Advancing therapy – European innovation in a time of post-COVID-19 Leave a comment

Good afternoon, health colleagues, and welcome to the European Alliance for Personalised Medicine (EAPM) update – it has certainly been busy for EAPM of late, with Advanced Therapy Medicinal Products (ATMPs), writes EAPM Executive Director Dr. Denis Horgan.

Advanced Therapy Medicinal Products (ATMP)

EAPM has recently published an article on Advanced Therapy Medicinal Products (ATMPs) – this was created with a group of experts, and this represents the EAPM perspective on the issue. It is an issue that is very much being discussed at EU level – Spanish MEP Susana Solís Pérez (Renew Europe) has said that her interest in advanced biotechnology and ATMPs came naturally. An engineer by training, she spent 18 years in the private sector before becoming an MEP.

The upcoming revision of the pharmaceutical legislation is a perfect opportunity to spotlight the sector, said the MEP, “The opportunities are huge, but the challenges are as well,” Pérez said. 

However, the European Commission doesn’t plan to change the clinical criteria used to classify treatments as advanced therapy medicinal products (ATMPs) in its upcoming revision of blood, tissue and cells legislation, Andrzej Rys, director for health systems and products at DG SANTE, said. 

Speaking at an event, Rys said that a proposal is expected before the summer. “It is time to update this framework, so that it continues to assure that safety and quality requirements reflect the many technological developments and new risks in the field of transplantation, transfusion medicine and assisted reproduction,” the Commission official said in his prepared remarks.

EAPM Expert Panels – Challenges Ahead!!

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Despite the unique possibilities of these technologies, there are some outstanding challenges across regulatory, scientific, manufacturing, and market access fields that still hamper the ability to deliver the potential. Gene therapies display a number of specific characteristics challenging the current healthcare systems’ paradigm. They have, at present, uncertain outcomes. They are “one-off and once-only treatments,” as single treatments for chronic disease, for – at present – limited populations only, and possibly offering life-changing improvement. 

There are numerous challenges facing the sector, complicating the translation from research into patient access. The performance of ATMPs still needs to be optimised. Gene therapy has yet to deliver fully on its promises for patients. There are scientific, clinical development and regulatory issues that hamper development of the sector, including inadequate understanding of the way the products act/react in the body, the need for robust and predictable manufacturing processes that can produce products that are fit for the patient in either an individualised way or in a “very small populations” way, a strong correlation between the knowledge of the product and the safety profile and clinical benefit (including RWD in the post approval space), and the ability to reduce cost.

In contrast to innovation with new chemical entities or biologics such as antibodies and vaccines, ATMP development involves substantial scientific and technical uncertainties, compounded by limited experience with clinical and commercial use, and difficulties for SMEs in accessing funds. 

Regulatory

Legislation has evolved over two decades both to promote the sector’s potential and to safeguard the public. The basic EU rules on pharmaceuticals dating back to 2001 have been updated to cover the advancing science and technology. Under EU legislation, stem cells are categorised as ATMPs when these cells undergo substantial manipulation or are used for a different essential function. They can be somatic-cell therapy products or tissue-engineered products, depending on how the medicine works in the body.

Regulators themselves have faced difficulties in reaching decisions. The EMA’s assessment of alipogene followed protracted deliberations in which the file was examined and voted on four times, and the conventions – if not the rules – governing EMA procedures were all but thrown out of the window. The EMA rejected its approval despite a favourable recommendation by the specialist CAT committee, demonstrating the need for clarifying the relationship between Committee for Advanced Therapies (CAT) and Committee for Medicinal Products for Human Use (CHMP), and for some greater recognition that many issues in the regulatory dossier of ATMPs require specific understanding of gene and cell therapy products in addition to a robust general knowledge of the issues of traditional pharmacology. CAT members themselves maintain that the rapidly evolving field of gene therapy needs an integrated approach. 

Also to note…

ATMPs feature prominently in the reinforced EU-US collaboration on medicines, with senior officials from the Commission, EMA, and FDA acknowledging the “similar regulatory challenges on both sides of the Atlantic,” and agreeing to encourage early parallel scientific advice and to strengthen collaboration on common scientific approaches on regulation 

Additional assistance may emerge in the shape of the (also delayed) 2014 regulation on clinical trials, bringing more harmonised and swifter processes for approval of clinical trials.  And in terms of public support, despite the current complex regulatory regime there is a balance in favour, even of gene therapy, albeit laced with considerable uncertainty.

