results in protein deposits in the heart. In wATTR-CM, there is no variant in the transthyretin gene.
While the true prevalence of ATTR-CM is unknown, increasing awareness and enhanced diagnostic tools have led to increasing estimates of the number of patients with ATTR-CM.
EFFECTIVENESS: The efficacy and safety of Attruby were evaluated in a multicenter, international, randomized, double-blind, placebo-controlled study in 611 adult patients with wild-type or hereditary (variant) ATTR-CM (NCT03860935).
The primary endpoint of the study included all-cause mortality and cumulative frequency of cardiovascular-related hospitalizations (CVH) over 30 months. At 30 months, more patients taking Attruby vs placebo were alive (81% vs 74%) and there were fewer CVH in those taking Attruby vs placebo (mean number of 0.3 vs 0.6 per year).
SAFETY INFORMATION: The most common adverse reactions were diarrhea and upper abdominal pain. Most of these gastrointestinal adverse reactions were categorized as mild and resolved without drug discontinuation.
DESIGNATIONS: Attruby received orphan drug designation for this indication.
Source: FDA Approves Drug for Heart Disorder Caused by Transthyretin-Mediated Amyloidosis. FDA. Published: November 25, 2024.
T-Wave Morphology Variation Improves Risk Stratification in Type 2 Long-QT Syndrome Beyond QTc Duration
This study demonstrates that the TMV index provides prognostic information beyond QTc duration in patients with LQT2. More negative TMV values were independently associated with an increased lifetime risk of cardiac events, whereas T-wave amplitude and the morphology combination score were not predictive of outcomes. TMV may enhance ECG-based risk stratification, particularly in patients with borderline or prolonged QTc intervals, pending validation in larger prospective multicenter studies.
KEY FINDINGS: This study demonstrates that quantitative assessment of T-wave morphology using the TMV index provides prognostic information beyond conventional QTc duration in patients with LQT2. More negative TMV values, reflecting greater T-wave morphological distortion and broader repolarization, were independently associated with a markedly higher lifetime risk of cardiac events after adjustment for established clinical and electrocardiographic risk markers. In contrast, traditional morphology metrics such as T-wave amplitude and the morphology combination score did not independently predict outcomes. These findings suggest that TMV may serve as a complementary ECG biomarker to improve risk stratification, particularly among patients with borderline or prolonged QTc intervals. Because this was a relatively small, exploratory cohort, larger prospective multicenter studies are required before routine clinical implementation.
BACKGROUND: Risk stratification in patients with genotype-confirmed type 2 long-QT syndrome (LQT2) remains challenging because corrected QT (QTc) duration alone does not fully capture arrhythmic risk. A substantial proportion of genetically affected individuals have borderline or normal QTc intervals despite remaining susceptible to cardiac events. This study evaluated whether a novel electrocardiographic marker, the T-wave morphology variation (TMV) index, could provide incremental prognostic information by quantifying T-wave morphology abnormalities relative to a large population-based reference.
DETAILS: This combined retrospective and prospective cohort study included 54 genotype-confirmed patients with LQT2 recruited from three tertiary cardiogenetic centers in Sweden. T-wave morphology was analyzed from resting 12-lead ECGs using a dynamic time-warping algorithm that generated the TMV index by comparing each patient's T wave with sex-, heart rate-, and lead-matched reference waveforms derived from 23,962 healthy participants in the UK Biobank. The primary outcome was the first lifetime cardiac event, defined as syncope or ventricular arrhythmia, while ventricular arrhythmia alone served as the secondary endpoint. Cox proportional hazards models evaluated the association between TMV and clinical outcomes after adjustment for QTc, sex, and the morphology combination score (MCS). Among the 54 patients, 32 experienced at least one cardiac event, including 28 with syncope and 11 with documented ventricular arrhythmia. A TMV threshold of <=-18.41 ms (25th percentile) identified patients at substantially higher risk of cardiac events. Low TMV was associated with a significantly increased risk of cardiac events in univariate analysis (HR, 3.505 [95% CI, 1.673-7.341]; P<0.001). The association remained significant after adjustment for QTc (HR, 2.92 [95% CI, 1.111-7.676]; P=0.03), QTc plus sex (HR, 3.375 [95% CI, 1.256-9.067]; P=0.016), and QTc, sex, plus MCS (HR, 4.061 [95% CI, 1.369-12.046]; P=0.012). Patients with TMV <=-18.41 ms experienced cardiac events more frequently than those with higher TMV (93% vs 43%), while ventricular arrhythmias occurred in 43% versus 10%, respectively. TMV also predicted ventricular arrhythmias in univariate analysis (HR, 4.978 [95% CI, 1.4-17.705]; P=0.013), although this association did not remain statistically significant after multivariable adjustment. Neither T-wave amplitude nor MCS independently predicted cardiac events in this cohort.
