by
Gabrielle O’Sullivan PhD MPH (Hons) 1
1Executive Officer, Royal Prince Alfred Hospital Institutional Biosafety Committee,
Royal Prince Alfred Hospital, Australia
.
AUSTRALIAN AND NEW ZEALAND REGULATORY UPDATES
Medsafe
Medsafe has updated its Guidelines on the Regulation of Therapeutic Products in New Zealand in relation to Changed Medicine Notifications and Non-Notifiable Changes (V1.2, Sept 23), Manufacture of Medicines (V5.2, Sept 2023), and Advertising Of Therapeutic Products (V2.1, Oct 2023) [1]; and is consulting on proposed updates to its Pharmacovigilance Guideline [2].
TGA
The TGA has launched a new search feature in its Adverse Event Management System (AEMS) portal, whereby sponsors can access adverse event reports about their medicines and biologicals, and download de-identified Public Case Detail (PCD) and Case Line Listing (CLL) reports for inclusion into their own pharmacovigilance systems [3, 4].
More than 307,000 units of unlawfully imported medicines and medical devices with an estimated value of over $2 million were seized in a joint operation by the TGA and Australian Border Force (ABF). The products included (among others) prescription medications, 36kg of border-controlled drugs, performance and image enhancing drugs, narcotics, benzodiazepines, and counterfeit, falsified and substandard medicines. Over 370 Australian-hosted online advertisements unlawfully promoting therapeutic goods were removed [5]. The operation was part of INTERPOL’s Operation Pangea XVI, a global operation targeting the trade of illicit and counterfeit therapeutic goods worldwide [6].
INTERNATIONAL REGULATORY UPDATES RELEVANT TO AUSTRALIA & NEW ZEALAND
FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies
Please see the US FDA website for details [7].
The MHRA has authorised CASGEVY™ (exagamglogene autotemcel [exa-cel]) gene therapy for sickle-cell disease and transfusion-dependent β-thalassemia
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has granted conditional marketing authorization for CASGEVY™ (exagamglogene autotemcel [exa-cel]), a CRISPR/Cas9 gene-edited therapy, for the treatment of sickle cell disease and transfusion-dependent beta thalassemia. The authorisation was granted on 15 November 2023 to Vertex Pharmaceuticals (Europe) Ltd and CRISPR Therapeutics. This is the first regulatory authorization of a CRISPR-based gene-editing therapy in the world [8-10]. FDA decision is expected on 8 December 2023 [11].
Amendments to the 2024 US spending Bill for the Department of Health and Human Services (HHS) that could result in a ban on Gain Of Function (GOF) research, reduce research funding and diversity and limit research topics
On Tuesday 14 November 2023, the U.S. House of Representatives approved a provision in amendments to the 2024 House spending Bill for the Department of Health and Human Services (HHS) (the National Institutes of Health parent agency) that “None of the funds made available by this Act may be used, either directly or indirectly, to conduct or support any gain-of-function research involving a potential pandemic pathogen.” It is hoped that the Democratic-controlled Senate will not allow the measure to become law. Another amendment proposes to reduce NIH’s current $47.4 billion budget by $6 billion, and there are provisions in an accompanying report that would curb diversity efforts and ban NIH-funded research on topics such as fetal tissue research and gender-affirming care [12-14].
Telethon Foundation in Italy to take over production of Strimvelis
On the 12 September 2023, it was announced that the European manufacturing and distribution rights for Strimvelis, a gene therapy approved by the EMA in 2016 for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID), have been fully transferred to Fondazione Telethon, a non-profit organization, from its former holder, Orchard Therapeutics, which previously announced it would discontinue investment in and seek strategic alternatives for its programs in rare primary immune deficiencies, including Strimvelis. Strimvelis is a gene therapy for ADA-SCID which is composed of autologous CD34+ enriched cell fraction that contains CD34+ cells transduced with retroviral vector encoding the human ADA cDNA sequence. The marketing authorization transfer was approved on July 17th, 2023, by the European Commission following a positive opinion from the European Medicines Agency (EMA). Fondazione Telethon is the first non-profit organization to take on the commercialization of a gene therapy. [15] This development is of interest to other countries as it has potential to open new ways of providing access to gene therapies for rare diseases.
Genetically modified pig heart transplanted into a human
On 22 September 2023, it was announced that the world’s second patient had undergone xenotransplantation, at the University of Maryland Medical Center (UMMC), with a genetically modified pig heart. The FDA granted emergency approval for the surgery on 15 September via its single-patient investigational new drug (IND) “compassionate use” pathway. The first genetically modified cardiac xenotransplant was performed in 2022. [16,17]
Dark Horse Consulting (DHC) has opened an APAC branch
Dark Horse Consulting (a premium CGT consultancy) has opened a new APAC office with John Ng as General Manager. Most recently, John served as Chief Technical Officer of Tessa Therapeutics, a clinical-stage biotechnology company based in Singapore that was developing a portfolio of autologous and allogeneic cell therapy assets. The company grew from 30 employees to more than 200 during his seven-year tenure [18].
