Free special edition 2023

MARKETING AUTHORISATIONS

NEW SUBSTANCE

EDITORS’ OPINION

Luspatercept (REBLOZYL°) in anaemia associated with myelodysplastic syndrome

New is not necessarily better

Poor-quality sleep is a common complaint, and can be very troublesome or distressing for patients and those around them. Patients in this situation are sometimes offered pharmacological treatment. Benzo- diazepines and benzodiazepine-like drugs have been used to treat insomnia for decades and, over the years, it has become clear that their efficacy is modest at best and often short lived. And they have adverse effects that are sometimes serious. This knowledge, accrued over time, contributes to the decision of whether or not to use a benzodiazepine, which, in the absence of a better alternative, is sometimes a reasonable option. It has been years since a hypnotic belonging to a new pharmacological class has been grant ed marketing authorisation in the European Union for the treatment of insomnia. Hopes were therefore high among certain patients and health professionals when daridorexant (Quviviq°) was authorised in Europe. Unfortunately, after a rigorous analysis of the available evaluation data, Prescrire can only conclude that daridorexant is yet another new drug that offers “Nothing new” for patients (see page 6 ). In trials conducted in highly selected patients, daridorexant had modest efficacy, enabling patients to get a few more minutes of sleep per night on aver age compared to placebo. This is unlikely to transform the lives of patients or the people around them, even in patients who experience severe insomnia every night. And what about the risks of depression, suicide, narcolepsy, cataplexy, dependence and other rare but potentially serious adverse effects? They remain unclear as of 2023, but could well eventually be confirmed, after years on the market. When a drug appears to have limited efficacy, uncertainties due to the lack of long-term data weigh heavily on its harm-benefit balance. A drug that is “new” is not necessarily a thera peutic advance: recognising this distinction is important to the provision of high-quality care.

NOT ACCEPTABLE For patients with anaemia associated withmyelodysplastic syndrome,when an epoetin is no longer an option, lus patercept has beenevaluated ina sin

gle placebo-controlled trial. A 5q deletion was not present intheneoplasticcells inanyofthesepatients. In this trial, a minority of patients from the luspater cept groupwere able todispensewithtransfusions in the short term compared to those in the placebo group. However, there was no reduction in the main symptoms ofanaemia, andthe level ofevidencepro videdbythesedata is lowduetomethodological flaws in the trial. Luspatercept has numerous adverse effects, including: fatigue, dyspnoea, infections, gastro intestinal disorders, hypersensitivity reactions, kidney damage (sometimes fatal), liverdamage (sometimes severe), tachyarrhythmias, andpossibly cancer inthe longterm. Redbloodcell transfusions, or lenalidomide inpatientswith5qdeletion, arebetteroptions, despite their limitations.

REBLOZYL° - luspatercept powder for solution for subcutaneous injection • 25mg or 75mg of luspatercept per vial Bristol-Myers Squibb ■ Erythroidmaturation agent

■ Indication : “ transfusion-dependent anaemia due to very low, low and intermediate-risk myelodysplastic syndromes with ring sidero blasts [in adults] who had an unsatisfactory response to or are ineli gible for erythropoietin-based therapy. ” [EU centralised procedure – orphan drug] ■ Dosage : initial dose of 1 mg/kg every 3 weeks, adjusted there after according to haemoglobin level, transfusion requirements and adverse effects, with in general an ongoing dose between 0.8 and 1.75mg/kg every 3weeks.

©Prescrire

▶ Translated from Rev Prescrire November 2022 Volume 42 N° 469 • Full French version: 4 pages Prescrire Int • February 2023

©Prescrire

Prescrire Int • July/August 2023

Prescrire International Special Edition 2023 • Page 7