Cost and availability of novel cell and gene therapies

Luca, Michele De; Cossu, Giulio

doi:10.15252/embr.202256661

Cited by 19 publications

(5 citation statements)

References 15 publications

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“… 54 Activation of vascular cells by PICSO can be considered an easy‐to‐use alternative to conceptual problem areas of cellular therapies and their translational aspect. 55 , 56 PICSO initiating mechanochemical signalling via pressure increase in cardiac veins might be an alternative to affect the secretome in heart failure patients, similar to paracrine effects recently described for cardiopoietic stem cells by Arell and colleagues. 57 If these results can be repeated in more extensive clinical trials, it may open a new avenue for heart failure therapy.…”

Section: Clinical Perspectivesmentioning

confidence: 65%

“…Cianflone reported on gene expression by miRNA, putting their negative gene regulation capacity as a primary modifier of cardiomyocyte regeneration in the adult heart into perspective 54 . Activation of vascular cells by PICSO can be considered an easy‐to‐use alternative to conceptual problem areas of cellular therapies and their translational aspect 55,56 . PICSO initiating mechanochemical signalling via pressure increase in cardiac veins might be an alternative to affect the secretome in heart failure patients, similar to paracrine effects recently described for cardiopoietic stem cells by Arell and colleagues 57 .…”

Section: Clinical Perspectivesmentioning

confidence: 84%

“…54 Activation of vascular cells by PICSO can be considered an easy-to-use alternative to conceptual problem areas of cellular therapies and their translational aspect. 55,56 PICSO initiating mechanochemical signalling via pressure increase in cardiac veins might be an alternative to…”

Section: Clinical Perspectivesmentioning

confidence: 99%

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Circulating microRNAs and cardiomyocyte proliferation in heart failure patients related to 10 years survival

Wagh,

Nguemo,

Kiseleva

et al. 2023

ESC Heart Failure

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AimsMechanochemical signalling drives organogenesis and is highly conserved in mammal evolution. Regaining recovery in myocardial jeopardy by inducing principles linking cardiovascular therapy and clinical outcome has been the dream of scientists for decades. Concepts involving embryonic pathways to regenerate adult failing hearts became popular in the early millennium. Since then, abundant data on stem cell research have been published, never reaching widespread application in heart failure therapy. Another conceptual access, using mechanotransduction in cardiac veins to limit myocardial decay, is pressure‐controlled intermittent coronary sinus occlusion (PICSO). Recently, we reported acute molecular signs and signals of PICSO activating regulatory miRNA and inducing cell proliferation mimicking cardiac development in adult failing hearts. According to a previously formulated hypothesis, ‘embryonic recall’, this study aimed to define molecular signals involved in endogenous heart repair during PICSO and study their relation to patient survival.Methods and resultsWe previously reported a study on the acute molecular effects of PICSO in an observational non‐randomized study. Eight out of the thirty‐two patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT) were treated with PICSO. Survival was monitored over 10 years, and coronary sinus blood samples were collected during intervention before and after 20 min and tested for miRNA signalling and proliferation when co‐cultured with cardiomyocytes. A numerically lower death rate post‐CRT and PICSO as compared with control CRT only, and a non‐significant reduction in all‐cause mortality risk of 42% was observed (37.5% vs. 54.0%, relative risk = 0.58, 95% confidence interval: 0.17–2.05; P = 0.402). Four miRNAs involved in cell cycle, proliferation, morphogenesis, embryonic development, and apoptosis significantly increased concomitantly in survivors and PICSO compared with a decrease in non‐survivors (hsa‐miR Let7b, P < 0.01; hsa‐miR‐ 421, P < 0.006; hsa‐miR 363‐3p, P < 0.03 and hsa‐miR 19b‐3p P < 0.01). In contrast, three miRNAs involved in proliferation and survival, determining cell fate, and recycling endosomes decreased in survivors and PICSO (hsa miR 101‐3p, P < 0.03; hsa‐miR 25‐3p, P < 002; hsa‐miR 30d‐5p P < 0.04). In vitro cellular proliferation increased in survivors and lowered in non‐survivors showing a pattern distinction, discriminating longevity according to up to 10‐year survival in heart failure patients.ConclusionsThis study proposes that generating regenerative signals observed during PICSO intervention relate to patient outcomes. Morphogenetic pathways induced by periods of flow reversal in cardiac veins in a domino‐like pattern transform embryonic into regenerative signals. Studies supporting the conversion of mechanochemical signals into regenerative molecules during PICSO are warranted to substantiate predictive power on patient longevity, opening new therapeutic avenues in otherwise untreatable heart failure.

