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ANZ LRA Watchdog Update – April 2025

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Co-Authors:

Gabrielle O’Sullivan, PhD, MPH(Hons)
Royal Prince Alfred Hospital
Australia

Paula Stoddart
Miltenyi Biotec
Australia

AUSTRALIAN AND NEW ZEALAND REGULATORY UPDATES

AOTEAROA – NEW ZEALAND

New Zealand Ministry of Health

Following decisions by the New Zealand Government in September 2024, the Ministry of Health is developing a new Medical Products Bill to replace the Medicines Act 1981 and modernize medicines and medical devices regulation in New Zealand. The Government agreed that the new Bill would regulate medicines and medical devices, and that natural health products would be regulated under a separate standalone bill. There will be consultation with consumers, industry and practitioners on the resulting future regulations. It is intended for the new Medical Products Bill to be passed in 2026 and then come into effect in 2028. Meanwhile, the Government has repealed an earlier short lived Act (the Therapeutic Products Act) that was once intended to replace the Medicines Act 1981 until a decision was made to repeal it in order to replace the Medicines Act 1981 with the new Medical Products Bill. [1- 3]

New Zealand Gene Technology Bill

The New Zealand government has introduced the Gene Technology Bill 2024 which is intended to replace the existing regulatory regime for gene technology and genetically modified organism (the Hazardous Substances and New Organisms Act 1996 (HSNO Act)) with modernized, flexible and risk-proportionate regulation, efficient decision-making processes, and international alignment to facilitate trade and technological advancements. The Bill was introduced for initial consideration on December 10, 2024 and passed its first reading in Parliament on 17 December 2024, and was referred to the Health Select Committee. There was public consultation on Bill which closed on 17 February 2025. The Bill provides for a dedicated gene technology regulator within the Environmental Protection Authority who will conduct assessments and provide for the management of risks of GMOs, and release information to the public, guidance to the regulated community, and advice on technical matters to Ministers (analogous to the OGTR in Australia). There will also be risk tiering [4-7]

Medsafe

Medsafe has communicated that it is encouraging the reporting to it of pyoderma gangrenosum cases that may be associated with an anti-CD20 monoclonal antibody. Pyoderma gangrenosum (PG), a rare inflammatory skin disease, has been reported internationally during treatment with anti-CD20 monoclonal antibodies (rituximab, ocrelizumab, obinutuzumab and ofatumumab). The Medicines Adverse Reaction Committee (MARC) reviewed the possible association between PG and anti-CD20 monoclonal antibodies at their 199th meeting in September 2024. They considered that the current evidence for a causal link is weak and recommended that Medsafe publish a monitoring communication to gather more information. [8]

AUSTRALIA

Medical Services Advisory Committee (MSAC)

On 29 November 2024, MSAC supported an updated funding proposal to the Department of Health and Aged Care from Janssen-Cilag (the applicant) in relation to the public funding of ciltacabtagene autoleucel (cilta-cel, CARVYKTI®)) in patients with relapsed or refractory multiple myeloma (RRMM) as a Highly Specialised Therapy through the National Health Reform Agreement (NHRA), jointly funded by the Commonwealth and State and Territory governments. Ciltacabtagene autoleucel (cilta-cel) is an autologous chimeric antigen receptor T (CAR-T) cell therapy for treatment of patients with multiple myeloma (MM) who are refractory or have failed more than three lines of prior therapy. [9]

In the TGA approval, CARVYKTI is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, and are refractory to lenalidomide or who have received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody [10].

It is interesting to note that in the UK CARVYKTI is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide [11].

Therapeutic Goods Administration (TGA)

The TGA has updated a number of its mechanisms for meeting TGA regulatory requirements by providing:

· Forms for applying to become an Authorized Prescriber [12] and for applying for use of the Special Access Scheme [13].

· A recall reforms update and new procedure [14]

· An automatic extension until 31 December 2025 of GMP Clearances issued via the Mutual Recognition Agreements (MRA) pathway that were due to expire on 31 December 2024 [15]

It has also addressed misinformation about excessive DNA in mRNA vaccines [16]. The OGTR has also addressed misinformation about mRNA COVID-19 vaccines by stating that mRNA COVID-19 vaccines are not gene therapies [17].

Office of the Gene Technology Regulator (OGTR)

The OGTR has issued licences for a ‘Clinical trial of GM vaccinia virus for the treatment of solid tumours’ (DIR 208, issued 11 March 2025) [18] and a ‘Clinical trial for the treatment of mycobacterial infections using bacteriophages’ (DIR 206, issued 10 February 2025) [19].

The bacteriophage trial is novel and the licence for it (DIR 206) allows Western Sydney Local Health District to conduct a clinical trial of a genetically modified (GM) bacteriophage treatment for the treatment of mycobacterial infections in Australia. It is hoped that this GM bacteriophage treatment offers an option to patients with multi-drug resistant mycobacterial infections, where standard measures either do not exist or are no longer effective. Normally when bacteriophages infect a bacterial cell, they typically either live inside the bacterial cell, or reproduce and kill the cell. The GM bacteriophages have been modified to remove the ability to live in bacteria, so they can only reproduce in the bacteria and destroy the infection. Participants in the trial are eligible under the Special Access Scheme categories A and/or B. At least 3 participants will take part in the trial over 5 years. [19]

INTERNATIONAL REGULATORY UPDATES RELEVANT TO AUSTRALIA & NEW ZEALAND

British Pharmacopoeia (BP)