REFERENCES
1. Medsafe, Guidelines on the Regulation of Therapeutic Products in New Zealand, https://www.medsafe.govt.nz/regulatory/current-guidelines.asp
2. Medsafe, Proposed updates to the Guideline on the Regulation of Therapeutic Products in New Zealand: Pharmacovigilance, https://consult.health.govt.nz/medsafe/pharmacovigilance-guidelines-update/, Opened 2 Nov 2023, Closes 14 Dec 2023
3. TGA, New medicine adverse event search for sponsors, https://www.tga.gov.au/news/news/new-medicine-adverse-event-search-sponsors, Published 20 November 2023
4. TGA, Adverse Event Reporting, https://aems.tga.gov.au/
5. TGA, Joint operation seizes $2 million worth of unlawfully imported therapeutic goods, https://www.tga.gov.au/news/media-releases/joint-operation-seizes-2-million-worth-unlawfully-imported-therapeutic-goods, Published 16 November 2023
6. INTERPOL, Global illicit medicines targeted by INTERPOL operation, Taking down the transnational crime groups threatening consumer safety, https://www.interpol.int/en/News-and-Events/News/2023/Global-illicit-medicines-targeted-by-INTERPOL-operation, Published 31 October 2023
7. FDA Investigating Serious Risk of T-cell Malignancy Following BCMA-Directed or CD19-Directed Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies, https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-investigating-serious-risk-t-cell-malignancy-following-bcma-directed-or-cd19-directed-autologous?utm_medium=email&utm_source=govdelivery, published 28 November 2023 (information courtesy of K Kime)
8. MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia, https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia, Published 16 November 2023
9. Vertex and CRISPR Therapeutics Announce Authorization of the First CRISPR/Cas9 Gene-Edited Therapy, CASGEVY™ (exagamglogene autotemcel), by the United Kingdom MHRA for the Treatment of Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia, BOSTON & ZUG, Switzerland--(BUSINESS WIRE), Published Nov. 16, 2023
https://crisprtx.com/about-us/press-releases-and-presentations/vertex-and-crispr-therapeutics-announce-authorization-of-the-first-crispr-cas9-gene-edited-therapy-casgevy-exagamglogene-autotemcel-by-the-united-kingdom-mhra-for-the-treatment-of-sickle-cell-disease-and-transfusi
View source version on businesswire.com: https://www.businesswire.com/news/home/20231115290500/en/
10. UK first to approve CRISPR treatment for diseases: what you need to know, https://www.nature.com/articles/d41586-023-03590-6, published 23 November 2023
11. C Newman, Biopharma Dive, FDA sets decision dates for Vertex, CRISPR gene editing drug, https://www.biopharmadive.com/news/vertex-crispr-priority-review-sickle-cell-gene-editing/652581/, published 9 June 2023
12. J Kaiser, House approves ban on gain-of-function pathogen research, Science, https://www.science.org/content/article/house-approves-ban-gain-function-pathogen-research, Published 15 November 2023
13. USA Congress, 118th Congress (2023-2024), H.R.5894 - Making appropriations for the Departments of Labor, Health and Human Services, and Education, and related agencies for the fiscal year ending September 30, 2024, and for other purposes, https://www.congress.gov/bill/118th-congress/house-bill/5894
14. S Owermohle, House moves to limit so-called gain-of-function research, STAT, https://www.statnews.com/2023/11/15/gain-of-function-research-limit/, Published 15 November 2023
15. Fondazione Telethon, Fondazione Telethon and Orchard Therapeutics complete transfer of marketing authorization of Strimvelis for ADA-SCID in Europe, https://www.telethon.it/en/stories-and-news/news/from-telethon-foundation/fondazione-telethon-orchard-therapeutics-complete-transfer-marketing-authorization-strimvelis-for-ada-scid-europe/, Published 12 September 2023
16. M Molteni, Genetically altered pig heart transplanted into a human for the second time, https://www.statnews.com/2023/09/22/pig-heart-transplant-university-of-maryland/, published 22 September 2023
17. Genetically-Modified Pig Heart Is Xenotransplanted into a Second Patient, https://www.genengnews.com/topics/translational-medicine/genetically-modified-pig-heart-is-xenotransplanted-into-a-second-patient/, published 25 September 2023
18. Dark Horse Consulting Group Announces Launching of DHC Asia Pacific, Hiring of John Ng as General Manager, https://www.globenewswire.com/news-release/2023/11/13/2779505/0/en/Dark-Horse-Consulting-Group-Announces-Launching-of-DHC-Asia-Pacific-Hiring-of-John-Ng-as-General-Manager.html, Published 13 November 2023 (information courtesy of K Kime)
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