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Source: Gomez, N., Ramirez, J., Savelev, A. A., et al. Risk Stratification of Patients With Type 2 Long-QT Syndrome Through Analysis of T-Wave Morphology. Journal of the American Heart Association. 2026; 15(3). Published: June 23, 2026. DOI: 10.1161/JAHA.125.048388.
Ensitrelvir for Covid-19 Postexposure Prophylaxis in Household Contacts
Early initiation of a 5-day oral ensitrelvir regimen within 72 hours after symptom onset in an index patient significantly reduced the risk of developing Covid-19 among household contacts while maintaining a safety profile comparable to placebo. Clinical benefit was observed across major patient subgroups, including individuals at increased risk for severe disease, and treatment was associated with reduced household transmission. These findings support ensitrelvir as an effective postexposure prophylactic option for household contacts and suggest potential utility in other high-risk exposure settings where rapid outbreak control is needed.
KEY FINDINGS: Early initiation of a 5-day oral ensitrelvir regimen within 72 hours after symptom onset in an index patient significantly reduced the risk of developing Covid-19 among household contacts while maintaining a safety profile comparable to placebo. Clinical benefit was observed across major patient subgroups, including individuals at increased risk for severe disease, and treatment was associated with reduced household transmission. These findings support ensitrelvir as an effective postexposure prophylactic option for household contacts and suggest potential utility in other high-risk exposure settings where rapid outbreak control is needed.
BACKGROUND: Household transmission remains a major contributor to the spread of SARS-CoV-2, particularly among individuals at increased risk for severe Covid-19. Although vaccination and prior infection have reduced disease severity, waning immunity and emerging variants continue to sustain transmission. Previous trials evaluating oral antiviral agents for postexposure prophylaxis in household contacts have not demonstrated significant protection, highlighting the need for effective preventive therapies. This phase 3 trial evaluated whether oral ensitrelvir, a SARS-CoV-2 3C-like protease inhibitor, could prevent Covid-19 among household contacts exposed to an infected index patient.
