While the broad promise of Novosorb neodermis cell delivery is its potential as a platform technology capable of delivering multiple cell types for therapeutic use in multiple indications, the immediate opportunity here for PolyNovo lies in the use of Novosorb to deliver human pancreatic islet cells to treat type 1 diabetes.
Allogeneic islet-cell-transplantation (ICT) is already recognized as a safe and efficacious therapy for selected patients with type 1 diabetes.
As explained in the presentation given by Prof. Coates this week, the current practice for ICT is to transplant allogeneic human islets into the liver via the portal vein. But this practice comes with multiple drawbacks
… up to 75% of the transplanted islet mass is lost within the first 48 hours post-transplant, due to the Instant Blood Mediated Inflammatory Reaction. Furthermore, the hepatic transplant site is unable to be easily biopsied, transplanted islets are unable to be monitored or retrieved, limiting the ability to detect and treat islet graft rejection. (1)
The Coates/Greenwood patent states that these drawbacks are addressed by the neodermis cell delivery invention. Other advantages of the invention are also noted - the procedure can be performed under minimal sedation as an outpatient procedure; subsequent significant cost savings associated with treatment; a potential reduction in the number of islet infusions required for insulin independence and a way of implanting cells that allows for local application of drugs, such as immunosuppressants.
Over the past two decades, there have been thousands of ICT procedures carried out in over 2,000 patients, predominantly in Europe, Canada, and Australia. (2,3)
Noticeably absent from that list of locations is the United States. That’s because the US FDA regulates pancreatic islet cell transplantation as a biologic drug for allogeneic use (thus using a BLA regulatory pathway) while Europe, Canada, Australia and Japan regulate islets as a tissue or organ. (4)
The FDA approved the first allogenic pancreas islet cell product, CellTrans’ cellular therapy, Lantidra, in 2023. Approval was based on clinical data from just 30 patients across two open-label, single-arm trials using the endpoint of insulin independence, which the FDA deemed to be clinically meaningful. 90% of the patients had at least one serious adverse reaction with the most common adverse reactions related to the need for immunosuppressive medications to maintain islet cell viability. Despite the surprise approval for CellTrans, to date, no transplants using Lantrida have been performed. (5)
The medical use of living cells, tissues and genetic materials has become increasingly complex (from a scientific, legal and regulatory standpoint) as scientists endeavour to address critical issues such as organ scarcity, graft rejection, and the long-term viability of transplant outcomes.
In response, the EU has created a new class of medicines - Advanced Therapy Medicinal Products (ATMPs). ATMPs are categorized into four separate groups - gene therapies, somatic cell therapies, tissue-engineered therapies and combined advanced therapies. (6)
The EMA has recently issued guidelines on quality, non-clinical and clinical requirements for ATMPs in clinical trials. The guidelines come into effect on July 1 this year. This is what is said about ATMP-device combinations.
ATMP-device combinations
This section addressed the following situations:
ATMPs with co-packaged medical devices;
ATMPs with referenced medical devices;
ATMPs with an integral medical device.
If a medical device is used, its regulatory status should be explicitly stated (e.g. whether it is CE marked for its intended purpose or not). If it is certified for the intended purpose the CE certification should be provided.
In the first two situations, the medical device is non-integral and an independent entity subject to the requirements of the medical device legislation. Acknowledging the different legislations for medicines, ATMPs and medical devices, in the context of the clinical trial, the potential impact of the device on the quality, safety and/or efficacy of the ATMP needs to be addressed and the safe and effective use of the medical device in combination with the ATMP shall be supported by data in the submission dossier. Non-integral medical devices combined with ATMPs can be either independently developed or co developed with the ATMP in which case they would not yet be certified. CE-marking for the intended use should be obtained in parallel with the marketing authorisation for the device to be legally on the market. For co-developed devices, a single study protocol may serve to demonstrate the efficacy and safety profile of the ATMP and the suitability of use of the device. The protocol will have to take into account the requirements of both the medical device and medicinal product legislation and will need to address the device-ATMP interactions and interdependencies. The clinical trial application and the clinical investigation will have to be submitted in parallel to the medicinal product and medical device competent authorities. In case the protocol is not integrated, a statement of compliance of the medical device with relevant legal requirements for safety and performance is required as part of the clinical trial submission dossier.
Where the ATMP has an integral medical device component the overall product is governed by the medicines legislation and a CE mark is not required. The scientific data supporting the device component will have to be proportionate to its role in the context of the overall product, i.e. as integral delivery device or part of the product to be administered. The data supportingthe safe and effective use need to be submitted with specific reference to relevant General Safety and Performance Requirements (GSPR) of the Medical Device Regulation. (7)
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