Cheryl Barton is director of PharmaVision, 

Cheryl Barton

The United Kingdom (UK) 2019 Voluntary Scheme for Branded Medicines Pricing and Access (VPAS) will end on 31 Dec. 2023. The UK’s 2019 VPAS succeeded several Pharmaceutical Price Regulation Schemes (PPRS) stemming back to 1957, and negotiations for the new VPAS between the UK government, National Health Service (NHS) England, and the Association of the British Pharmaceutical Industry (ABPI) began in May 2023 (1). The VPAS is one of two schemes, alongside the statutory scheme, that control the prices of branded medicines to the NHS (2).

The new VPAS will take effect from 1 Jan. 2024, and although profit control remains at the centre of the negotiations, the spotlight will be focused on keeping branded drugs affordable. The 2019 VPAs established a rise of 2% per annum from 2018–2023 for branded medicines, but historically, the spending on branded medicine has always exceeded the allowable growth rate (3). The ABPI notes that since 2021, the VPAS rebate resulted in member companies paying around 5% of their revenue back to the NHS and this increased to 15% in 2022 and 26.5% in 2023. It points out that the 2019 VPAS is no longer fit for purpose and needs to be overhauled (4).

On 20 Nov. 2023, a new deal was agreed between the UK government, NHS England, and the pharma industry which should save the NHS £14 billion over five years in medicines costs (5). The 2024 VPAS has reset the annual allowed growth in sales of branded medicines from 2% in 2024, rising to 4% by 2027. All older medicines that have not previously had price reductions will pay a top-up rate of up to 25% plus a base rate of 10% and the top-up will taper down for older medicines that have already been subject to price reductions (5).

Two Big Pharma companies, Eli Lilly and AbbVie, have already pulled out of the current VPAS voluntary pricing scheme (5), and Leslie Galloway, chair of the Ethical Medicines Industry Group (EMIG), warned “a survey showed that 50% of its members were reducing supplies of medicines in 2023 and a further 40% were discussing a reduction” (6). Thus, the 2024 VPAS needed to carefully balance affordability and allowable growth in order for the UK government to meet its goals of promoting better patient outcomes and a healthier population, supporting UK economic growth, and contributing to a financially sustainable NHS (

 UK Government’s and National Health Service England’s goals for 2024 Voluntary Pricing Scheme. 

According to Richard Torbett, chief executive at the ABPI, “This is a tough deal which underlines the essential role innovative medicines and vaccines will play in addressing the health challenges of the future. The industry supports this agreement, despite its restrictions, as it provides important support for patients and the NHS and commits to giving them access to the transformative treatments they need,” (5).

Under the new agreement, the pharmaceutical industry will also invest £400 million over five years through the Life Sciences Investment Programme to drive forward UK innovation, sustainability, and growth. The programme will be ring fenced to support work in:

pioneering clinical trials to bolster the NHS’s capacity to deliver commercial clinical research.

manufacturing helping to position the UK at the forefront of sustainable manufacturing by driving innovative advancements in environmental technologies and cultivating strategic partnerships.

innovative health technology assessments (HTAs) to support access to innovative medicines by developing novel approaches to HTA challenges (5).

The UK Generics and Biosimilar Medicines (BGMA) is concerned that its interests have not been fully considered and wanted more involvement in the VPAS negotiations (7). Disturbingly, some branded generic companies have already withdrawn products from the UK market as the operating environment was unviable (8). A new report shared with 

 indicates that post-Brexit red tape is leading to a significantly higher risk of drug shortages in the UK, in part due to the UK’s ability to acquire and stockpile medicines but also because of non-tariff issues and the difficult economic environment (9).

According to Mark Samuels, chief executive of the BGMA, “we are very disappointed that the price erosion mechanism (PEM) appears to damage competition because of how the reference price is calculated; it will reduce the plurality of medicine suppliers for the NHS, increasing the drug shortage risk … We are also concerned by the scheme using an originator product’s SPC status to confer whether a generic or biosimilar medicine that launches is defined as a new or older product,” (10).

The involvement of NHS England in negotiating medicine pricing and access has increased over recent years particularly, given its role in tendering as the Commercial Medicine Unit was brought in-house and it is the gatekeeper for Patient Access Schemes (PAPs) (11). The new agreement details how NHS England will work with companies to create a new PSP database to encourage local NHS services to partner with manufacturers and encourage the wider use of novel approaches to patient support post treatment (5).

This is one of the biggest economic and political debates that will have a significant impact on NHS patient access to cutting-edge treatments, the financial sustainability of the health service, and the competitiveness of the UK life science sector over the next five years. Although the BGMA is calling for further clarification regarding the reference pricing calculation for generics and biosimilars the new deal appears to be have been well-received by the pharma industry, and the new affordability mechanism for older medicines promises to support lower payment rates for more innovative branded medicines (5). Overall, the 2024 VPAS should allow the life science sector to grow faster than under the previous schemes and strengthen the UK’s global competitiveness.

Negotiations Begin for a New Medicine Pricing Scheme

Consultation Outcome Proposed Update to the 2023 Statutory Scheme to Control the Costs of Branded Health Service Medicines

, Consultation Outcome, Updated 2 March 2023.
3. ABPI. Voluntary Scheme on Branded Medicines. 

 (accessed Nov. 2023).
4. ABPI. At the Crossroads: How a New UK Medicines Deal can Deliver for Patients, the NHS, and the Economy. 

, Proposal Paper, March 2023.
5. ABPI. Landmark Medicines Deal to Boost Nation’s Health, Save NHS £14 Billion, and Support Research Investment. 