DETAILS: This phase 3, double-blind, randomized, placebo-controlled trial was conducted between June 2023 and mid-September 2024 across the United States, Argentina, Japan, South Africa, and Vietnam. Eligible household contacts were 12 years of age or older, had a negative SARS-CoV-2 test at enrollment, and were randomized within 72 hours after symptom onset in the index patient. Participants received either ensitrelvir 375 mg on day 1 followed by 125 mg once daily on days 2-5 or matching placebo. The primary endpoint was laboratory-confirmed Covid-19 by day 10 in the modified intention-to-treat population, defined as RT-PCR positivity accompanied by at least one prespecified Covid-19 symptom lasting 48 hours or longer. Secondary endpoints included laboratory-confirmed SARS-CoV-2 infection regardless of symptoms, subgroup analyses, and safety outcomes. Overall, 2,387 household contacts were randomized, including 1,030 participants in the ensitrelvir group and 1,011 in the placebo group within the modified intention-to-treat population. The mean participant age was 42.4 years, 71.1% were enrolled within 48 hours after symptom onset in the index patient, and 37.0% had at least one risk factor for severe Covid-19. By day 10, laboratory-confirmed Covid-19 occurred in 2.9% of participants receiving ensitrelvir compared with 9.0% receiving placebo, corresponding to a risk ratio of 0.33 (95% CI, 0.22-0.49; P<0.001) and an approximate 67% relative risk reduction in the modified intention-to-treat population. In the intention-to-treat population, Covid-19 developed in 4.4% and 10.2% of participants, respectively (risk ratio, 0.43; 95% CI, 0.32-0.59; P<0.001). Laboratory-confirmed SARS-CoV-2 infection irrespective of symptoms was also lower with ensitrelvir (14.0% vs. 21.5%; risk ratio, 0.66; 95% CI, 0.55-0.79). Subgroup analyses demonstrated generally consistent efficacy across age groups and participants with risk factors for severe disease. Among participants with risk factors, Covid-19 developed in 2.4% of the ensitrelvir group compared with 9.9% of the placebo group. Ensitrelvir was also associated with a 34% relative reduction in household SARS-CoV-2 transmission. Adverse events occurred at similar frequencies in the ensitrelvir and placebo groups (15.1% vs. 15.5%), with serious adverse events reported in 0.2% of participants in each group. No Covid-19-related hospitalizations or deaths occurred. Transient reductions in high-density lipoprotein concentrations were observed with ensitrelvir but returned toward baseline by day 15 and were not associated with clinical events.
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Pharmacogenomic-Informed Antidepressant Prescribing in Australian Primary Care
In this pragmatic double-blind randomized controlled trial conducted in Australian primary care, pharmacogenomic-informed antidepressant prescribing did not improve depressive symptoms compared with prescribing guided by national therapeutic guidelines. Clinical outcomes, medication tolerability, adherence, and quality of life were similar between groups, while cost-effectiveness analyses did not support routine implementation of pharmacogenomic testing in this setting. These findings suggest that broad pharmacogenomic-guided antidepressant prescribing in general practice does not provide additional clinical benefit over guideline-based management, although targeted evaluation in carefully selected patient populations may warrant further investigation.
Summary
Findings from the PRESIDE Double-Blind Randomized Controlled Trial
[Posted 7/Jul/2026]
AUDIENCE: Family Medicine, Psychiatry
KEY FINDINGS: In this pragmatic double-blind randomized controlled trial conducted in Australian primary care, pharmacogenomic-informed antidepressant prescribing did not improve depressive symptoms compared with prescribing guided by national therapeutic guidelines. Clinical outcomes, medication tolerability, adherence, and quality of life were similar between groups, while cost-effectiveness analyses did not support routine implementation of pharmacogenomic testing in this setting. These findings suggest that broad pharmacogenomic-guided antidepressant prescribing in general practice does not provide additional clinical benefit over guideline-based management, although targeted evaluation in carefully selected patient populations may warrant further investigation.
BACKGROUND: Pharmacogenomic testing has been proposed as a strategy to individualize antidepressant selection by identifying CYP2D6 and CYP2C19 variants that influence drug metabolism. Although previous studies have suggested potential clinical benefits, evidence from pragmatic primary care settings remains limited. The Pharmacogenomic-Informed Antidepressant Prescribing for Moderate-to-Severe Depressive Symptoms in Australian General Practice (PRESIDE) trial evaluated whether pharmacogenomic-guided prescribing improves depression outcomes compared with guideline-based prescribing in routine general practice.