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Section: Clinical Perspectivesmentioning

confidence: 65%

Section: Clinical Perspectivesmentioning

confidence: 84%

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Circulating microRNAs and cardiomyocyte proliferation in heart failure patients related to 10 years survival

Wagh,

Nguemo,

Kiseleva

et al. 2023

ESC Heart Failure

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“…The remaining four (23.5%) products maintained their approval in the US but not in the EU. Betibeglogene (Tecartus) and elivaldogene (Skysona) were initially approved in the EU in 2019 and 2021, respectively, but the products were withdrawn from the EU market for commercial reasons [26,27]. Subsequently, they obtained approval and remained marketed in the US.…”

Section: Resultsmentioning

confidence: 99%

Characterizing Gene Therapy Medicinal Products Post-Marketing Safety Reports based on WHO Pharmacovigilance Database, VigiBase

Lim,

Paek,

Shin

2024

Preprint

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Background Safety assessments of gene therapy medicinal products (GTMPs) require comprehensive data collection from a variety of sources to ensure thorough evaluation. This study aimed to analyze the characteristics of adverse event (AE) reports for GTMPs, dividing them into Solicited Reports (SRs) and Unsolicited Reports (USRs), and to provide insights for developing effective pharmacovigilance strategies customized for GTMPs.Methods Individual case safety reports (ICSRs) collected from GTMPs were retrieved using VigiBase. We identified GTMPs approved by the United States Food and Drug Administration (US FDA) and/or European Medicines Agency (EMA) by December 31, 2022, and maintained their approval status as of July 28, 2023. Descriptive statistics were used to summarize the ICSRs’ characteristics. The reported AEs were classified into System Organ Classes (SOCs) and Preferred Terms (PTs).Results A total of 12,180 ICSRs for 13 GTMPs were retrieved from VigiBase. Of these, 27.6% were SR and 72.4% USR. As the number of ICSRs increased, the proportion of USR tended to increase. Compared to the SR, consumer reports were much less common in the USR. The majority of the reported events were serious in both groups. In the drug-AE pairs, cytokine release syndrome and pyrexia were the most commonly reported in both the SR and USR. Meanwhile the most frequently reported SOCs were “Investigations” in SR and “Nervous system disorders” in USR, respectively.Conclusions Our study highlights the need for robust pharmacovigilance measures customized for GTMPs. The continued refinement of pharmacovigilance strategies customized for GTMPs is essential to ensure their safe and effective use.

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“…As a result, some efficacious and approved products, such as Skysona for adrenoleukodystrophy and Zynteglo for beta-thalassemia, have been withdrawn from the European market, leaving patients who might have benefited from these life-saving therapies without access to them. Secondly, companies may decide to drop an approved ATMP, even when it is approved and when a reimbursement policy has been negotiated, simply due to insufficient economic return [ 12 ]. This is particularly true for rare diseases where the very low number of patients poses significant challenges.…”

mentioning

confidence: 99%

The Relevance of Advanced Therapy Medicinal Products in the Field of Transplantation and the Need for Academic Research Access: Overcoming Bottlenecks and Claiming a New Time

Piemonti,

Scholz,

de Jongh

et al. 2023

Transpl Int

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The field of transplantation has witnessed the emergence of Advanced Therapy Medicinal Products (ATMPs) as highly promising solutions to address the challenges associated with organ and tissue transplantation. ATMPs encompass gene therapy, cell therapy, and tissue-engineered products, hold immense potential for breakthroughs in overcoming the obstacles of rejection and the limited availability of donor organs. However, the development and academic research access to ATMPs face significant bottlenecks that hinder progress. This opinion paper emphasizes the importance of addressing bottlenecks in the development and academic research access to ATMPs by implementing several key strategies. These include the establishment of streamlined regulatory processes, securing increased funding for ATMP research, fostering collaborations and partnerships, setting up centralized ATMP facilities, and actively engaging with patient groups. Advocacy at the policy level is essential to provide support for the development and accessibility of ATMPs, thereby driving advancements in transplantation and enhancing patient outcomes. By adopting these strategies, the field of transplantation can pave the way for the introduction of innovative and efficacious ATMP therapies, while simultaneously fostering a nurturing environment for academic research.

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Cost and availability of novel cell and gene therapies

Abstract: Advanced gene and cellular therapies risk a second “valley of death” due to their high costs and low patient population. As these are life‐saving therapies, measures are urgently needed to prevent their withdrawal from the market.

Cited by 19 publications

References 15 publications

Circulating microRNAs and cardiomyocyte proliferation in heart failure patients related to 10 years survival

Circulating microRNAs and cardiomyocyte proliferation in heart failure patients related to 10 years survival

Characterizing Gene Therapy Medicinal Products Post-Marketing Safety Reports based on WHO Pharmacovigilance Database, VigiBase

The Relevance of Advanced Therapy Medicinal Products in the Field of Transplantation and the Need for Academic Research Access: Overcoming Bottlenecks and Claiming a New Time

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