, New Release, 20 Nov. 2023.
6. Gershlick, P. Two Big Pharma Companies Leave NHS Pricing Scheme over Punitive VPAS Rebates. 

, Pharma Blog, 17 Jan. 2023.
7. Gershlick, P. 90% of Branded Pharma Could Reduce UK Medicines Supply in 2023. 

, Pharma Blog, 6 Dec. 2023.
8. Gershlick, P. BGMA Seeks Judicial Review to be Involved in New VPAS Negotiations Alongside ABPI. 

, Pharma Blog, 4 May 2023.
9. Gershlick, P. Crippling VPAS Rebate Scheme Killing Availability of Cheaper Generic Medicines. 

, Pharma Blog, 31 Oct. 2023.
10. BGMA. VPAG Heads of Agreement Reaction. 

, News Release, 21 Nov. 2023.
11. Forrest, A.; Thomas, R. NHS Patients Hit by ‘Severe Drug Shortages’ due to Brexit Red Tape. 

Cheryl Barton is director at PharmaVision, Pharmavision.co.uk.


Vol. 35, No. 12
December 2023
Pages: 7–8

When referring to this article, please cite it as Barton, C. Renewing the UK Voluntary Pricing Scheme. 

Articles

Renewing the UK Voluntary Pricing Scheme 

iofetamine (123i) molecule, molecular structure, iofetamine, ball and stick 3d model, structural chemical formula with colored atoms | Сергей Шиманович - stock.adobe.com

Ariceum Therapeutics, a private biotechnology company, based in Germany, is focused on developing novel drugs for systemic targeted radiation therapy (STRT) for hard-to-treat cancers. The name Ariceum is an anagram of ‘Marie Curie’ who discovered the elements radium and polonium, which have been hugely influential in the discovery of cancer treatments. The company was co-founded in 2021, and Ipsen transferred assets and all corresponding rights into the company on 22 Oct. 2021. Industry veteran Manfred Rüdiger, PhD, is the CEO of Ariceum, and Sandy McEwan, the company’s chief medical officer, is a world-renowned expert in oncology and nuclear medicine (1).

Over the past decade, significant advances have been made in radiation therapy, particularly in the development of systemic targeted radiopharmaceuticals to reduce potential side effects. Using an artificial intelligence (AI)-enabled platform, Ariceum has focused on designing novel targeting molecules that either bind to receptors on the tumour cell surface or the DNA within the tumour cells. This allows the radioactive payload to accumulate within the tumour and reduces exposure of healthy tissues to radioactivity (2).

Ariceum’s lead candidate in Phase II trials—beta-emitting lutetium-177 radiolabelled satoreotide tetraxetan (SS0110), a somatostatin type 2 (SST2) receptor antagonist—is being developed as a theranostic for the diagnosis and treatment of hard-to-treat cancers. SST2 receptors are overexpressed in many cancers, such as small cell lung cancer (SCLC), high-grade neuroendocrine tumours (NETs), and neuroblastoma, an aggressive, rare type of cancer that occurs mainly in young children (2). Satoreotide binds to the SST2 receptor on the tumour surface to deliver alpha and beta particles into the cancer cell within a radius of 1–10 mm of the receptor binding site.

The company recently published details of a Phase I/II trial, NCT02592707, assessing the safety and efficacy of satoreotide where it was shown to be safe and effective in patients with progressive, SSTR-positive NETs (3,4). A five-year long-term follow-up study is ongoing, and the study is due to be completed on 1 April 2025 (5). The company is also evaluating satoreotide in Phase II for SCLC, Phase I for Merkel cell carcinoma (MCC), and pre-clinical evaluation in solid tumours. In addition, Ariceum is evaluating SS0120, a gamma-ray-emitting Gallium-68 radiolabelled satoreotide trizoxetan as an imaging agent in patients with gastroenteropancreatic neuroendocrine tumours (6).

Ariceum’s second targeting molecule is a Poly (ADP-ribose) polymerase inhibitor (PARPi) which is expressed at a low level in healthy tissues compared to cancer cells (2). ATT001 is an iodine-125 radiolabelled PARP inhibitor (123I PARPi), which targets activated PARP bound to tumour DNA to release radiation in the cell nuclei through the emission of Auger electron (7). It is due to enter Phase I development for the treatment of glioblastoma following promising results in preclinical and first-human studies (8). In addition, ATD001 a fluorine-18 radiolabelled rPARPi is currently in Phase I clinical trials at Memorial Sloan Kettering Cancer Center. The first clinical study with ATD001 in head and neck cancers completed recruitment in May 2019 and trial data was published in 2020 (9).

In June 2023, Ariceum acquired UK-based biotech Theragnostics Ltd for US$44 million (€42 million)—US$2.5 million (€2.4 million) upfront plus cash and milestone payments totaling up to $41.5 million (€39.4 million)—to help expand its radiotherapeutic pipelines. The deal will enable Ariceum to gain access to NEPHROSCAN, a US Food and Drug Administration (FDA)-approved diagnostic developed in partnership with GE Healthcare, and gallium-68 (68Ga) kit technology intellectual property which is currently licensed to Novartis (10).

In June 2023, Ariceum signed a pharmaceutical multi-project agreement with Eurofins contract development and manufacturing organization (CDMO) to secure clinical trial services to support its Phase I/II clinical trial programme in Australia (11). In May 2023, the company signed a strategic research collaboration with UCB to discover new modalities for the treatment of immune-related diseases and cancers (10). UCB will leverage its proprietary messenger RNA-display platform, ExtremeDiversity, to support Ariceum in the discovery of three new peptide-radioisotope conjugates.