DETAILS: PRESIDE was a multicenter, double-blind, randomized controlled trial conducted in Australian general practice between May 26, 2021, and September 28, 2023. Of 5185 patients approached, 552 were randomized, and 550 participants (275 per group) were included in the intention-to-treat analysis. Participants with moderate-to-severe depressive symptoms were assigned in a 1:1 ratio to receive antidepressant prescribing recommendations based either on pharmacogenomic testing combined with Australian Therapeutic Guidelines or on Australian Therapeutic Guidelines alone. Pharmacogenomic reports incorporated CYP2D6 and CYP2C19 metabolizer phenotypes derived from saliva-based genotyping. The primary endpoint was change in Patient Health Questionnaire-9 (PHQ-9) score from baseline to 12 weeks after the prescribing report was received. Secondary outcomes included remission, treatment response, antidepressant-related adverse effects, medication adherence, prescribing congruence, quality of life, and cost-effectiveness. A total of 479 participants (87%) completed the primary 12-week outcome assessment. Depressive symptoms improved over time in both groups. At 12 weeks, the adjusted between-group difference in PHQ-9 change was 0.90 (95% CI, 0.06-1.75; standardized mean difference 0.23 [95% CI, 0.02-0.45]; p=0.036), indicating a small but greater improvement in depressive symptoms in the guideline-based control group. No significant between-group differences were observed at 4, 8, or 26 weeks. Remission at 12 weeks occurred in 11% of participants receiving pharmacogenomic-guided prescribing compared with 18% in the control group, corresponding to an adjusted difference of -7.22% (95% CI, -13.25 to -1.19) and an odds ratio of 0.530 (95% CI, 0.311-0.903; p=0.020). Treatment response rates did not differ significantly between groups (29% vs 32%; OR 0.874; 95% CI, 0.581-1.315; p=0.518). Approximately two-thirds of participants had an actionable CYP2D6 or CYP2C19 phenotype, yet subgroup analyses demonstrated no differential treatment benefit based on genotype. Antidepressant adherence, side-effect burden, health-related quality of life, and health-care utilization were comparable between groups. Economic analyses indicated that pharmacogenomic-guided prescribing was more costly and less effective than standard guideline-based care, although differences in costs and quality-adjusted life years were not statistically significant. No grade 2-5 adverse events occurred, and only one grade 1 adverse event related to an administrative reporting error was documented.
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Source: Saya, S., Chondros, P., Abela, A., et al. Pharmacogenomic-informed antidepressant prescribing for moderate-to-severe depressive symptoms in Australian general practice (PRESIDE): a double-blind, randomised controlled trial. The Lancet Primary Care. 2026; Published: June 25, 2026. DOI: 10.1016/j.lanprc.2026.100158
Efficacy and Safety of Bempedoic Acid in Patients Aged 75 Years and Above Stratified by Varying Statin Exposure
Bempedoic acid was well-tolerated with comparable efficacy and safety across all age categories, except for musculoskeletal disorders in patients receiving concomitant statins. The reduction in MACE-4 was not statistically different among younger and older individuals, supporting the goal of LDL-C lowering with bempedoic acid for cardiovascular prevention in older individuals aged 75 years and above.
Summary
Results From Phase 3 Studies of Bempedoic Acid
[Posted 29/Jun/2026]
AUDIENCE: Cardiology, Emergency Medicine, Internal Medicine
KEY FINDINGS: Bempedoic acid was well tolerated in patients aged >=75 years with efficacy and safety comparable with younger subgroups regardless of background statin usage. Bempedoic acid may be considered a viable strategy for managing hypercholesterolemia in adults, regardless of age.
BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of major vascular events across all age groups. Authors analyzed phase 3 studies of bempedoic acid to characterize the safety and efficacy in patients aged >=75 years with and without a concomitant statin.
