CARDIOVASCULAR DISEASE
New therapy may decrease risk factor
Lipoprotein(a), a presumed risk factor for atherosclerotic cardiovascular disease, was significantly reduced in patients taking olpasiran therapy in a study published in the New England Journal of Medicine.
The authors conducted a randomized, double-blind, placebo-controlled, dose-finding trial including patients with established atherosclerotic cardiovascular disease and lipoprotein(a) concentration of more than 150 nmol/L. The patients were randomly assigned to receive subcutaneous administrations of one of four doses of olpasiran (10 mg every 12 weeks, 75 mg every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or a matching placebo. The primary endpoint was the percent change in lipoprotein(a) concentration from baseline to week 36.
Lipoprotein(a) concentration increased by a mean of 3.6% in the placebo group. However, in those with the olpasiran therapy, lipoprotein(a) concentration was substantially reduced resulting in placebo-adjusted mean percent changes of -70.5% with the 10-mg dose, -97.4% with the 75-mg dose, -101.1% with the 225-mg dose administered every 12 weeks, and -100.5% with the 225-mg dose administered every 24 weeks.
The most common adverse events reported with the use of olpasiran were injection site reactions, primarily pain.
The authors say that larger and longer studies are warranted to determine the effect of olpasiran on cardiovascular disease.
Reference: O'Donoghue ML, Rosenson RS, Gencer B, et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N Engl J Med. 2022;387(20):1855-1864. doi:10.1056/nejmoa2211023.
MPOX
Single-dose vaccine offers some protection
A single dose of JYNNEOS, a vaccine indicated for the prevention of mpox disease in adults 18 years of age and older determined to be at high risk for mpox infection, may provide some protection to at-risk individuals, according to a paper published in JAMA Network.
The paper's authors analyzed the vaccination status of 5,402 individuals with mpox between July 31 and September 3, 2022.1 Too few at-risk individuals reportedly did not complete a series (two doses) of the vaccine to assess the full effects.
About 85% of cases of mpox infection occurred among unvaccinated individuals-only 1.4% received at least one dose of JYNNEOS at least 14 days before illness. About 5% of cases occurred in those who had received at least one dose 13 days or fewer before the illness. A further 8% of cases occurred in those with unknown vaccination status.
The CDC expects peak immunity to occur 14 days after the second dose of JYNNEOS; however, its duration is currently unknown.2
It is recommended that two doses of JYNNEOS be administered via subcutaneous injection 4 weeks apart; however, the second dose may be given up to 35 days after the first dose. Clinicians are advised against giving a second dose before the minimum 28-day period. In some circumstances, a second dose may be given after 24 days. There is no maximum interval, and the second dose can be given as soon as possible without needing to restart or add doses to the series.
References: 1. Kuehn BM. Single Monkeypox vaccine dose provides some protection. JAMA. 2022;328(18):1801. doi:10.1001/jama.2022.18452.
2. Centers for Disease Control and Prevention. JYNNEOS vaccine. 2022. http://www.cdc.gov/poxvirus/monkeypox/interim-considerations/jynneos-vaccine.htm. Accessed November 10, 2022.
FOOD ALLERGIES
Survey details EAI access gaps
Expanding epinephrine autoinjector (EAI) use and access among adults with a food allergy (FA) should be a priority for the healthcare team, argue the authors of a paper published in Annals of Allergy, Asthma & Immunology.
They gave an online, IRB-exempt survey developed by a multidisciplinary team of patient advocacy groups, physicians, caregivers, and survey methodologists to a nationally representative group of adults with FA.
About 1,000 adults completed the survey, in which 61% self-identified as White; 16% as Black; 15% as Hispanic; and 7% as Asian, Native American, or other. Over half (52%) reported having been prescribed an EAI.
The top reasons for access gaps were a lack of indication from a physician that the patient needed the device and that the patient did not believe they needed one.
