HIV

New drug for experienced patients

The FDA has approved lenacapavir (Sunlenca, Gilead) for the treatment of HIV-1 infection in heavily treatment-experienced (HTE) adults with multidrug resistant (MDR) HIV-1 infection failing their current antiretroviral (ARV) regimen due to resistance, intolerance, or safety considerations.¹

Lenacapavir is a long-acting, potent inhibitor of the HIV capsid protein with in vitro activity against viral strains resistant to other ARV therapies.²

The approval was based on the results of a Phase 2/3 CAPELLA trial that evaluated lenacapavir in combination with an optimized background regimen in people with MDR HIV-1 who are HTE.^2,3 Participants as a whole had taken a median of nine ARV medications before the trial. The trial included 36 patients randomly assigned to receive lenacapavir or placebo 2:1 for 14 days, in addition to their failing regimen (functional monotherapy).

Eighty-three percent of patients who were randomly allocated to receive lenacapavir in addition to an optimized background regimen achieved an undetectable viral load at week 52.¹ They also achieved a mean increase in CD4 count of 82 cells per mcL.

Lenacapavir is contraindicated for concomitant administration with strong CYP3A inducers.¹ The most common adverse reactions reported with the use of lenacapavir are injection site reactions and nausea.¹

References: 1. Sunlenca^(R) (lenacapavir) receives FDA approval as a first-in-class, twice-yearly treatment option for people living with multi-drug resistant HIV. 2022. http://www.gilead.com/news-and-press/press-room/press-releases/2022/12/sunlenca-. Accessed January 9, 2023.

2. The National Institutes of Health. Lenacapavir. 2022. https://clinicalinfo.hiv.gov/en/drugs/lenacapavir/health-professional. Accessed January 9, 2023.

3. Study to evaluate the safety and efficacy of Lenacapavir (GS-6207) in combination with an optimized background regimen (OBR) in heavily treatment experienced participants living with HIV-1 infection with multidrug resistance - study results. 2022. ClinicaTrials.gov. https://clinicaltrials.gov/ct2/show/results/NCT04150068. Accessed January 9, 2023.

VACCINES

Malaria vaccine shows promise

A three-dose regimen of Plasmodium falciparum sporozoite (PfSPZ) vaccine demonstrated safety and vaccine efficacy (VE) against malaria infection in malaria-experienced adults, according to a paper published in Science Translational Medicine.¹

PfSPZ is a metabolically active, nonreplicating whole parasite vaccine. In a clinical trial, it demonstrated safety and VE against endemic P. falciparum for 6 months in Malian adults receiving a five-dose regimen.

The vaccine was tested in an open-label dose escalation trial with 32 participants, followed by a double-blind, randomized, placebo-controlled trial with 80 participants in 2017 randomized to receive three doses of 2.7 x 10⁶ PfSPZ (N = 39) or normal saline (N = 41) just before malaria season.

Artesunate monotherapy was administered before the first and last vaccinations to clear parasitemia. Thick blood smear microscopy was performed on samples collected during the illness and every 4 weeks for 72 weeks after the last vaccination, including two 6-month malaria transmission seasons.

Safety outcomes were assessed in 80 participants who received at least one dose and VE for 79 participants who received three vaccinations.

The only symptom that differed between groups was myalgia. The VE risk ratio was 38% at 6 months, and 15% at 8 months. The VE hazard ratio was 48% and 46% at 6 and 18 months. Antibodies to P. falciparum circumsporozoite protein and PfSPZ were higher in protected versus unprotected recipients 2 weeks after the last dose.

Reference: 1. Sirima SB, Ouedraogo A, Tiono AB, et al. A randomized controlled trial showing safety and efficacy of a whole sporozoite vaccine against endemic malaria. Sci Transl Med. 2022;14(674). doi:10.1126/scitranslmed.abj3776.

ANTIBIOTIC RESISTANCE

Hotspots for resistance in Western Pacific and South-East Asia

Wastewater and wastewater treatment plants of the WHO Western Pacific region (WPR) and the WHO South-East Asia region (SEAR), including in China and India, are potential hotspots for developing antibiotic resistance, according to a paper published in The Lancet.¹

Researchers conducted a systematic review of empirical studies that measured antibiotic concentrations in aquatic environments between 2006 and 2019 and a probabilistic environmental hazard assessments approach. The researchers also included measured environmental concentrations and predicted no-effect concentrations (PNECs). Lastly, they determined the relative contributions of potential sources of antibiotic contamination in waterways, such as hospitals, municipals, livestock, and pharmaceutical manufacturing for each antibiotic.

In all, 218 and 22 relevant studies were included from the WPR and SEAR, respectively. These studies included 168 and 15 from China and India, respectively.

