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CHMP recommends conditional marketing authorisation for teclistamab monotherapy
The Committee for Medicinal Products for Human Use ( CHMP ) has recommended conditional marketing authorisation for Tecvayli ® ( teclistamab ).
The CHMP recommendation is based on positive results from the multicohort , open-label , Phase I / II MajesTEC-1 study ( NCT03145181 and NCT04557098 ), evaluating the safety and efficacy of teclistamab in adults with relapsed and refractory multiple myeloma ( RRMM ).
Teclistamab is an off-the-shelf , T-cell redirecting bispecific antibody . It targets both B-cell maturation antigen , a marker found on multiple myeloma cells , and CD3 , on T-cells . It is recommended as monotherapy for adult patients with RRMM who have received at least three prior therapies , including an immunomodulatory agent , a proteasome inhibitor , and an anti-CD38 antibody and have demonstrated disease progression on the last therapy .
In December 2021 , the EMA granted accelerated assessment for teclistamab . Accelerated assessment reduces the timeframe for the CHMP to review a marketing authorisation application and is granted when a medicinal product is of major interest for public health and therapeutic innovation .
The latest findings from the study were presented at the American Society of Clinical Oncology ( ASCO ) 2022 Annual Meeting and published in The New England Journal of Medicine . 1 Teclistamab resulted in deep and durable responses in patients with triple-class exposed multiple myeloma ( n = 165 ). With a median follow-up of approximately 14 months ( 14.1 ), the overall response rate was 63 % ( 95 % CI : 55.2 – 70.4 ), with 39.4 % having a complete response ( CR ) or better . Almost half ( 46 %) of patients who achieved a CR or better were minimal residual disease-negative .
Adverse events ( AEs ) were consistent with this patient population and toxicities consistent with T-cell redirection were mostly Grade 1 / 2 . The most common AEs were cytokine release syndrome and neutropenia . Infections were frequent ( 76.4 %; 44.8 % Grade 3 or 4 ). The overall incidence of neurotoxic events was low and five patients had immune effector cell-associated neurotoxicity syndrome . There were five treatment-related deaths , and dose reductions and discontinuations due to AEs were infrequent .
Citation Moreau P et al . Teclistamab in relapsed or refractory multiple myeloma . N Engl J Med 2022 ; June 5 : DOI 10.1056 / NEJMoa2203478 .
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Should the serotonin theory of depression be abandoned ?
The serotonin theory ( ST ) of depression should no longer be promoted as there is a distinct lack of credible supportive evidence , according to the findings of a recent umbrella review by an international group based at the Division of Psychiatry , UCL , London , UK .
The selective serotonin re-uptake inhibitors ( SSRIs ) are a class of antidepressant drugs that include fluoxetine , citalopram and sertraline and commonly used in the treatment of depression . The mode of action of SSRIs is described as inhibition of the re-uptake of serotonin , thereby increasing activity of the neurotransmitter . In other words , the concept of depression is predicated on the ST , i . e ., low levels of the transmitter lead to depression although this premise has been challenged in recent years . Nevertheless , the concept of a chemical imbalance as an underlying cause of depression is a widespread belief among the general public and , it seems among healthcare professionals . In a survey of 66 UK general practitioners , 23 % strongly agreed and 54 % agreed that depression is caused by a chemical imbalance . Despite belief in the ST of depression , to date , no comprehensive review has synthesised the available evidence to either confirm or refute the theory .
For the present umbrella review , researchers examined the available literature to try and establish if there was credible support for the ST . In doing so , they focused on several specific areas that could provide evidence to support the theory . They initially examined whether there were lower levels of both serotonin and 5-hydroxyindoleacetic acid ( 5-HIAA ), its active metabolite , in body fluids among those with depression . Secondly , if there were alterations in the level of serotonin receptors . Thirdly , if levels of serotonin transporter ( SERT ) protein , which remove the transmitter from the synapse , were elevated in depression . Fourthly , whether tryptophan depletion ( which also lowers serotonin levels ) could induce depression and finally , the researchers looked at if there were elevated levels of the SERT gene in depressed patients . The researchers identified a total of 17 eligible studies for inclusion in their umbrella review .
Two meta-analyses with a total of 19 studies failed to provide evidence of an association between 5-HIAA levels and depression .
The team then focused on levels of the 5-HT1A receptor , an auto-receptor that inhibits the release of serotonin presynaptically . If depression is due to lowered levels of serotonin , the activity of this receptor should be enhanced although
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