EAI prescription was highest among those with private health insurance (59% through an employer, 68% self-purchased) and lowest among those on Medicare (48%) and Medicaid (51%). About 33% said they had an unexpired EAI, and 25% always had access to EAIs. About 36% said they believed EAIs could cause life-threatening adverse reactions.
The average out-of-pocket cost for an EAI was $476.
Reference: Yost J, Brown E, Winders T, et al. Epinephrine autoinjector utilization and access in a nationally representative food-allergic adult sample. Ann Allergy Asthma Immunol. 2022;129(5). doi:10.1016/j.anai.2022.08.527.
MYELOMA
New treatment gains accelerated approval
Teclistamab-cqyv (TECVAYLI) was granted accelerated approval by the FDA. The treatment is indicated for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This is reportedly the first bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager for the disease.
Accelerated approval was based on the results of MajesTEC-1, a single-arm, multicohort, open-label, multicenter study.
The population studied included 110 patients with at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Patients also had not received prior BCMA-targeted therapy to be included.
The main efficacy outcome, the overall response rate as determined by an independent review committee assessment using International Myeloma Working Group 2016 criteria, was 61.8%.
The median follow-up time was 7.4 months. At 6 months, the duration was estimated to be about 90.6%; at 9 months, 66.5%.
Prescribing information for teclistamab-cqyv includes a boxed warning for potentially lethal cytokine release syndrome; neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome; and serious and life-threatening reactions.
The most common adverse reactions reported with teclistamab-cqyv were pyrexia, cytokine release syndrome, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. Grade 3 to 4 lab abnormalities included decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.
References: Center for Drug Evaluation and Research. FDA approves teclistamab-cqyv for relapsed or refractory multiple myel. U.S. Food and Drug Administration. 2022. http://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tecli. Accessed November 15, 2022.
HEPATIC CANCER
New treatment approved
Tremelimumab (Imjudo), in combination with durvalumab (Imfinzi), has been approved by the FDA for the treatment of adult patients with unresectable hepatocellular carcinoma (HCC).
The treatment is a novel dose and schedule consisting of a single dose of the anti-CTLA-4 antibody tremelimumab 300 mg added to anti-PD-L1 antibody durvalumab 1,500 mg followed by durvalumab every 4 weeks. The infusion regimen is called Single Tremelimumab Regular Interval Durvalumab (STRIDE).
Approval was based on the results of the HIMALAYA, a global, open-label, Phase III trial. Most of the 1,171 patients included in the trial had unresectable advanced HCC and no previous systemic treatment and were not eligible for locoregional therapy. They were randomly assigned to one of three arms: tremelimumab 300 mg as a one-time single I.V. infusion plus durvalumab 1,500 mg I.V. on the same day, followed by durvalumab 1,500 mg I.V. every 4 weeks; durvalumab 1,500 mg I.V. every 4 weeks; or sorafenib 400 mg orally twice daily until disease progression or unacceptable toxicity. The study's primary objective was the overall survival of those on STRIDE versus sorafenib. The secondary objective was noninferiority.
In total, 393 patients were assigned to STRIDE, 389 to durvalumab, and 389 to sorafenib. The median overall survival was: STRIDE, 16.43 months; durvalumab, 14.16 months; and sorafenib, 13.77 months. Overall survival at 36 months was 30.7%, 24.7%, and 20.2%, respectively. The overall survival for STRIDE versus sorafenib was 0.78. Durvalumab monotherapy was noninferior to sorafenib. Median progression-free survival was not significantly different among the three groups.
Adverse events were reported in 50.5% of those on STRIDE, 37.1% on durvalumab, and 52.4% on sorafenib.
References: Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer. News Release. AstraZeneca. October 24, 2022. https://bit.ly/3Fbwx1w. Accessed November 15, 2022.
Abou-Alfa GK, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab and durvalumab as first-line therapy in patients with unresectable hepatocellular carcinoma: HIMALAYA. J Clin Oncol. 2022;40(suppl 4):379. doi:10.1200/JCO.2022.40.4_suppl.379.\