Gabrielle O’Sullivan PhD MPH1 and Giulia Giunti PhD2
1Executive Officer, Royal Prince Alfred Hospital Institutional Biosafety Committee, Royal Prince Alfred Hospital, Australia
2Quality Manager, Malaghan Institute of Medical Research, Wellington, New Zealand
Hemgenix
CSL Behring GmbH received EU Conditional Marketing Approval on 20 February 2023 for Hemgenix (etranacogene dezaparvovec) for the treatment of adults with severe and moderately severe haemophilia B who have not developed inhibitors against factor IX [1 - 3].
Hemigenix is an adeno-associated viral (AAV5) vector-based gene therapy that encodes factor IX. Patients with haemophilia B have mutations (changes) in a gene which the body needs to make the clotting protein Factor IX, resulting in either a partial or complete lack of its activity [1]
Hemigenix received FDA BLA approval on 22 November 2022 [4, 5].
As of 22 March 2023, Hemgenix has not yet been approved by the TGA, but it was granted orphan designation by the TGA in August 2022 [6]. CSL Behring Australia Pty Ltd plans to seek TGA registration in due course.
Carvykti
On 27 January 2023, Janssen announced that the Phase 3 CARTITUDE-4 study evaluating Carvykti® (ciltacabtagene autoleucel; cilta-cel) versus pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) for the treatment of patients with relapsed and lenalidomide-refractory multiple myeloma met its primary endpoint of significant improvement in progression-free survival (PFS) at the first pre-specified interim analysis. As a result of meeting the primary endpoint, the Independent Data Monitoring Committee recommended the unblinding of the study. Janssen plans to present the data from the CARTITUDE-4 study at a future medical meeting. [7]
Carvykti® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR positive T-cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. [7]
Carvykti® has received regulatory approvals from the FDA, EMA and Japan's Ministry of Health, Labour and Welfare (MHLW) in 2022, but not yet from the Australian TGA.
Janssen has decided to cease seeking approval of the therapy from the UK National Institute of Health and Care Excellence (NICE). NICE assesses applications for funding by the UK National Health Service (NHS). Janssen’s decision is thought to be related to production issues affecting the ability to meet demand (rather than safety or efficacy issues) [8].
The Australian Medical Services Advisory Committee (MSAC) did not support public funding for Carvykti® at its consideration on 28-29 July 2022. Janssen Australia did not agree with MSAC’s consideration that the evidence base is insufficient for determining the comparative safety and effectiveness, and Janssen noted that single arm clinical trials have been the accepted evidence base for all previously approved CAR-T therapies considered by MSAC [9].
Being a genetically modified cell therapy, in New Zealand Carvykti® required approval by the Environmental Protection Authority (EPA) which it received in August 2022 [10]. In Australia, it would not require approval by the Office of the Gene Technology Regulator (OGTR) because it would be classed as an exempt GMO dealing if it meets the criteria for this.
Third International Summit on Human Genome Editing
Patrick Foong (ANZ ISCT member) attended the Third International Summit on Human Genome Editing from 6-8 March 2023 [11] and has published two articles on it [12A, 12B].
National Clinical Trials Governance Framework
In March 2023, the Australian Council on Healthcare Standards (ACHS) commenced assessing health service organisations that conduct clinical trials against the new National Clinical Trials Governance Framework which was developed by the Australian Commission on Safety and Quality in Health Care (ACSQHC, the Commission). This is the first step towards a nationally consistent approach to the accreditation of health services for the conduct of clinical trials.
The Governance Framework aims to ensure that clinical trials are conducted in a safe environment and in a high-quality manner for improved health outcomes for patients and the community. The Governance Framework is based on the Commission’s existing National Safety and Quality Health Service (NSQHS) Standards, in particular, Standard 1: Clinical Governance and Standard 2: Partnering with Consumers. [13, 14]
Reconsiderations of privacy legislation
Australia is reconsidering its privacy legislation with a report (the Privacy Act Review Report 2022) released in early February 2023 detailing the Australian Government’s review of the Privacy Act 1988 (the Act). The Attorney-General’s Department has been seeking feedback to inform the Australian Government response to the Report. Feedback was due 31 March 2023. [15, 16].
The UK has also proposed reform of its General Data Protection Regulation (GDPR) and introduced a Bill into the House of Commons on 8 March 2023 on regulating the processing of information relating to individuals. An aim of the proposed reforms is to achieve adequate data protection with a system that is easier to understand and comply with, and more consumer and business-friendly than before [17].