In June 2022, it completed a €25 million Series A financing round led by EQT Life Sciences (formerly LSP) HealthCap and Pureos Bioventures, and these funds will be used to advance its lead radiopharmaceutical product, satoreotide (1). In April 2023, Ariceum extended a Series A financing round to raise an additional €2.75 million funds to advance its clinical pipelines. New investors Andera Partners and Earlybird Venture Capital, join existing investor, Pureos Bioventures (12).

There is significant interest in radiotherapeutics, and several companies in Europe and the United States, including France-based Advanced Accelerator Applications (a Novartis Company) and Curium Pharma, and Germany-based ITM Isotope Technologies Munich SE, Germany, and US-based NuView, Telix Pharmaceuticals, RayzeBio, and Y-mAbs.

On 26 Sep. 2023, Genentech teamed up with Japan-based biopharmaceutical company PeptiDream to discover and develop novel peptide-radioisotope drug conjugates (13). According to the transaction terms, PeptiDream will receive an upfront payment of US$40 million (€38 million) from Genentech. PeptiDream will be eligible for potentially up to US$1 billion (€949 million) in payments based on certain development, regulatory, and commercial milestones.

On 3 Oct. 2023, Eli Lilly acquired POINT Biopharma for US$1.4 billion (€1.3 billion) to expand its oncology capabilities and gain access to next-generation radiotherapeutics (14). POINT’s lead programs in late-phase development include:

PNT20021 is a prostate-specific membrane antigen (PSMA) targeted radioligand therapy in development for patients with metastatic castration-resistant prostate cancer (mCRPC) after progression on hormonal treatment.

PNT20031 is an SSTR-targeted radioligand therapy in development for the treatment of patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs).

On 4 Oct. 2023, Novartis AG announced that it was considering selling part of the radiopharmaceuticals company, Advance Accelerator Applications (AAAs) as part of its business strategy to focus on high-risk, high-reward business units (15). AAAs pipeline includes Lutathera (lutetium-177 oxodotreotide) a first-line therapy against GEP-NETs, Netspot, and SomaKit which use 68Ga labelled somatostatin analogue to target neuroendocrine tumours, Locametz a 68Ga labelled prostate-specific antigen (PSA) and Gluscan, which tracks glucose metabolism with fluoride-18 (16).

Although radiation therapy has been used for years in the treatment of cancer technological radiotherapeutics are relatively new on the scene. Technological advances have improved the targeting of radiation therapy at the cellular level, and reduced side effects. Many of the larger pharma companies including AstraZeneca, Bristol Myers Squibb, Eli Lilly, Merck & Co, and Novartis have invested in this area and several agents have entered late-stage clinical development and/or entered the market. The next-generation radiotherapeutics offer significant potential to revolutionize the treatment of hard-to-treat cancers such as glioblastoma and neuroendocrine tumours, which up until now evaded treatment through traditional methods.

EQT Group. EQT Life Sciences Announces Launch and Series A Financing Round of portfolio company Ariceum Therapeutics. Press Release. 10 Jun. 2023.

Wild, D.; Grønbæk. H.; Navalkissoor, S. et al. A Phase I/II Study of the Safety and Efficacy of [177Lu]Lu-satoreotide Tetraxetan in Advanced Somatostatin Receptor-positive Neuroendocrine Tumors. Eur J Nucl Med Mol Imaging. 2023 Sep 18. doi: 10.1007/s00259-023-06383-1. Epub ahead of print. PMID: 37721581.

An International, Multicenter, Open-label Study to Evaluate Safety, Tolerability, Biodistribution, Dosimetry, and Preliminary Efficacy of 177Lu-OPS201 for the Therapy of Somatostatin Receptor-positive Neuroendocrine Tumors (NETs), NCT02592707. 

A Multicentre Surveillance Study to Evaluate the Long-term Safety in Participants Who Have Been Previously Treated With 177Lu-IPN01072 in an Ipsen-sponsored Clinical Study. NCT05017662. ClinicalTrials.gov (accessed 12 Oct. 2023).

Virgolini, I.; Bahri, S.; Kjaer, A.; et al. A Randomized, Factorial Phase II Study to Determine the Optimal Dosing Regimen for 68Ga-Satoreotide Trizoxetan as an Imaging Agent in Patients with Gastroenteropancreatic Neuroendocrine Tumors. 

, 63 (3), 376–383. doi: 10.2967/jnumed.121.261936. Epub 2021 Jul 2. PMID: 34215673; PMCID: PMC8978200.

Young, R.J.; Demétrio De Souza França P.; Pirovano, G.; et al. Preclinical and First-in-Human-Brain-cancer Applications of [18F]poly (ADP-ribose) Polymerase Inhibitor PET/MR. 

 2020 Sep 15;2(1):vdaa119. doi: 10.1093/noajnl/vdaa119. PMID: 33392502; PMCID: PMC7758909.

Schöder, H.; França, PDS.; Nakajima, R.; et al. Safety and Feasibility of PARP1/2 Imaging with 18F-PARPi in Patients with Head and Neck Cancer. 

, 26 (13), 3110–3116. doi: 10.1158/1078-0432.CCR-19-3484. Epub 2020 Apr 3. PMID: 32245901; PMCID: PMC7421489.

Ariceum Therapeutics. Ariceum Therapeutics Announces Extension of Series A Financing to EUR 47.75M to Advance its Next Generation Radiopharmaceutical Clinical Pipeline. Press Release. 1 Jun. 2023.

