COVID-19

WHO cannot recommend 2 drugs

The World Health Organization (WHO) says that current evidence is not enough to recommend the use of fluvoxamine, an antidepressant, or colchicine, a medication for gout, for the treatment of nonsevere COVID-19. No recommendation was made for either drug in patients with severe or critical illness, given limited or no data. The WHO goes so far as to suggest that "almost all well-informed patients would choose not to receive either [drug] for COVID-19."

Instead, the WHO has recommended the use of nirmatrelvir and ritonavir, and conditional recommendations for sotrovimab, remdesivir, and molnupiravir for high-risk patients with nonsevere COVID-19. For those with severe COVID-19, the WHO recommends corticosteroids with the addition of IL-6 receptor blockers or baricitinib, but advises against convalescent plasma, ivermectin, and hydroxychloroquine regardless of disease severity.

Though these drugs are common and inexpensive, the WHO said it cannot recommend the use of fluvoxamine or colchicine due to a lack of reliable data and "ongoing uncertainty about how the drugs produce an effect in the body, and evidence of little or no effect on survival and other important measures, such as risk of hospital admission and need for mechanical ventilation."

The decision about fluvoxamine was reached after reviewing three randomized control trials (RCTs) that involved a total of over 2,000 patients, and about colchicine based on seven RCTs involving over 16,000 patients.

Reference: WHO advises against use of two drugs for non-severe covid-19. BMJ. http://www.bmj.com/company/newsroom/who-advises-against-use-of-two-drugs-for-non.

MULTIPLE MYELOMA

Investigational drug's breakthrough therapy designation

The FDA has granted Breakthrough Therapy Designation to talquetamab for the treatment of adult patients with relapsed or refractory multiple myeloma, who have previously received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.

Talquetamab is an investigational, off-the-shelf, T-cell redirecting bispecific antibody targeting both GPRC5D, a novel drug target, on multiple myeloma cells and CD3 on T cells. It was previously granted PRIME (PRIority MEdicines) designation from the European Medicines Agency and an Orphan Drug Designation from the FDA.

The designation was supported by evidence from Phases 1 and 2 of the first-in-human dose-escalation MonumenTAL-1 study, presented at the 2022 European Hematology Association Annual Congress.

Patients treated with 405 mcg/kg of talquetamab (n = 30) experienced an overall response rate (ORR) of 70.0%, including a very good partial response (VGPR) rate or better of 56.7%. ORR among patients at the 800 mcg/kg dose was 63.6%, including a VGPR or better of 56.8%.

Commonly reported adverse effects (AEs) include cytokine release syndrome, skin-related events, and dysgeusia. The most common hematologic grade 3/4 AEs in the 405 mcg/kg and 800 mcg/kg groups were neutropenia, anemia, and lymphopenia. Common AEs included rashes, alanine aminotransferase increase, and decreased appetite.

References: Johnson & Johnson. Janssen announces U.S. FDA breakthrough therapy designation granted for talquetamab for the treatment of relapsed or refractory multiple myeloma. http://www.jnj.com/janssen-announces-u-s-fda-breakthrough-therapy-designation-gr.

Dose escalation study of talquetamab in participants with relapsed or refractory multiple myeloma - full-text view. https://clinicaltrials.gov/ct2/show/NCT03399799.

A study of talquetamab in participants with relapsed or refractory multiple myeloma - full-text view. https://clinicaltrials.gov/ct2/show/NCT04634552.

Virgil H. FDA grants breakthrough therapy designation to TALQUETAMAB for relapsed/refractory multiple myeloma. Cancer Network. 2022. http://www.cancernetwork.com/view/fda-grants-breakthrough-therapy-designation-to.

PSORIASIS

FDA approves roflumilast

The FDA has approved the New Drug Application for roflumilast (ZORYVE, Arcutis Biotherapeutics) for the treatment of plaque psoriasis, including intertriginous areas, in patients 12 years of age and older.

Roflumilast is a phosphodiesterase 4 inhibitor. Its approval is based upon the results from two Phase 3 trials, DERMIS-1 and DERMIS-2.