TGA updates its medicine adverse events database
The TGA has updated its Database of Adverse Event Notifications (DAEN) – medicines. The new version of the database allows users to interact with search results through dynamic tables, filters, and graphs [18, 19]
TGA approves psychedelics as medicines
From 1 July this year, medicines containing the psychedelic substances psilocybin and MDMA (3,4-methylenedioxy-methamphetamine) can be prescribed by specifically authorised psychiatrists for the treatment of certain mental health conditions. The TGA will permit the prescribing of MDMA for the treatment of post-traumatic stress disorder and psilocybin for treatment-resistant depression. These are the only conditions where there is currently sufficient evidence for potential benefits in certain patients. To prescribe, psychiatrists will need to be approved under the Authorised Prescriber Scheme by the TGA following approval by a human research ethics committee. The Authorised Prescriber Scheme allows prescribing permissions to be granted under strict controls that ensure the safety of patients [20]. Although not directly related to cell or gene therapy, this is an important event as it acknowledges the current lack of options for patients with specific treatment-resistant mental illnesses and Australia is the first country in the world to officially recognise MDMA and psilocybin as medicines [21].
New Zealand Therapeutic Products Bill
New Zealand consulted on a proposal to replace the current Medicines Act 1981 with the new Therapeutic Products Bill [22-24]. The ISCT ANZ LRA made a submission to the consultation.
Revised Current Medsafe Guidelines on the Regulation of Therapeutic Products in New Zealand
At the end of January 2023 Medsafe published a revised version of the Current Guidelines on the Regulation of Therapeutic Products in New Zealand, which covers regulatory requirements for medicines and related products, medical devices and labelling of medicines and related products (including other requirements are from earlier updates) [25].
Revised Current Medsafe Guidelines on the Regulation of Therapeutic Products in New Zealand
At the end of January 2023 Medsafe published a revised version of the Current Guidelines on the Regulation of Therapeutic Products in New Zealand, which covers regulatory requirements for medicines and related products, medical devices and labelling of medicines and related products (including other requirements are from earlier updates) [25].
2023 TGA GMP Forum
The 2023 Therapeutic Goods Administration GMP Forum was held at the Sydney Convention Centre on 21 March 2023. Approximately 600 delegates attended. The program covered a broad scope including inspections, common inspection deficiencies and trends, information for Australian sponsors & manufacturers, PIC/S Annex 1, adoption of future PIC/S revisions, GMP for Advanced Therapy Medicinal Products (ATMP), investigations and GMP Compliance Signals: Sponsors actions [26]
REFERENCES
[1] EMA, Hemgenix, https://www.ema.europa.eu/en/medicines/human/EPAR/hemgenix, approved 20 February 2023, accessed 22 March 2023
[2] Pharmaceutical Technology, CSL receives EC CMA approval for haemophilia B gene therapy, https://www.pharmaceutical-technology.com/news/csl-ec-haemophilia-b-gene-therapy/#:~:text=Biotechnology%20company%20CSL%20has%20received,(congenital%20Factor%20IX%20deficiency), published 21 February 2023, accessed 20 March 2023
[3] CISION PR Newswire, First Gene Therapy for Hemophilia B, CSL's HEMGENIX®, Approved by the European Commission, https://www.prnewswire.com/news-releases/first-gene-therapy-for-hemophilia-b-csls-hemgenix-approved-by-the-european-commission-301751222.html, published 20 February 2023, accessed 20 March 2023
[4] HEMGENIX, https://www.fda.gov/vaccines-blood-biologics/vaccines/hemgenix, content current as of 4 January 2023, accessed 22 March 2023
[5] CSL secures US approval for breakthrough one-time haemophilia gene therapy, https://biotechdispatch.com.au/news/csl-secures-us-approval-for-breakthrough-one-time-haemophilia-ge, published 24 November 24 2022, accessed 20 March 2023
[6] TGA, Notice for etranacogene dezaparvovec (CSL Behring Australia Pty Ltd), https://www.tga.gov.au/resources/designations-determinations/notice-etranacogene-dezaparvovec-csl-behring-australia-pty-ltd, date of review outcome 30 August 2022, accessed 22 March 2023
[7] CISION PR Newswire, Janssen Announces Unblinding of Phase 3 CARTITUDE-4 Study of CARVYKTI® (cilta-cel) as Primary Endpoint Met in Treatment of Patients with Relapsed and Refractory Multiple Myeloma, https://www.prnewswire.com/news-releases/janssen-announces-unblinding-of-phase-3-cartitude-4-study-of-carvykti-cilta-cel-as-primary-endpoint-met-in-treatment-of-patients-with-relapsed-and-refractory-multiple-myeloma-301732398.html, published Jan 27, 2023, accessed 20 March 2023
[8] N Stansfield, Janssen No Longer Seeking Approval for Carvykti in the UK, https://www.cgtlive.com/view/janssen-no-longer-seeking-approval-carvykti-uk, published 18 March 2023, accessed 21 March 2023