Ariceum Therapeutics. Ariceum Therapeutics, and Eurofins CDMO Sign a Pharmaceutical Multi-Project Agree

Ariceum Therapeutics. Andera Partners, and Earlybird Venture Capital Join Existing Investor, Pureos Bioventures. Press Release. 18 Apr. 2023

PeptiDream. PeptiDream Announces Collaboration and License Agreement with Genentech for the Discovery and Development of Novel Peptide-Radioisotope Drug Conjugates. Press Release. 19 Sept.2023.

Eli Lilly. Lilly to Acquire POINT Biopharma to Expand Oncology Capabilities into Next-Generation Radioligand Therapies. Press Release. 3 Oct. 2023.

Novartis. Novartis Executes Sandoz Spin-off, Completing the Strategic Transformation into a Leading, Focused Innovative Medicines Company. Press Release. 4 Oct. 2023.

Bloomberg. Novartis Weighs Selling Assets from Radiopharma Unit. Press Release. 3 Oct. 2023.

Cheryl Barton is director of PharmaVision, info@pharmavision.co.uk.


Vol. 35, No. 11
November 2023
Pages: 13-15

When referring to this article, please cite it as Barton, C. Frontrunners in Next-Generation Radiotherapeutics. 

New radiotherapeutic agents are making headway in hard-to-treat cancers.

Frontrunners in Next-Generation Radiotherapeutics

On 4 Sep. 2023, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) issued detailed guidance on the new International Recognition Procedure (IRP) for medicines manufacturers, including how to apply for a medicine licence (1). On 26 May 2023, MHRA announced new recognition routes would replace the current European Commission Decision Reliance Procedure (ECDRP) on 1 Jan. 2024 (2). The new process aims to bring cutting‑edge medicines faster to UK patients by leveraging the expertise and decision-making of trusted regulators in Australia, Canada, the European Union (EU), Japan, Switzerland, Singapore, and the United States (US) and enables MHRA to maintain its position as a sovereign regulator.

EU ‘reliance’ route to cease by the end of 2023

MHRA had previously introduced a temporary route to market for European-approved products in the UK, known as EU ‘reliance’ routes, to ensure that patients could continue to have timely access to new treatments. Currently, Regulation 58(4C) of the Human Medicines Regulations 2012 grants the power to MHRA to rely on the decision of the EC to approve a medicine in the UK for the MHRA to authorize that medicine in the UK without any further consideration, through a procedure known as the ECDRP. The EU ‘reliance’ route will cease on 31 Dec. 2023 and be replaced by the IRP following the completion of the MHRA public consultation, which is due to close on 30 Sep. 2023 (3).

The ECDRP provided market stability following the UK’s exit from the EU, but now the MHRA is in a position to implement a more considered approach to the assessments and accept applications from a wider range of partners. It is important to note that the ECDRP is one of four routes for products that use the EU reliance procedure. The MHRA continues to operate the remaining routes beyond the termination of the ECDRP. These include:

 This consortium is a collaboration of regulatory authorities including Australia, Canada, Singapore, and Switzerland. The UK joined the group in October 2020. The ACCESS consortium is based on a true work-sharing principle, to maximize international co-operation between partners, reduce duplication, and increase each agency’s capacity to ensure patients have timely access to high-quality, safe, and effective therapeutic products.

 This project provides a framework for concurrent reviews of oncology products among international partners. Project Orbis aims to deliver faster patient access to innovative cancer treatments that cater to an unmet medical need and demonstrate notable results (3).

The Mutual Recognition Decentralised Reliance Procedure (MRDCDRP). 

This procedure allows MHRA to take into account marketing authorizations (MAs) approved in EU member states (or Iceland, Liechtenstein, Norway) through decentralized and mutual recognition procedures to grant a MA in the UK (3).

The new IRP framework will be launched on 1 Jan. 2024 meaning all applications with a positive opinion from the Committee for Medicinal Products for Human Use (CHMP), received after 31 Dec. 2023, will be eligible (4). According to David Watson, executive director of Patient Access at the Association of the British Pharmaceutical Industry, “The MHRA’s pragmatic decision regarding GB marketing authorization applications is an important one for our industry. Pharmaceutical companies now have the clarity needed to inform their regulatory decisions for the year” (4).

The new IRP established two recognition timetables for initial MA applications:

Under “Recognition A”—a 60-day timetable will apply to approvals from other regulators granted within the previous two years provided the manufacturing process is the same as that already approved by the other regulator.

Under “Recognition B”—a 110-day timetable will apply to approvals granted within the previous 10 years and will be triggered if any one of a range of criteria is met (5).

MHRA has streamlined clinical trial approval

Earlier in the year, MHRA announced it would be combining regulatory and ethics reviews for trials to speed up approval times and make the UK more attractive for drug research (6). Results from pilot studies indicated that approval times for studies could be halved and the time cut from application to recruiting of the first patient by up to 40 days. MHRA also plans to introduce a 30-day deadline for reviewing clinical trial applications plus a maximum of 10 calendar days for a regulatory decision to be granted once the agency has received any final information (6).

MHRA’s decision to upgrade and streamline the regulatory review framework should help to speed up diagnosis and increase patient access to treatments whilst helping to propel the UK forward as a global leader in the life-science sector. In addition, the UK government’s proposal to set aside £10 million in funding to help accelerate the delivery of cutting-edge treatments, including cancer vaccines, should make it more attractive for scientists and researchers to work in the UK (6). On 11 Sep. 2023, it was announced that UK researchers and small to medium enterprises will be rejoining the Horizon Europe and Copernicus programme highlighting the important role that the UK hopes to play in the advancement of science now and in the future (7).

