Wednesday, June 19, 2024

New FDA approved antiviral shows promise for kidney transplant patients

The recently approved antiviral Letermovir for the treatment of cytomegalovirus infections (CMV) has also shown promise for kidney transplant patients, who are more susceptible to the virus, according to results of a phase-III clinical trial.

CMV is a common virus that infects people of all ages and spreads through body fluids. It usually remains dormant, causing no symptoms or a mild illness characterised by fever, sore throat, fatigue, or swollen glands.

But in people with impaired immune systems, such as transplant recipients, CMV can produce serious symptoms affecting the eyes, lungs, oesophagus, intestines, stomach, or liver.

Letermovir, developed by US drug major Merck (trade name, Prevymis), has shown similar efficacy to valganciclovir in preventing CMV disease in recipients of kidneys from CMV-positive donors.

Letermovir also causes less propensity to cause low counts of infection-fighting white blood cells, according to the results, published in the Journal of the American Medical Association (JAMA).

Letermovir was initially approved by the US Food and Drug Administration (FDA) in 2017, for preventing CMV illness in CMV-positive stem-cell transplant recipients. Now it has been extended for use among kidney transplant patients. Valganciclovir was approved in 2001.

Oral valganciclovir, given for 200 days after transplant, is standard care to prevent complications in high-risk kidney transplants from CMV-positive donors to CMV-negative recipients (about 20 per cent of all kidney recipients), but it causes immune suppression.

Valganciclovir can also lead to treatment stoppage, immunosuppressant dose reductions, and/or use of other drugs to stimulate the bone marrow to generate more neutrophil white blood cells. It also requires dose adjustments because of fluctuating kidney function after transplant and can lead to valganciclovir resistance.

Letermovir doesn’t require dose adjustment and isn’t tied to cross-resistance with other anti-CMV therapies. But, unlike valganciclovir, Letermovir has potential drug interactions and doesn’t act against herpes simplex virus or varicella zoster virus.

In the trial, an international team led by University of Washington researchers in Seattle compared antiviral effectiveness among 586 adult kidney transplant recipients who were randomly assigned to receive either Letermovir (480 milligrams) or valganciclovir (900 mg) for up to 200 days in 16 countries from May 2018 to April 2021, with follow-up until April 2022.

Letermovir (289 participants) was found noninferior to valganciclovir (297) in preventing CMV illness through one year after transplant (10.4 per cent vs 11.8 per cent) and had lower rates of leukopenia or neutropenia (low white blood-cell counts). Zero Letermovir recipients developed confirmed CMV illness through 28 weeks, compared with five (1.7 per cent) in the valganciclovir group.

The leukopenia or neutropenia rate by 28 weeks was lower in the Letermovir than the valganciclovir group (26 per cent vs 64 per cent).

Serious adverse-event rates were comparable in the two groups, including serious heart dysfunction (2.7 per cent in the Letermovir group vs 3.0 per cent in the valganciclovir group). Fewer drug-related and serious drug-related adverse events were reported with Letermovir than valganciclovir.

“Other considerations with valganciclovir include close monitoring of kidney function for dose adjustments and the need to convert to ganciclovir, with weight-based dosing, for intravenous administration,” the researchers said.

“In contrast, Letermovir is dosed independent of kidney function, and the dose and frequency are identical for oral and intravenous administration.”

However, Letermovir is 20 times more expensive, making it one of the most expensive routine post-transplant drugs, they said, calling for more trials.



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