[9] MSAC, 1690 – Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T cell to treat refractory or relapsed multiple myeloma, http://www.msac.gov.au/internet/msac/publishing.nsf/Content/1690-public, updated 7 November 2022, accessed 20 March 2023
[10] Scoop Sci Tech, GMO Blood Cancer Therapy Gains EPA Approval, https://www.scoop.co.nz/stories/SC2208/S00036/gmo-blood-cancer-therapy-gains-epa-approval.htm, published 22 August 2022, accessed 20 March 2023
[11] The Royal Society, Third International Summit on Human Genome Editing, London https://royalsociety.org/science-events-and-lectures/2023/03/2023-human-genome-editing-summit/, 6-8 March 2023, accessed 22 March 2023
[12A] P Foong, Medical advances and ethical dilemmas in human genome editing, Progress Educational Trust (PET), BioNews, Issue 1183, https://www.progress.org.uk/medical-advances-and-ethical-dilemmas-in-human-genome-editing/, published 20 March 2023, accessed 22 March 2023
[12B] P Foong, Third global summit on human genome editing: Moving on after the He experiment, https://bioedge.org/featured/third-global-summit-on-human-genome-editing-moving-on-after-the-he-experiment/?fbclid=IwAR3hsf-tQjfdqhAuvQw6tJLa5ntFH01j_aln8YQ4YpZczcaVxhF44Dxp6jY, published 21 March 2023, accessed 24 March 2023
[13] National Clinical Trials Governance Framework, https://www.achs.org.au/our-services/accreditation-and-standards/accreditation-programs/national-clinical-trials-governance-framework/national-clinical-trials-governance-framework, published 2023, accessed 20 March 2023
[14] Fact Sheet National Clinical Trials Governance Framework – Overview, https://www.safetyandquality.gov.au/publications-and-resources/resource-library/fact-sheet-national-clinical-trials-governance-framework-overview, published 2022, accessed 20 March 2023
[15] Australian Government Attorney General’s Department, Privacy Act Review Report 2022 https://www.ag.gov.au/sites/default/files/2023-02/privacy-act-review-report_0.pdf, https://www.ag.gov.au/rights-and-protections/publications/privacy-act-review-report, published 16 February 2023, accessed 20 March 2023
[16] T Goatley, A Alford, Privacy Act Review Report: what to expect in the future of Australian Privacy Laws, Bell Gully, https://www.bellgully.com/insights/privacy-act-review-report-what-to-expect-in-the-future-of-australian-privacy-laws/, published 22 February 2023, accessed 20 March 2023
[17] T Goatley, O Zambuto, New UK GDPR proposals released, Bell Gully, https://www.bellgully.com/insights/new-uk-gdpr-proposals-released/, published 9 March 2023, accessed 20 March 2023
[18] TGA, DAEN – medicines update, https://www.tga.gov.au/news/news/daen-medicines-update, published 16 February 2023, accessed 19 March 2023
[19] TGA Database of Adverse Event Notifications (DAEN) – medicines, https://daen.tga.gov.au/medicines-search/, accessed 19 March 2023
[20] TGA, Change to classification of psilocybin and MDMA to enable prescribing by authorised psychiatrists, https://www.tga.gov.au/news/media-releases/change-classification-psilocybin-and-mdma-enable-prescribing-authorised-psychiatrists, published 3 February 2023, accessed 20 March 2023
[21] L Thorne, TGA approves psilocybin and MDMA for use in treating depression and PTSD, ABC News, https://www.abc.net.au/news/2023-02-03/tga-approves-psilocybin-mdma-for-treating-depression-ptsd/101929578, published 13 February 2023, accessed 20 March 2023
[22] Read the Bill, https://www.legislation.govt.nz/bill/government/2022/0204/latest/DLM6914502.html, accessed 20 January 2023
[23] Therapeutic Products Bill, https://www.parliament.nz/en/pb/sc/make-a-submission/document/53SCHE_SCF_BILL_130084/therapeutic-products-bill, published 15 December 2022, accessed 20 January 2023
[24] New Zealand Therapeutic Products Bill – About the Bill, https://www.parliament.nz/en/pb/bills-and-laws/bills-proposed-laws/document/BILL_130084/tab/hansard, accessed 20 January 2023
[25] Medsafe, Current Guidelines on the Regulation of Therapeutic Products in New Zealand,
https://www.medsafe.govt.nz/regulatory/current-guidelines.asp, revised 26 January 2023, accessed 23 March 2023
[26] 2023 TGA GMP forum program, https://www.tga.gov.au/gmp-forum-program, accessed 24 March 2023
STANDING GLOSSARY
Australian Register of Therapeutic Goods (ARTG): Therapeutic goods entered in the ARTG can be lawfully supplied in Australia (https://www.tga.gov.au/australian-register-therapeutic-goods)
Good Clinical Practice (GCP): An international ethical and scientific quality standard for designing, conducting, recording, and reporting clinical trials.
Good Manufacturing Practices (GMP): A set of principles and procedures that when followed helps ensure that therapeutic goods are of high quality.
Serious Scarcity Substitution Instrument (SSSI): Serious Scarcity Substitution Instruments (SSSIs) allow community pharmacists to substitute specific medicines without prior approval from the prescriber. SSSIs are made for a defined period and may be revoked sooner.
https://www.tga.gov.au/serious-scarcity-substitution-instruments-sssis
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