Guidance Published on the New International Regulatory Recognition Routes for Medicines Approvals

MHRA Announces New Recognition Routes To Facilitate Safe Access To New Medicines With Seven International Partners

Consultation on End to the European Commission Decision Reliance Procedure

, Open Consultation, 30 Aug. 2023.
4. ABPI. 

ABPI Response to MHRA European Commission Decision Reliance Procedure (ECDRP) Announcement

. Press Release, 24 Jan. 2023.
5. Fischer, N. 

MHRA Issues Guidance on New International Recognition Procedure (IRP) for Streamlining Medicine Approvals in the UK

MHRA to Streamline Clinical Trial Approvals in the Biggest Overhaul of Trial Regulation in 20 Years

, Press Release, 21 Mar. 2023.
7. UK Government. 

UK Joins Horizon Europe Under a New Bespoke Deal


Vol. 35, No. 10
October 2023
Pages: 8–9

When referring to this article, please cite it as Barton, C. MHRA Publishes New Guidance on International Regulatory Recognition Route. 

The new framework will position the UK as an attractive prospect for new medicine manufacturers.

MHRA Publishes New Guidance on International Regulatory Recognition Route 

TILT Biotherapeutics (TILT) is a Finland-based private biotechnology spin-out from the University of Finland focusing on the development of cancer immunotherapies utilizing oncolytic viruses encoded with a variety of cytokines to treat various cancers. The company was founded in 2013 by Akseli Hemminki, a cancer clinician, and aims to use an oncolytic virus to enhance T-cell therapy, including tumour-infiltrating lymphocytes (TILs), chimeric antigen receptor T cells (CAR-Ts), and checkpoint inhibiting antibody therapy of solid tumours (1).

The therapeutic benefit of various oncolytic viruses has been widely published in the literature, and researchers have improved the efficacy of first-generation products using genetic engineering (2). TILT coordinated a European Union (EU)-funded project, UNLEASHAD, which has developed an adenovirus-based oncolytic product, TILT-123 (igrelimogene litadenorepvec), that specifically targets and lyses cancer cells. It also releases TNF-α and interleukin-2 (IL-2) cytokines into the microenvironment, providing an alert and attracting immune cells to the tumour. This strategy ensures anti-tumour immunity and may be suitable for tumours that are refractory to other types of immunotherapies (3).

TILT-123 is currently in Phase I clinical trials as monotherapy and in combination with TIL therapy in Europe in metastatic melanoma. Preclinical results have been published, and the virus backbone has been demonstrated to be safe and well-tolerated in humans. Trials for other solid tumour indications are planned in combination with TILT-123 and a checkpoint modulator or a CAR-T product (2), and the company has other patent-protected products in the pipeline, including oncolytic viruses coding for bispecific antibodies TILT-321 and TILT-322 (3).

In May 2023, the company announced that the first patient had been dosed in a Phase I solid tumour trial, which will assess TILT-123 in combination with avelumab in squamous cell carcinoma of the head and neck (SCCHN) and melanoma in patients with advanced solid tumours refractory to, or progressing after, anti-programmed cell death ligand 1 (anti-PD-L1) (4). The study is part of TILT’s agreement with Merck KGaA, Darmstadt, Germany, and Pfizer, and the European trial is underway at the Docrates Cancer Center (Helsinki, Finland). The company expects to open its US site in the third quarter of 2023 (5). In November 2022, TILT opened an office in Boston to support its US clinical trial programme.

According to CEO Aseli Hemminki, “The oncolytic virus is designed with T cells in mind, and this design is based on patient observations, not just laboratory data. TILT-123 is armed with the most potent cytokines in the context of adaptive anti-tumour responses; it is genetically modified for improved access to cancer cells and for improved safety. Moreover, adenovirus is the most immunogenic virus type and is possible to upscale in manufacturing for industrial production. Importantly, TILT’s virus backbone has already been demonstrated safe in humans and can access distant tumours by vascular route. Therefore, in addition to intratumoural administration, the product can be administered by systemic route” (1).

TILT has partnered with Germany-based Merck KGaA, Switzerland-based MSD International GmbH, and US-based Pfizer (Merck-Pfizer Alliance). TILT is collaborating with the Cancer Gene Therapy Group at the University of Helsinki and with the University of Pennsylvania, where they are exploring the use of TILT‑123 in combination with CAR-Ts in solid tumours (6).

Since its conception, TILT has attracted more than US$42 million (€39 million) in private investment. On 7 Feb. 2023, it raised €22 million (US$23.8 million) from a financing round led by Finland’s Lifeline Ventures and €5.9 million (US$6 million) equity from the European Innovation Council (EIC) Fund as well as a €2.1 million (US$2.3 million) grant from EIC’s Accelerator programme. In addition, the company has received investments from Stephen Industries Inc Oy and ACME Investments SPF Sàrl. These funds will be used to advance the development of TILT-123 to Phase II clinical trials (7). This follows on from the first funding round of €10 million (US$10.9 million) in June 2022.

There is significant interest in TIL‑based therapeutics, and several companies both in Europe and the United States are exploring this route. In the US, TIL-based therapies are under development from: CTRL Therapeutics (8), Iovance Biotherapeutics (9), Obsidian Therapeutics (10), and Turnstone Biologics (11). Recently, Concerta Bioscience acquired Jounce Therapeutic to gain access to its first-in-class immunotherapy, which is designed to selectively deplete immunosuppressive tumour-infiltrating T regulatory cells in the tumour microenvironment (12).