Within the manufacturing sector, there is growing interest in systems integration in production and distribution as the conviction grows that well-defined strategies will be critical for future standardisation and workflow optimisation.

Other areas of advanced investigation include small-molecule drugs that selectively control mRNA translation into proteins, plant micro-vesicles containing small RNAs in delivering and adjuvancy for sustainable cancer therapy, and developing the next generation of gene therapies, CRISPR-Cas9 technology, and engineered exosome therapeutics.

This will be an issue of engagement with EAPM and of interest to our members for the rest of the year – and EAPM has published an article, Propelling Healthcare with Advanced Therapy Medicinal Products: A Policy Discussion, which is available to read, click here.  

And in other policy issues…

EMA and EUnetHTA publish work program for 2021-2023

EMA and the previous European Network for Health Technology Assessment (EUnetHTA), which was established through consecutive Joint Actions of which the last one concluded in May 2021, started their collaboration in 2010 based on recommendations from the High-level Pharmaceutical Forum1, with the aim to harness synergies between regulatory evaluation and health technology assessment (HTA) along the lifecycle of a medicine. A first EMA-EUnetHTA work plan was established for the years 2012-2015 and a report on the outcomes of this joint work published in April 2016. Subsequently, a second joint work plan for the years 2017-2021 was agreed and a report published in June 2021. 

Parliament gives final green light to data-sharing bill

Lawmakers have approved the deal that negotiators from Parliament and Council clinched in December on the Data Governance Act, a bill that aims to boost the data economy by regulating intermediaries. The deal was approved by an overwhelming majority, 501 votes to 12, with 40 abstentions. The DGA defines the rules for trading data, includes smaller actors in the data economy, and provides a mechanism for re-using public-sector data. “Our goal with the DGA was to set the foundation for a data economy people and businesses can trust in. Only if trust and fairness are guaranteed, data sharing can flourish to its fullest potential and stimulate new business models and social innovation,” Angelika Niebler, the leading negotiator for the European Parliament, said. 

Mystery hepatitis outbreak

At least one child has died after falling ill from a mysterious outbreak of acute hepatitis that has infected children in 10 European countries, the World Health Organization (WHO) has confirmed. As of 21 April, there had been at least 169 cases of “unknown origin” around the world, the WHO said. “Cases are aged one month to 16 years old. 17 children (approximately 10 per cent) have required liver transplantation; at least one death has been reported,” the WHO said. Hepatitis is inflammation of the liver, which is a vital organ for processing nutrients, filtering blood, and fighting infections. While the WHO said that the cause of the infections was still being investigated, the UN body noted that an adenovirus infection leading to acute hepatitis was one possible option under consideration.

How the pandemic has affected women’s health

Thirteen percent of women, compared with 7% of men, also said they had to skip doctor’s visits or avoid the health care system during the pandemic “due to factors outside my control,” such as finances, transportation or a physical disability.(Getty Stock Images) The pandemic has changed the lives of people around the world, and has had a particularly unique impact on women. A larger number of women were driven out of the workforce as the country locked down, and for many, it’s been a major challenge to juggle remote work and family responsibilities during a period of economic uncertainty, limited child care options and unstable school arrangements. 

EU law change guarantees NI medicine supply 

Changes to European Union (EU) law aimed at guaranteeing the supply of medicines from Great Britain to Northern Ireland have passed their final stage. The European Council has ratified the changes, which were passed by the European Parliament last week. The Northern Ireland Protocol means Northern Ireland is still inside the EU’s pharmaceutical regulatory system. However, it gets most of its medicines from Great Britain, which is not. This emerged as one of the protocol’s major difficulties, with pharmaceutical firms warning it would lead to withdrawal of products. In December 2021, the EU published proposals which were aimed at creating something close to the pre-Brexit status quo. The EU’s chief negotiator, Maroš Šefčovič, said the changes ensured a continued supply of medicines to Northern Ireland. “We now have a lasting solution, which was delivered in record time,” he said. “I will continue to work closely with the UK government to ensure predictability, legal certainty and the prosperity of all communities in Northern Ireland.”

And that is everything from EAPM for now – a reminder, you can view the EAPM article on Advanced Therapy Medicinal Products HERE.  Stay safe and well, and enjoy the rest of the week.

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