Significantly more patients treated with roflumilast achieved Investigator Global Assessment (IGA) success at Week 8 compared with vehicle (42% in DERMIS-1 and 37% in DERMIS-2 with ZORYVE compared with 6% in DERMIS-1 and 7% in DERMIS-2 with vehicle [P < .0001 in both studies]). IGA success was defined as clear or almost clear, plus a 2-grade or more IGA score improvement from baseline.

Roflumilast also improved the severity and impact of itch as early as week 2. Two-thirds of patients with a Worst Itch-Numerical Rating Score of 4 or higher at baseline achieved at least a 4-point reduction in itch at Week 8 with ZORYVE (67% versus 26% in DERMIS-1 and 69% versus 33% in DERMIS-2 at Week 8 [P < .0001]).

Roflumilast is contraindicated in patients with moderate to severe liver impairment.

The most common adverse reactions reported include diarrhea, headache, insomnia, application site pain, upper respiratory tract infections, and urinary tract infections.

Roflumilast systemic exposure may be increased and thus increase the risk of adverse reactions if administered with systemic CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously.

Similarly, coadministration with oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and may result in increased adverse reactions.

References: FDA approves Arcutis' zoryve(TM) (roflumilast) cream 0.3% for the treatment of plaque psoriasis in individuals age 12 and older. Arcutis Biotherapeutics. 2022. http://www.arcutis.com/fda-approves-arcutis-zoryve-roflumilast-cream-0-3-for-the.

ZORYVE Prescribing Information. 2022.

COVID-19

CDC recommends vaccines for young children

The CDC director Rochelle P. Walensky, MD, MPH, supported the Advisory Committee on Immunization Practices' recommendation that children ages 6 months to 5 years should receive the COVID-19 vaccine to ensure their safety. Parents and caregivers can now get their children vaccinated with the Pfizer-BioNTech or Moderna vaccines. This expands vaccine eligibility to nearly 20 million children in the US.

The CDC has confirmed that the COVID-19 vaccines have undergone some of the most intensive safety monitoring of any vaccine in US history. To ensure parents' and caregivers' peace of mind, they can sign up for v-safe, personalized health check-in via text messages and web surveys, where they have the option to share with the CDC how their child is feeling after receiving the vaccine.

Walensky believes that everyone should be safe and have access to the vaccine. "I encourage parents and caregivers with questions to talk to their doctor, nurse, or local pharmacist to learn more about the benefits of vaccinations and the importance of protecting their children by getting them vaccinated," she said in a press release.

Reference: Centers for Disease Control and Prevention. Coronavirus Disease 2019. 2022. http://www.cdc.gov/media/releases/2022/s0618-children-vaccine.html.

STATINS

Rosuvastatin and kidney disease

Rosuvastatin, compared with atorvastatin (both HMG-CoA reductase inhibitors), has been associated with an increased risk of hematuria, proteinuria, and kidney failure with replacement therapy (KFRT) in a paper published in The Journal of the American Society of Nephrology.

Rosuvastatin was associated with an 8% higher risk of hematuria, a 17% higher risk of proteinuria, and a 15% higher risk of developing KFRT such as dialysis or transplantation.

Researchers at the Johns Hopkins Bloomberg School of Public Health analyzed the deidentified electronic health record data of 152,101 new users of rosuvastatin and 795,799 new users of atorvastatin from 2011 to 2019.

The researchers estimated the inverse probability of treatment-weighted hazard ratios of hematuria, proteinuria, and KFRT associated with rosuvastatin. They also reported the initial rosuvastatin doses across the estimated glomerular filtration rate and evaluated for a dose effect on hematuria and proteinuria.

The researchers write that these results "suggest the need for greater care in prescribing and monitoring rosuvastatin, particularly in patients who receive high doses, or who have severe chronic kidney disease."

References: Shin J-I, Fine DM, Sang Y, et al. Association of rosuvastatin use with risk of hematuria and proteinuria. J Am Soc Nephrol. [e-pub July 19, 2022]

Real-World Data Links Rosuvastatin With Signs Of Kidney Damage. https://www.asn-online.org/about/press/releases/ASN_PR_20220719_JASN.Shin.FinalJ. July 19,2022.