Over the past few years, R&D efforts in the field of oncolytic viruses have received support from private investors and pharmaceutical companies. TILT’s leading programme, TILT-123, is progressing steadily through Phase I clinical development, and the company has raised sufficient funds to progress into Phase II trials. However, competition within this field is increasing as Concerta Biosciences, CTRL Therapeutics, and Obsidian Therapeutics have pre‑clinical candidates, and Turnstone Biologics has two Phase I trials underway with TILs. Meanwhile, Iovance Biotherapeutics has several Phase II trials nearing completion that are evaluating TILs as monotherapy and in combination with PD-1 or IL-2 analogues. Therefore, investors will be keen to see updates on TILT’s Phase II trial (NCT04217473), which is due for completion in February 2025 (13), and will be closely monitoring other competitor products as they progress through clinical development.

. 2017 13 (5), 970–971.
2. TILT Biotherapeutics. Next-generation Armed Oncolytic Immunotherapies. 

. May 2022.
3. EC. New Immunotherapy Tools to Fight Cancer. UNLEASHAD Project. Results in brief. H2020. CORDIS. 1 July 2018.
4. TILT Biotherapeutics. TILT Biotherapeutics Announces First Patient Dosed in Phase I Solid Tumours. Press Release, 15 May 2023.
5. TILT Biotherapeutics. TILT Biotherapeutics Announces Boston Office Opening as it Expands its Clinical Trials in the US. Press Release, 11 Sep. 2022.
6. TILT Biotherapeutics. Pipeline. 

 (accessed 17 Aug. 2023).
7. TILT Biotherapeutics. TILT Biotherapeutics Announces Final Close of €22 Million Financing. Press Release, 7 Feb. 2023.
8. cTRL Therapeutics. Accessible Cell Therapy (accessed 17 Aug. 2023).
9. Iovance Biotherapeutics, Investigating TIL Therapy & PBL Therapy for Cancer (accessed 17 Aug. 2023).
10. Obsidian Therapeutics. Our Lead Clinical Program (accessed 17 Aug. 2023).
11. Turnstone Biologics. Leading the Fight Against Solid Tumours (accessed 17 Aug. 2023).
12. Jounce Therapeutics. Jounce Therapeutics Enters Into an Agreement to Be Acquired by Concentra Biosciences for $1.85 in Cash per Share Plus Contingent Value Rights. Press Release, 27 Mar. 2023.
13. A Phase 1, Open-Label, Dose-Escalation Clinical Trial of Tumour Necrosis Factor Alpha and Interleukin 2 Coding Oncolytic Adenovirus TILT‑123 in Melanoma Patients Receiving Adoptive Cell Therapy With Tumour Infiltrating Lymphocytes. 

classic.clinicaltrials.gov/ct2/show/NCT04217473

Cheryl Barton is director of Pharmavision, info@pharmavision.co.uk.


Vol. 35, No. 9
September 2023
Pages: 14–15

When referring to this article, please cite it as Barton, C. Harnessing the Power of Oncolytic Viruses. 

Tumour-infiltrating lymphocyte (TIL) therapies offer a new route to target cancer.

Harnessing the Power of Oncolytic Viruses

On 5 May 2023, the World Health Organization (WHO) declared that COVID-19 was no longer a public health emergency following a decrease in COVID-19 deaths, hospitalizations, and intensive care unit admissions across the globe over the past several months (1). On 6 July 2023, the European Medicines Agency (EMA), the European Commission (EC), and the Heads of Medicine Agencies (HMA) announced they would be phasing out the extraordinary COVID-19 regulatory flexibilities introduced in August 2022 in response to the pandemic (2).

Extraordinary regulatory flexibilities introduced during COVID-19

The extraordinary regulation encompassed several different aspects to ensure the continuity of supplies of medicines during the public health emergency. These included greater flexibility for:

good manufacturing practice (GMP) and good distribution practice (GDP) issues

issues related to marketing authorization (MA) and MA procedures

manufacturing and importation of finished products and APIs (3).

EMA’s quick response to the crisis highlighted the need for rapid and coordinated feedback to developers and the importance of continued dialogue with them, to ensure that adaptions to the regulatory environment were workable for the industry (4).

From this point onwards, the regulatory flexibilities that were introduced jointly by the EC, EMA, and HMA during COVID-19 will no longer be granted (3). For products that have already received approved labelling flexibilities, such as COVID-19 vaccines with English-only labelling, the application will be extended until the end of 2023 to prevent any disruptions to supplies; after which time, manufacturers will revert to the original legislations on product labelling (3).

Conversely, on-site GMP and GDP inspections have been reinitiated following their postponement or implementation of remote visits performed during the pandemic (3). GMP and GDP certificates have been extended until the end of 2023, and the GMDP inspectors working group will provide further details over the coming months following a review of information gleaned from remote working of qualified persons during the pandemic (5).

Future regulation, preparedness, and response tools

The COVID-19 pandemic highlighted the importance of deploying a coordinated EU-wide strategy and revealed some vulnerabilities in the current system, including limitations in the regulations, preparedness, and response tools (6). In November 2020, the EC proposed a series of measures, including a revised regulation on serious cross‑border threats to health and proposals to extend the mandates of EMA and the European Centre for Diseases Prevention and Control (ECDC) in public health emergencies, to create a European Health Emergency Preparedness and Response Authority (HERA) (7). In February 2021, the EC also announced that it may consider targeted amendments to the pharmaceutical legislation including developing new regulatory tools to introduce an emergency authorization of vaccines at the EU level with shared liability among member states, during public health threats (6).