The British Pharmacopoeia (BP) has consulted on a draft update to the guidance for Vector Copy Number, which includes a revision to the guidance itself as well as new Polymerase Chain Reaction validation plans. This update will be helpful to a range of stakeholders including those in GMP regulated environments, research and development, academia, and clinical trials. [20]

United States (FDA)

In January 2025, the FDA issued a draft ‘Guidance Document on Considerations for the Use of Artificial Intelligence To Support Regulatory Decision-Making for Drug and Biological Products’ [21]. The guidance discusses the use of AI models in the drug product life cycle to produce information or data to support regulatory decision-making regarding safety, effectiveness, or quality for drugs. It does not address AI in drug discovery or operational efficiencies that do not impact patient safety, drug quality, or the reliability of results from a nonclinical or clinical study. It describes a risk-based credibility assessment framework to help with planning, gathering, organizing, and documenting information to establish the credibility of AI model outputs in the context of the particular AI model risk and Context of Use (COU) in question when the model is used to produce information or data intended to support regulatory decision-making. It also addresses lifecycle maintenance of the credibility of AI model outputs. [21]

On 5 March 2025, the FDA approved ENCELTO (revakinagene taroretcel-lwey), which is a new gene therapy for the treatment of adults with idiopathic macular telangiectasia type 2 (MacTel), a rare eye disease that causes vision loss. ENCELTO consists of implantable encapsulated allogeneic retinal pigment epithelial cells expressing recombinant human ciliary neurotrophic factor (rhCNTF) [22, 23].

On 19 December 2024, the FDA approved SYMVESS, which is a sterile, acellular tissue engineered vessel composed of human extracellular matrix (ECM) proteins typically found in human blood vessels. SYMVESS is 6 mm in internal diameter and 42 cm in length (approximately 40 cm of usable length) and exhibits mechanical and biological activity. Product testing has shown that SYMVESS can withstand the forces associated with the arterial blood flow and suturing during implantation. [24]

Earlier in 2024, on March 18, the FDA approved LENMELDY (atidarsagene autotemcel, OTL-200) for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). MLD is a rare, autosomal recessive lysosomal storage disease, primarily due to a deficiency in the arylsulfatase A (ARSA) enzyme. LENMELDY is an autologous hematopoietic stem cell-based gene therapy, which contains a CD34+ cell enriched population originating from hematopoietic stem and progenitor cells (HSPCs), transduced ex vivo with a replication-incompetent self-inactivating lentiviral vector (LVV) expressing the human arylsulfatase (ARSA) gene (ARSA LVV) [25]. After LENMELDY infusion, transduced CD34+ HSCs engraft in bone marrow, repopulate the hematopoietic compartment and their progeny produce ARSA enzyme. Functional ARSA enzyme can breakdown or prevent the harmful accumulation of sulfatides.

Europe (EMA) - The continued threat of unproven cell therapies

On 13 March 2025, the EMA and the Heads of Medicines Agencies (HMA) issued a warning to the public about the dangers of unregulated advanced therapy medicinal products (ATMPs) offered to patients in the European Union.

However, a number of individuals, companies and clinics have been marketing unregulated ATMPs directly to patients, often when there is little or no evidence that the products work or are safe. Some of the unregulated products in the EU are sold as dendritic cell therapies, which use dendritic cells to attack cancer cells. [26]

Japanese Society for Regenerative Medicine (JSRM)

In response to growing international concerns about the proliferation of unverified regenerative medicine practices provided under Japan’s Act on the Safety of Regenerative Medicine (ASRM), JSRM announced the YOKOHAMA Declaration 2025 on 19 March 2025 which explicitly distinguishes the categories of Explorative Therapy and Uninvestigated Therapy to clearly differentiate scientifically valid treatments from those lacking sufficient scientific scrutiny. [27, 28]

Expanded access

The ISCT Expanded Access Working Group has published a position paper on key considerations to support equitable and ethical expanded access to investigational cell- and gene-based interventions. It explores how investigational therapies are accessed outside of clinical trials for patients with serious or life-threatening conditions when no approved alternatives exist and the challenges faced by healthcare professionals in navigating the balance between access and oversight. Key considerations include transparent communication with patients, robust data reporting, and a discussion of cost recovery models and their implications for long-term commercialization strategies, equity and inclusivity, the need to design pathways that are accessible to diverse patient populations while upholding high scientific and ethical standards. [29]

PRICING

Mesoblast (NASDAQ:MESO) has announced the pricing and upcoming availability of its FDA-approved product Ryoncil® for treating steroid-refractory acute graft versus host disease (SR-aGvHD) in pediatric patients. The wholesale acquisition cost is set at US$194,000 per infusion.

The company reported that Ryoncil® demonstrated a 70% overall response rate in Phase 3 trials, with 49% survival through 4 years. The treatment's total benefits range from US$3.2-4.1 million per patient. Mesoblast has established MyMesoblast™ hub for patient services and partnered with Cencora for distribution.

Financial highlights include a cash balance of US$38 million as of December 31, 2024, with pro-forma cash of approximately US$200 million after completing a US$161 million global private placement. The company reported a net loss of US$47.9 million for H1 FY2025, with net operating cash spend reduced by 22% to US$20.7 million compared to H1 FY2024. [30]

There has been much public commentary on the pricing of Ryoncil® including that it would be $1.55M per patient if all the infusions are completed [31] and that Temcell®, an equivalent manufacture MSC product is about $170,000 for the whole treatment [32, 33].

AUSTRALIAN FEDERAL ELECTION

The Australian Federal election will be held on 3 May 2025 [34]

References