Issue:May 2023

IMMUNOLOGY – Innovation Gathers Momentum Amid New Scientific & Technological Breakthroughs


The fields of immunology and immuno-oncology have seen some significant advances and changes throughout the past decade or more, all of which are bringing new hope to patients and healthcare systems. In the next 5 years, these advances are expected to gather momentum amid new scientific and techno­logical breakthroughs.

In particular, immunology has witnessed three major trends, each crucial to continued advancement in the field. These are the next generation of immunological treatments, new approaches to research globally, and the arrival and growing importance of biosimilars. As we look forward to 2023 developments, we can expect to see some significant results in the clinic and on the market.


The age of immunology really began in the late 1990s and early 2000s with Tumor Necrosis Factor (TNF) alpha inhibitors and vascular endothelial growth factor (VEGF) inhibitors. Products such as infliximab (Remicade®) and adalimumab (Humira®) to treat a host of autoimmune disorders and products like beva­cizumab (Avastin®) and others to treat cancer marked the arrival of this area of innovation.

The next major developments came more than a decade later with the emergence of a new generation of monoclonal an­tibodies, such as pembrolizumab (Keytruda®) and nivolumab (Opdivo®), to treat different types of cancer, bringing new ap­proaches to these difficult pathologies. Since then, monoclonal antibodies have become the top selling drugs in the pharmaceu­tical market.1

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Even more recent is the approval of several Janus kinase (JAK) inhibitors to treat a variety of chronic inflammatory disor­ders, such as rheumatoid arthritis, ulcerative colitis, and atopic dermatitis. These treatments tackle inflammatory conditions in a different way to classic treatments, offering hope of both symptom relief and slowing progression of disease.

Nevertheless, there have been some safety concerns raised with some JAK inhibitors, including tofacitinib (Xeljanz®) for the treatment of arthritis and ulcerative colitis, underscoring the im­portance of safety monitoring in late-stage clinical trials and through registries to assess their impact on a larger pool of pa­tients.


New approaches to research, both with biologics and small molecule products, have led to therapies for pathologies that pre­viously had no or very limited treatments.

Until recently, atopic dermatitis was managed with topical therapies, but research carried out by biotech and specialist pharma companies has paved the way for more holistic treatment options, including dupilumab (Dupixent®) and tralokinumab (Adbry® or Adtralza®), an injection that gained European Medi­cines Agency (EMA) approval in early 2021 and US Food and Drug Administration (FDA) approval later the same year.

The first treatment for active systemic lupus erythematosus in decades, anifrolumab (Saphnelo®), brings hope to patients suf­fering from this debilitating autoimmune disease. While used in combination with immunosuppressants, it marks a huge step forward after monoclonal and polyclonal antibody approaches proved unsuccessful.

Another disease area companies have struggled to successfully treat is Alzheimer’s disease. However, the approval of aducanumab (Aduhelm®) followed by the recent approval of lecanemab (Leqembi®) opened the door to addressing the underlying biology of the disease and slowing cognitive decline of some patients with the disease. However, concerns have been raised as to whether the benefits justify the risks, side effects, and cost of the drug.2

Perhaps one of the most prominent developments since 2020 has been in the area of mRNA research. While the best-known re­search and early success has been with the COVID-19 vaccines, companies are also targeting other viral diseases, such as the Zika virus and HIV, and several biotech companies have ongoing pro­grams focused on cancer vaccines, with a number in clinical trials. There have been some promising results with an antigen specific T cell response, including prolonged disease-free survival in some clin­ical trials.3

One key consideration with mRNA discoveries is the complexity of scaling up good manufacturing practice (GMP)-grade production, given how new the field is from a development perspective. Equally, it will be important to set up registries or long-term follow-up of pa­tient cohorts to monitor the safety of these products.

Beyond drug research, another area that has seen significant advances in recent years is artificial intelligence, in particular, AI and the Internet of Medical Things. These technologies are important for innovation because they provide insight into the different types of cells in the immunology system – their roles, their importance, how they interact with each other, and pathologies in the field of immune disorders – in a way that is difficult to observe through traditional human research. The observations enabled by these technologies provide new insights into potential approaches to treat or even prevent certain pathologies.


While many of the innovations of the past decade or more have created new hope for patients, the cost of many of these products has been an issue for healthcare systems. Pharmaceutical compa­nies have fought to protect their patents, but healthcare systems, particularly in Europe, have been keen to support the development of biosimilars. In September 2022, the EMA and the Heads of Med­icines Agency (HMA) issued a joint statement noting that biosimilars that have been approved in the EU are interchangeable with the ref­erence medicine or a comparable biosimilar.4

The UK’s National Health Service, for example, has welcomed biosimilars and the cost savings these create, noting after negotiations in 2018 that using the best-value adalimumab biosimilar product would save the NHS £300 million of its previously £400 million-per-year spending on the product.5

While there are development chal­lenges to bringing a biosimilar to market, requiring expertise and investment by the companies involved, these products are broadly welcomed, at least in the EU, and make access to life-saving treatments more affordable for countries and pa­tients. The US has been slower to adopt biosimilars, but they are starting to be seen as more attractive options by healthcare stakeholders.