On 26 April 2023, EMA published two legislative proposals—a new regulation 2023/0131 and a new directive 2023/0132—to replace the current European Union (EU) regulatory framework for all medicines (8,9). As part of the overhaul, EMA plans to introduce some contingency planning procedures including the compilation of an EU-wide list of critical medicines and recommendations to companies to strengthen the supply chains should the need arise. Under the new proposal, all MA holders will need to put in place a shortage prevention plan for each medicine on the market, any critical shortages would need to be reported to EMA. In addition, the new regulation provides temporary measures such as emergency MA for crisis‑related medicines allowing the EU to take control of drug manufacturing in response to an emergency, this controversial point has raised concerns amongst some pharma industry leaders (10).

The new regulatory framework is currently being reviewed by the European Parliament and the European Council and a decision on the proposed reform is unlikely to take place before the 2024 EU parliamentary elections. In the meantime, data are being gathered by EMA’s Executive Steering Group on Shortages and Safety of Medicinal Products regarding manufacturers’ experience of the COVID-19 regulatory flexibilities (11). EMA will then reflect on how lessons learned during the pandemic can inform best practices for confronting medicine shortages in the presence of new and emerging health challenges in the future (2).

Statement on the Fifteenth Meeting of the IHR (2005) Emergency Committee on the COVID-19 Pandemic

Phasing out of Extraordinary COVID-19 Regulatory Flexibilities

Questions and Answers on Regulatory Expectations for Medicinal Products for Human Use During the COVID-19 Pandemic

, 11 Aug. 2022.
4. Cavaleri, M.; Sweeney, F.; Gonzalez-Quevedo, R.; Carr, M. Shaping EU Medicines Regulation in the Post-COVID-19 Era. 

, 9, 100192.
5. Taylor, N.P. Euro Roundup: EMA Starts Phasing Out Regulatory Flexibilities Provided During the COVID-19 Pandemic. 

, RAPS, 13 July 2023.
6. Beaussier, A.; Cabane, L. Strengthening the EU’s Response Capacity to Health Emergencies: Insights from EU Crisis Management Mechanisms. 

HERA Incubator: Anticipating Together the Threat of COVID-19 Variants

Reform of the EU Pharmaceutical Legislation

Proposal For a Regulation of the European Parliament and of the Council Laying Down Union Procedures for the Authorization and Supervision of Medicinal Products for Human Use And Establishing Rules Governing The European Medicines Agency, Amending Regulat

. Regulation, 26 April 2023.
10. Barton, C. 

EMA Overhauls the Medicine Legislative and Regulatory Framework

Executive Steering Group on Shortages and Safety of Medicinal Products

When referring to this article, please cite it as Barton, C. Phasing Out COVID-19 Regulatory Flexibilities. 

What impact will EMA’s decision to phase out COVID-19 regulatory flexibilities have on the pharma industry?

Phasing Out COVID-19 Regulatory Flexibilities

On 26 April 2023, the European Medicines Agency (EMA) published two legislative proposals—a new Regulation 2023/0131 and a new Directive 2023/0132 to replace the current European Union (EU) regulatory framework for all medicines (1,2). This legislative proposal will amend the current regulations on advanced therapy medicinal products (ATMPs) (3) and clinical trials (4), while also repealing the regulation that sets out the procedures for authorization and supervision of medicinal products (5), and the regulations for rare disease and medicines for children (6). The new regulation aims to make medicine more widely available, accessible, affordable, and sustainable, and to drive innovation and enable the European pharma industry to compete in the wider arena.

The proposal aims to reduce the timeframe of the approval procedure from the current average of 400 days, by cutting regulatory review times from 210 days to 180 days for most medicines and 150 days for medicines that are of major interest to public health. It also reduces the time taken for receiving a decision on marketing authorizations (MA) following recommendations from EMA, from 67 days to 46 days.

EMA will also simplify its structure from five to two main scientific assessment committees for human medicines: the Committee for Human Medicinal Products and the Pharmacovigilance Risk Assessment Committee (PRAC). The current ATMP, orphan, and paediatric committees will be discontinued.

In addition, EMA plans to adopt a “rolling review” system similar to the one that was implemented during the COVID-19 pandemic, which will allow the regulators to examine clinical trial data as they become available, rather than waiting for a single submission once all clinical trials are complete (7).

Potential changes to regulation protection periods

The revised legislation will overhaul the legislative framework and could result in a maximum patent protection of up to 12 years compared to 11 years for non-orphan drugs; however, this will result in market exclusivity being reduced from 10 years (eight years of data exclusivity plus two years of market exclusivity) to eight years (six years of data exclusivity plus two years of market exclusivity). However, new medicines may extend the period of protection by:

addressing an unmet medical need (an additional six months)

conducting comparative clinical trials (an additional six months)

developing a new therapeutic indication (an additional one year)

launching the new medicine in all EU member states (an additional two years).

Similarly, market exclusivity of orphan drugs could result in a maximum patent protection of up to 13 years compared to the current 10-year span for orphan drugs. The standard market exclusivity period will be reduced from 10 years to nine years; however, orphan medicines may benefit from additional periods of protection, increasing the total period up to a maximum of 13 years, with additional increments being available by:

launching the new medicine in all EU member states (an additional year)

addressing a high unmet medical need (an additional one year)

developing a new therapeutic indication (up to an additional two years) (7).

