# Expediting marketing authorization pathways for patients' access to advanced therapies

Valentin Roby, Luc-Sylvain Gilbert, Valentin Brunel, Auxane Delage, Aurélie Mahalatchimy

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Valentin Roby, Luc-Sylvain Gilbert, Valentin Brunel, Auxane Delage, Aurélie Mahalatchimy. Expediting marketing authorization pathways for patients’ access to advanced therapies. European Association of Health Law 2024, Sep 2024, Warsaw, Poland. halshs-04842656

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Submitted on 17 Dec 2024

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Distributed under a Creative Commons Attribution 4.0 International License
# The expediting marketing authorisation pathways for patients' access to advanced therapies

Valentin Roby<fnref n="1" />, Luc-Sylvain Gilbert², Valentin Brunel³, Auxane Delage⁴, Aurélie Mahalatchimy⁵

**Acknowledgments:** This work has been supported by the European Union's Horizon 2020 EuroGCT project (GA No 965241) and by ANR-funded I-BioLex project (ANR-20-CE26-0007-01).

## BACKGROUND & AIM

Medicinal products based on genes, cells and tissues of human or animal origin are being developed to treat severe diseases that conventional treatments have failed to treat or that have no available and satisfactory treatments, such as rare, genetic, or neurodegenerative diseases.

The risks they raise as innovative and complex medicines but also the therapeutic promises they offer have led to their specific regulation as Advanced Therapy Medicinal Products (ATMPs) in the European Union (EU). ATMPs include 4 legal sub-categories : Cell-therapy medicinal products (CTMP), Gene therapy medicinal products (GTMP), Tissue engineered products (TEP) and Combined (Comb.) ATMPs. They are especially submitted to the centralised procedure of Marketing Authorisation (MA) issued by the European Commission. This procedure aims not only to ensure high quality, safety and efficacy for ATMPs with a positive risk-benefit balance to be commercialised, but also a wide access to these medicines for EU patients. To date, 26 ATMPs have been granted a MA in the EU. Nevertheless, this procedure alone is not always sufficient to allow the commercialisation of ATMPs, and many of them require expediting pathways or regulatory support schemes for innovative medicines to be commercialised.

What are these expediting pathways and how much have they been used for ATMPs ?

## Overview of the 26 authorised ATMPs in the EU

<table><caption>List of ATMPs</caption><thead><tr><th>Name</th><th>Type</th><th>Domain</th><th>MA Year</th><th>Current status</th></tr></thead><tbody><tr><td>ChondroCelect</td><td>TEP</td><td>Orthopaedic</td><td>2009</td><td>Withdrawn, 29/07/2016</td></tr><tr><td>Glybera</td><td>GTMP</td><td>Gastrology</td><td>2012</td><td>Withdrawn, 28/10/2017</td></tr><tr><td>MACI</td><td>Comb. TEP</td><td>Orthopaedic</td><td>2013</td><td>Withdrawn, 01/07/2018</td></tr><tr><td>Provenge</td><td>CTMP</td><td>Oncology</td><td>2013</td><td>Withdrawn, 06/05/2015</td></tr><tr><td>Holoclar</td><td>TEP</td><td>Ophthalmology</td><td>2015</td><td>Positive</td></tr><tr><td>Imlygic</td><td>GTMP</td><td>Oncology</td><td>2015</td><td>Positive</td></tr><tr><td>Strimvelis</td><td>GTMP</td><td>Immunology</td><td>2016</td><td>Positive</td></tr><tr><td>Zalmoxis</td><td>CTMP</td><td>Graft. vs. host</td><td>2016</td><td>Withdrawn, 09/10/2019</td></tr><tr><td>Spherox</td><td>TEP</td><td>Orthopaedic</td><td>2017</td><td>Positive</td></tr><tr><td>Alofisel</td><td>CTMP</td><td>Gastrology</td><td>2018</td><td>Positive</td></tr><tr><td>Yescarta</td><td>GTMP</td><td>Immunocellular cancer</td><td>2018</td><td>Positive</td></tr><tr><td>Kymriah</td><td>GTMP</td><td>Immunocellular cancer</td><td>2018</td><td>Positive</td></tr><tr><td>Luxturna</td><td>GTMP</td><td>Ophthalmology</td><td>2018</td><td>Positive</td></tr><tr><td>Zynteglo</td><td>GTMP</td><td>Beta-Thalassemia</td><td>2019</td><td>Withdrawn, 24/03/2022</td></tr><tr><td>Zolgensma</td><td>GTMP</td><td>Muscular Atrophy</td><td>2020</td><td>Positive</td></tr><tr><td>Libmeldy</td><td>GTMP</td><td>Metachromatic Leukodystrophy</td><td>2020</td><td>Positive</td></tr><tr><td>Tecartus</td><td>GTMP</td><td>Lymphoma, Mantle-Cell</td><td>2020</td><td>Positive</td></tr><tr><td>Skysona</td><td>GTMP</td><td>Cerebral adreno leuko-dystrophy</td><td>2021</td><td>Withdrawn, 18/11/2021</td></tr><tr><td>Abecma</td><td>GTMP</td><td>Multiple Myeloma cancer of the bone marrow</td><td>2021</td><td>Positive</td></tr><tr><td>Breyanzi</td><td>GTMP</td><td>Blood cancer</td><td>2022</td><td>Positive</td></tr><tr><td>Carvykti</td><td>GTMP</td><td>Multiple Myeloma cancer of the bone marrow</td><td>2022</td><td>Positive</td></tr><tr><td>Upstaza</td><td>GTMP</td><td>Amino Acid Metabolism, Inborn Errors</td><td>2022</td><td>Positive</td></tr><tr><td>Roctavian</td><td>GTMP</td><td>Haemophilia A</td><td>2022</td><td>Positive</td></tr><tr><td>Ebvallo</td><td>CTMP</td><td>Lymphoprofilerative Disorders</td><td>2022</td><td>Positive</td></tr><tr><td>Hemgenix</td><td>GTMP</td><td>Haemophilia B</td><td>2023</td><td>Positive</td></tr><tr><td>Casgevy</td><td>GTMP</td><td>Beta-Thalassemia and sickle cell disease</td><td>2024</td><td>Positive</td></tr></tbody></table>