DETAILS: Post hoc analysis of bempedoic acid in high-risk patients with cardiovascular disease by age from phase 3 placebo-controlled, randomized clinical trials: two 52-week primary hyperlipidemia studies with maximal background statin ("max-statins pool"), and 1 cardiovascular outcomes trial ("statin-intolerant pool). Efficacy (LDL-C, non–high-density lipoprotein cholesterol, total cholesterol, high-sensitivity C-reactive protein) and safety were evaluated. The max-statins pool included 3009 (2010 bempedoic acid, 999 placebo) patients. The statin-intolerant pool included 13 970 patients (6992 bempedoic acid, 6978 placebo). In total 7022 patients were aged 18 to <65 years; 7372 were aged 65 to <75 years; 2585 were aged >=75 years. Placebo-corrected mean percentage change in LDL-C at week 12 in the max-statin pool with bempedoic acid was -18.4% (95% CI, -21.3 to -15.6) for patients aged 18 to <65 years, -18.6% (95% CI, -21.2 to -16.1) for 65 to <75 years, and -18.3% (95% CI, -22.2 to -14.5) for >=75 years. In the statin-intolerant pool, LDL-C change was -21.9% (95% CI, -23.1 to -20.7) for patients aged 18 to <65 years, -22.9% (95% CI, -24.0 to -21.8) for 65 to <75 years, and -24.5% (95% CI, -26.2 to -22.7) for >=75 years. Frequency of adverse events compared with placebo was similar across the ages, but more frequent among patients >=75 years regardless of background statin. Cardiovascular event reduction was statistically comparable across all ages.
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Source:John Mancini, G. B., Lincoff, A. M., Goldberg, A. C., et al. Efficacy and Safety of Bempedoic Acid in Patients Aged >=75 Years Stratified by Varying Statin Exposure: Results From Phase 3 Studies of Bempedoic Acid. Journal of the American Heart Association. Published: June 23, 2026. DOI: 10.1161/JAHA.125.04789
FDA Approves First Single-Dose Generic Treatment for Influenza
FDA approved the first generic single-dose baloxavir marboxil tablet for influenza in patients aged 5 years and above, ahead of the 20262027 flu season. Approved for both acute uncomplicated influenza treatment (within 48 hours of symptom onset) and post-exposure prophylaxis, this milestone may improve access, affordability, and ease of antiviral use in clinical practice.
KEY FINDINGS:
- FDA approved the first generic form of baloxavir marboxil tablets.
- Approved for patients aged 5 years and older.
- Indications include acute uncomplicated influenza treatment and post-exposure prophylaxis.
- Treatment eligibility requires symptom duration of no more than 48 hours.
- Contraindicated in patients with hypersensitivity to baloxavir marboxil or formulation ingredients.
- Common adverse effects: diarrhea, bronchitis, nausea, sinusitis, and headache.
- In the U.S., nine out of 10 prescriptions filled are for generic drugs.
- Approval granted to Norwich Pharmaceuticals, Inc.
BACKGROUND: The U.S. Food and Drug Administration (FDA) announced approval of the first generic version of baloxavir marboxil tablets, previously marketed as Xofluza. This approval introduces the first single-dose generic option for both treatment and post-exposure prophylaxis of influenza. The approval was issued ahead of the 2026–2027 influenza season with the objective of expanding access to generic medications and supporting public health preparedness.
DETAILS: Generic baloxavir marboxil tablets are approved for use in patients aged 5 years and older. Indications include treatment of acute uncomplicated influenza in individuals who have experienced symptoms for no more than 48 hours and who are either otherwise healthy or at elevated risk for influenza-related complications. The medication is also approved for post-exposure prophylaxis following contact with an infected individual.
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The drug is contraindicated in patients with known hypersensitivity to baloxavir marboxil or any formulation components. Safety considerations include warnings regarding increased incidence of treatment-emergent resistance in patients younger than 5 years of age.
Common adverse effects reported include diarrhea, bronchitis, nausea, sinusitis, and headache.
FDA approval of generic baloxavir marboxil provides an additional therapeutic option for influenza management through a single-dose regimen. Increased availability of generic alternatives may support broader patient access and affordability while maintaining treatment availability before the upcoming flu season.
Copyright © Skyscape Editorial Team. All rights reserved.
Source: News Release: FDA Approves First Single-Dose Generic Treatment for Influenza.. FDA. Published: June 17, 2026.
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