The improvements in research, the ar­rival of new treatments on the market, and the use of novel technologies all pave the way for more breakthroughs around 2025. In 2021, for example, the FDA ap­proved 50 innovative drugs, offering more treatment options for patients in the US.6

Importantly, many of these products are in therapeutic categories in which there is not a huge armamentarium, such as atopic dermatitis, and in areas in which there is enormous unmet need, such as Alzheimer’s disease. Research in this ther­apeutic category is not only being con­ducted with biotech products such as monoclonal antibodies, but also with small molecules. Animal studies of neuron-tar­geted treatment based on zinc-finger DNA-binding proteins (ZFPs) were found to lower brain levels of mutant huntingtin (mHTT) protein in a Huntington’s disease mouse model and extend survival.7

The same is true in the area of multi­ple sclerosis in which one biotech leader, Biogen, which has an extensive MS portfo­lio, has been exploring small molecule treatments for the disease in partnership with other innovator companies.8

We will also see more biosimilars come to market in the next few years, in­cluding from companies that developed the originator product as they seek to pre­serve their market share. As an example, Kyowa Hakko Kirin received approval in Japan for a biosimilar of its own product darbepoetin alfa for the treatment of ane­mia associated with chronic renal failure and cancer chemotherapy.9


As developers of innovative products look to extend their research into new areas, it is important to ensure early dia­logue with the health authorities, especially during the development phase. Discussing and getting validation on the approach can help ensure development plans are in line with regulators’ expectations.

Ideally, discussions should start as soon as a company has a potential drug candidate and an idea of where they want to go with the target product profile (TPP). Given the global nature of drug develop­ment, it’s preferable to have discussions at least with the regulators in the two major regions, the US and the EU, starting with an initial meeting followed by continuous dialogue.

While there is often a belief that reg­ulators are not supportive of drug devel­opment, the evidence is to the contrary, with most regulators eager to support in­novation and help bring new products to patients in need. Whether through formal or informal discussions, regulators provide a lot of feedback and recommendations to companies that liaise with them.

The FDA, EMA, and the UK’s MHRA all have formal avenues that support de­velopment. For example, the EMA’s PRIME scheme offers enhanced interaction and early dialogue between the regulator and sponsors developing medicines that target an unmet medical need.10 FDA’s INTER­ACT is an informal meeting early in prod­uct development that is offered for programs that are neither too premature nor too advanced in development.11 In the UK, the Innovative Licensing and Access Pathway (ILAP) seeks to help sponsors bring their products to market faster by providing in-depth regulatory and other stakeholder input.12

Increasingly, companies are starting to appreciate the importance of initiating such a dialogue with the regulators and, as the health authorities place greater em­phasis on these discussions, these interac­tions are likely to increase.

Other important avenues for bringing products to the market in the coming years will be to consider pathways such as com­passionate use programs that allow com­panies to propose pre-submission use of their products for patients with serious unmet needs, such as cancer and immune disorders. Several countries in Europe have either named patient programs or in a few countries (Spain, Italy, France, and Sweden) small cohorts of patients who could possibly all be on the same protocol.

These programs not only allow pa­tients to get the help they need sooner, but are also a tool that sponsors can use to gain greater visibility for their products by physicians, patients, and key opinion lead­ers, while at the same time gathering more real-world and safety data on the product. Having real-world data will become of greater importance in future as companies not only seek to demonstrate the safety and efficacy of their product, but also demonstrate its usefulness to the health technology assessment bodies for reim­bursement.

One regulatory consideration for companies going into 2023 and beyond will be how to address the issue of the pe­diatric investigation plan (PIP). Depending on prevalence figures of disease in the pe­diatric population, there are likely to be tighter requirements with regard to demonstrating the product can be used by children under 16, whether the same for­mulation or one adapted to that popula­tion.

While this does present a constraint for companies, regulators are focused on ensuring pediatric patients, particularly those with rare or life-threatening dis­eases, have access to efficacious and safe treatments.


The year ahead is likely to bring breakthroughs in drug and biologic devel­opments. Managing the development and the regulatory pathway will require a thoughtful, preferably global strategy, fo­cusing on patient need and the expecta­tions of the health authorities.


  1. Moving up with the monoclonals, Na­ture, Sept 2019.
  2. Alzheimer’s disease: FDA approves lecanemab amid cost and safety con­cerns, BMJ, 2023.
  3. mRNA vaccines — a new era in vacci­nology, Nature, Jan 2018.
  4. Biosimilar medicines can be inter­changed, EMA, Sept 2022.­changed#:~:text=EMA_and_the_Heads_of,or_with_an_equivalent_biosimilar.
  5. After Biosimilar Deals, UK Spending on Adalimumab Will Drop by 75%, AJMC, Nov 2018. https://www.cen­
  6. Novel Drug Approvals for 2021, FDA.­ties-and-new-therapeutic-biological-products/novel-drug-approvals-2021.
  7. Treatment With Zinc-finger Proteins Shows Promise in Huntington’s Mice, Huntington’s Disease News, Jan 2023. https://huntingtonsdisease­­teins-shows-promise-huntingtons-mouse-model/.
  8. Biogen and Skyhawk Therapeutics Announce Agreement to Develop Novel Small Molecule RNA Splicing Modifiers for Neurological Disease Targets, Biogen news release, Jan 2019. news-releases/news-release-details/biogen-and-skyhawk-thera­peutics-announce-agreement-de­velop-novel.
  9. Japan approves first darbepoetin alfa biosimilar, Generics and Biosimilars Initiative, Sept 2018. https://gabion­
  10. PRIME: priority medicines, EMA.­ment/prime-priority-medicines.
  11. OTAT INTERACT Meeting, FDA.­apy-products/otat-interact-meeting.
  12. Innovative Licensing and Access Pathway.­ance/innovative-licensing-and-ac­cess-pathway.

Dr. Patrick Larcier is Senior Director at PharmaLex and has worked in drug development and regulatory affairs for 30 years, at biotech companies, CROs, and in consulting. Until April 2022, he led drug development and pharmacovigilance activities for PharmaLex France and Benelux; he now provides support for PharmaLex’s growing EU and US activities in these areas.