Ninety-two antibiotics in the WPR and 45 in the SEAR were detected in various aquatic compartments. The highest antibiotic concentrations most likely to exceed PNECs were observed in wastewater and influents and effluents of wastewater treatment plants. The greatest risk for developing resistance existed in tap or drinking water of the WPR and China for ciprofloxacin.

Reference: 1. Hanna N, Tamhankar AJ, Stalsby Lundborg C. Antibiotic concentrations and antibiotic resistance in aquatic environments of the who western pacific and south-East Asia Regions: a systematic review and probabilistic environmental hazard assessment. Lancet Planet Health. 2023;7(1). doi:10.1016/s2542-5196(22)00254-6.

PRECISION MEDICINE

Leukemia pharmacotyping, may serve as blueprint

Pharmacotyping, defining a patient's drug sensitivity phenotype, led to alternative therapeutic strategies for children with acute lymphoblastic leukemia (ALL) and may serve as a blueprint for precision medicine.¹

The authors of the paper published in Nature Medicine analyzed samples from 805 children with newly diagnosed ALL who were participating in three consecutive clinical trials. The authors determined the ex vivo sensitivity of primary leukemia cells to 18 therapeutic agents across 23 molecular subtypes defined by leukemia genomics.

The authors found a wide variability in drug response and that some ALL subtypes exhibited the greatest sensitivity to L-asparaginase and glucocorticoids. Leukemia's sensitivity to these two agents was highly associated with minimal residual disease (MRD), although with distinct patterns and only in B cell ALL. Furthermore, six patient clusters based on ALL pharmacotypes were associated with event-free survival, even after adjusting for MRD.

Reference: 1. Lee SH, Yang W, Gocho Y, et al. Pharmacotypes across the genomic landscape of pediatric acute lymphoblastic leukemia and impact on treatment response. Nat Med. 2023;29(1):170-179. doi:10.1038/s41591-022-02112-7.

COVID-19 VACCINATION

MIS-C not associated with serious adverse reactions from mRNA vaccines

Multisystem inflammatory syndrome in children (MIS-C) was not associated with an increased risk of serious adverse reactions following COVID-19 vaccination.¹

The results, published in JAMA Network Open, suggest that the safety profile of vaccines (namely BNT162b2) appears to be similar to that of the general population.

The authors of the paper performed a multicenter cross-sectional study involving 185 participants who had a prior diagnosis of MIS-C and were eligible for any COVID-19 vaccination. They were surveyed between December 13, 2021, and February 18, 2022, regarding COVID-19 vaccination status and adverse reactions.

About 50% (185) received at least 1 vaccine dose; 136 vaccinated patients (73.5%) were male, and the median age was 12.2 years. Almost all (98.9%) received the BNT162b2 mRNA vaccine.

Nine months was the median time from MIS-C diagnosis to the first vaccination. Minor adverse reactions were observed in 90 patients (48.6%) and were most often arm soreness and/or fatigue. These reactions were treated with medication, most commonly acetaminophen or ibuprofen. Four patients sought medical evaluation but did not require testing or hospitalization. None of the patients exhibited serious adverse events, including myocarditis or recurrence of MIS-C.

Reference: 1. Elias MD, Truong DT, Oster ME, et al. Examination of adverse reactions after COVID-19 vaccination among patients with a history of multisystem inflammatory syndrome in children. JAMA Netw Open. 2023;6(1). doi:10.1001/jamanetworkopen.2022.48987.

MULTIPLE SCLEROSIS

New drug reduces relapse and brain lesions

The FDA has approved ublituximab-xiiy (Briumvi, TG Therapeutics) for the treatment of relapsing forms of multiple sclerosis (MS) in adults, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

Ublituximab-xiiy is a CD20-directed cytolytic antibody that enhances antibody-dependent cellular cytolysis and produces B-cell depletion.^1,2

In clinical trials, ublituximab-xiiy was shown to lower annualized relapse rates and resulted in fewer brain lesions on MRI than teriflunomide over 96 weeks. However, it did not result in a significantly lower risk of worsening disability.

Before the first dose is administered, patients must be screened for hepatitis B virus infection and current levels of quantitative serum immunoglobulin. Ublituximab-xiiy is contraindicated in those with an active hepatitis B virus infection and a history of life-threatening infusion reactions to the drug.

The most common adverse reactions reported when using ublituximab-xiiy include infusion reactions and upper respiratory tract infections.

References: 1. National Multiple Sclerosis Society. FDA approves Briumvi(TM) (ublituximab-xiiy) for relapsing MS. 2022. http://www.nationalmssociety.org/About-the-Society/News/FDA-Approves-Briumvi%e2%. Accessed January 10, 2023.

2. Steinman L, Fox E, Hartung H-P, et al. Ublituximab versus teriflunomide in relapsing multiple sclerosis. N Engl J Med. 2022;387(8):704-714. doi:10.1056/nejmoa2201904.