Thus, the new regulation is likely to reduce the period of regulatory protection granted for innovator companies given that it is extremely challenging to gain approval in addition to pricing and reimbursement (P&R) in all member states—P&R is governed by national law and not in the control of the MA holder.

The European Federation of Pharmaceutical Industries and Associations (EFPIA) is concerned that changes in market protection will undermine pharma’s future investment in R&D and the development of innovative medicines (8). Responding to the proposed changes, Nathalie Moll, director general of EFPIA commented, “The approach set out in the pharmaceutical legislation, penalizing innovation if a medicine is not available in all member states within two years, is fundamentally flawed and represents an impossible target for companies. The vast majority of delays in access to new medicines are known to occur after a company has filed for pricing and reimbursement and is awaiting a decision so that the new treatment can be made available to patients” (8).

In terms of contingency planning, EMA will compile an EU-wide list of critical medicines and will provide recommendations to companies to strengthen the supply chains should the need arise. Under the new proposal, all MA holders will need to put in place a shortage prevention plan for each medicine on the market, any critical shortages would need to be reported to EMA.

The new regulation also provides temporary measures such as emergency MA for crisis-related medicines allowing the EU to take control of drug manufacturing in response to an emergency. This point has raised concerns amongst the pharma industry as compulsory licensing could weaken pharma’s ability to protect its intellectual property (IP). In an interview with the Financial Times, Vas Narasimham, the CEO of Novartis, noted that “compulsory licensing will damage the ecosystem for emergency response” (9).

Incentives to tackle microbial resistance

EMA aims to incentivize the industry to develop novel antimicrobial resistance through the introduction of transferable data-exclusivity vouchers, which would grant an additional year of data exclusivity for any medicine and can be sold to other companies (10,11). The vouchers will be provided in limited numbers over a limited period; a maximum of 10 vouchers over 15 years. Strict rules will apply to their transfer and use.

Under the proposed changes, within 30 days of receiving a MA, pharmaceutical companies will be required to publish information regarding all direct financial support for the R&D of medicines received from public authorities or publicly funded bodies.

MA applicants are already required to include an environmental risk assessment (ERA) of the medicine; however, the EC will strengthen the use of the ERAs to reduce the potential adverse impacts of medicines on the environment and public health. Under the new proposals, medicine approvals may be refused if a company does not provide adequate evidence that environmental risks were evaluated, and risk mitigation measures were taken.

Currently, pharmacies are only allowed to prepare and dispense products in response to individual prescriptions. The legal proposal allows hospital pharmacies greater flexibility to prepare a product for dispensing medicines and clarifies rules on hospital exemptions (12).

The Council of the EU is in discussion with its preparatory bodies and will provide the legislative proposal to the European Parliament and the European Council for their consideration. It remains to be seen how the pharma industry will respond to the new proposal given the intense pressure companies are under to lower drug prices whilst recouping a return on investment. In the meantime, EFPIA is committed to working with members of the European Parliament, the Council of the EU, and other stakeholders “to ensure the revised pharmaceutical legislation and patent package meets the needs of patients, our healthcare systems, member states, and Europe’s life science sector” (8).

No timelines on the adoption of this new regulatory framework are forthcoming, but it is unlikely that the proposed reform will take place before the 2024 EU parliamentary elections.

Proposal For a Regulation of the European Parliament and of the Council Laying Down Union Procedures for the Authorization and Supervision of Medicinal Products for Human Use And Establishing Rules Governing The European Medicines Agency, Amending Regulation (EC) No 1394/2007 and Regulation (EU) No 536/2014 and Repealing Regulation (EC) No 726/2004, Regulation (EC) No 141/2000 and Regulation (EC) No 1901/2006

Regulation (EC) No 1394/2007 of the European Parliament and of the Council of 13 November 2007 on Advanced Therapy Medicinal Products and Amending Directive 2001/83/EC and Regulation (EC) No 726/2004 

Consolidated Text: Regulation (EU) No 536/2014 of the European Parliament and of the Council of 16 April 2014 on Clinical Trials on Medicinal Products for Human Use, and Repealing Directive 2001/20/EC

Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 Laying Down Community Procedures for the Authorization and Supervision of Medicinal Products for Human and Veterinary Use and Establishing a European Medicines Agency 

Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on Medicinal Products for Paediatric use and Amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004

 (12 Dec. 2006).
7. Worden, T; Nauth, L. The European Commission Proposes First Major Overhaul of the EU Medicines Regulatory Framework in 20 Years. 

, Alert, 27 April 2023.
8. EFPIA, EU Pharma-Legislation Risks Sabotaging Europe’s Life Science Industry Putting European Patients Further Away from Cutting-Edge Healthcare. 

, 26 April 2023.
9. Mancini, D.P.; Kuchler H., Novartis Chief Criticizes EU Move to Control Pharma Licensing in Emergencies. 

Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions Reform of the Pharmaceutical Legislation and Measures Addressing Antimicrobial Resistance

Proposal for a Council Recommendation on Stepping Up EU Actions to Combat Antimicrobial Resistance in a One Health Approach

 (12 May 2023).
12. Castle, G.; Bogaert, P.; Doyle-Rossi, M. EU Pharma Legislation Review Series: The EU’s Proposals to Amend its Pharmaceutical Laws Released Today. 

Cheryl Barton is director of PharmaVision, info@pharmavision.co.uk

When referring to this article, please cite it as Barton, C. EMA Overhauls the Medicine Legislative and Regulatory Framework. 

What implications will EMA’s recent regulatory reform have on pharma?