<figure><img src="image_2.png" /><figcaption>Fig. 1: Authorised ATMPs by legal sub-categories</figcaption></figure>

<figure><img src="image_3.png" /><figcaption>Fig. 2: Country of ATMPs MA holders</figcaption></figure>

<figure><img src="image_4.png" /></figure>

<figure><img src="image_5.png" /><figcaption>Fig. 5: PRIME among the 26 authorised ATMPs</figcaption></figure>

## RESULTS

* Clear increase in approvals from 2018 in various medical domains

* Most approved ATMPs are gene therapy medicinal products

* NL, where is established the European Medicines Agency from Brexit, and IE are the countries of most of MA holders among the authorised ATMPs

* Half of authorised ATMPs benefited from expediting pathways or regulatory support schemes for innovative medicines

* BUT MA withdrawn or not renewed for 7 ATMPs out of 26 authorized ATMPs

## DISCUSSION/CONCLUSION

Even if the EU supports and fosters ATMPs' research, development, and access to market with regulatory tools, patients access to effective and affordable ATMP is limited by the high average cost per patient, the withdrawal of authorised ATMPs from MA holder mostly for commercial reasons, and the differences between healthcare systems and reimbursement strategies of the different Member States.

Although the standard procedure and the expediting MA pathways provide the widest commercialisation of ATMPs in Europe, patients' access to ATMPs is dependent on MA granting and on the MA holder strategy to make the product available in Europe. The latter is linked to the agreement(s) on pricing and reimbursement to provide affordable ATMPs as well as an acceptable financial benefit, including return on investment, for the MA holder.

Patients can also access ATMPs, thanks to other pathways, alternative to MA and possible under strict conditions only. However, depending on how these other pathways can be used according to the applicable national heterogenous rules (e.g., hospital exemption), they could also lead to unfair competition regarding the high requirements for MA granting.

<footnote n="1">¹ Research Engineer in law, EuroGCT and I-BioLex research projects, Law Faculty, Aix Marseille Univ, CNRS, DICE, CERIC, Aix-en-Provence, France; ² EuroGCT Information Officer on ELSI, Research Engineer in law, Law Faculty, Aix Marseille Univ, CNRS, DICE, CERIC, Aix-en-Provence, France; ³ Study Engineer at the French National Centre for Scientific Research (IE CNRS), Law Faculty, Aix Marseille Univ, CNRS, DICE, CERIC, Aix-en-Provence, France; ⁴ EuroGCT Information Officer on Ethical, Legal & Societal issues (ELSI), Research Engineer and PhD student in law, Law Faculty, Aix Marseille Univ, CNRS, DICE, CERIC, Aix-en-Provence, France; ⁵ CNRS Permanent Researcher in law (CR), EuroGCT Deputy coordinator and WP4 leader, I-BioLex PI, Law Faculty, Aix Marseille Univ, CNRS, DICE, CERIC, Aix-en-Provence, France.</footnote>