Advanced therapeutics: The next generation of medicines

17 Nov 2022

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NIBRT’s Killian O’Driscoll looks back at how far drug development has come and what the future holds for the pharma sector.

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The impact of innovative medicines on human health has been one of the great achievements of humankind. Once common and often fatal diseases such as smallpox, diphtheria, typhoid, polio, rubella, measles and mumps are now successfully managed and often effectively eradicated.

In 1982, a new wave of innovative medicines was launched with FDA approval of the first biotech drug in the US, a genetically engineered version of human insulin.

Since then the biotech industry has grown rapidly and in 2021, the FDA approved its 100th monoclonal antibody therapeutic. The global sales of biopharmaceuticals are now more than $300bn, with a compound annual growth rate of 12pc and with approximately 60pc of therapeutics in development being biopharmaceuticals.

Of course, biotech innovation featured prominently in the public conscious as the world waited anxiously for the development of vaccines and anti-viral treatments during the Covid pandemic.

This culminated with the historic achievement of creating the first batch of a candidate mRNA vaccine within an incredibly short timeframe from when the SARs-CoV-2 virus was first genetically sequenced.

Then a 50,000-step process for building the mRNA vaccine with multiple supply chain and manufacturing innovations was created. Remarkably, within 18 months more than 7bn doses of various vaccines had been distributed globally.

Notwithstanding these achievements, much remains to be done. For example there are more than 7,000 rare diseases affecting more than 300m people worldwide with just 5pc of these diseases having effective treatments.  So, what are the new therapies coming through the clinical pipeline?

The pace of change

Over the last 10 years the impact of biotech medicines has mainly been driven by monoclonal antibodies and recombinant therapeutic proteins. However, new highly innovative medicines are now rapidly coming through the pipeline creating an unprecedented diversity of therapeutic modalities.

In accordance with the PhRMA report, Innovation in the Biopharmaceutical Pipeline in December 2021, there were more than 12,600 projects in clinical development with approximately 50pc being for small molecule chemistry products and 50pc being biopharma products.

These projects were distributed across many therapeutic areas, with a significant majority focused on oncology (50pc), and then autoimmune diseases (11pc), central nervous system (10pc), infectious diseases (7pc).

Another 20pc of these projects in clinical development focus on monoclonal antibodies. This includes new more complex multi-specific antibodies and antibody drug conjugates (ADCs), which use highly selective monoclonal antibodies joined to other agents such as chemotherapy drugs to target specific cells such as tumours, while sparing nearby healthy cells.

Another 4.3pc are cell therapy projects, in which healthy, functioning cells are themselves the therapy and introduced to treat a disease or condition in which the patient’s cells are damaged or diseased.

Of particular interest is gene-modified cell therapy (348 projects, 2.7pc), in which a functional gene is introduced into a cell-based therapy. For example, chimeric antigen teceptor T-cell (CAR-T) therapies have proven to be remarkably effective at not just treating but effectively curing certain previously fatal blood cancers.

This type of personalised medicine involves extracting a patient’s blood cells to purify their T-cells, which are then genetically engineered and reinjected back into the donor patient. The engineered T-cells then activate that individual patient’s immune system to specifically target the particular cancer.

Further exciting classes of therapies in development include gene therapies (281 projects, 2.2pc), in which a patient’s genes are modified to treat or prevent a disease. RNA therapeutics, like antisense drugs that block messenger RNA translation and thereby prevent the production of certain disease-associated proteins.

Oncolytic viruses, in which tumour-seeking viruses infect tumour cells and replicate themselves until the cells burst, releasing markers that allow the cancer to be recognised by the immune system and an immune response is then mounted against the cancer. Also 2021 saw the first deployment of gene editing (CRISPR-CAS9) in-vivo phase 1 trial.

The long, winding road

The road from discovery of a new medicine through clinical trial and finally into patients is a long and winding one. On average it takes $2.6bn and more than 10 years to develop a new medicine, with only 12pc of products entering clinical trial eventually become licensed products.

The level of risk and investment required to overcome these odds is very significant. For example, Eli Lilly spend 25pc of net sales on research and development and have spent billions of dollars over 30 years on research for treatments for Alzheimer’s disease.

This diversity in the biotech pipeline is driving fundamental changes in manufacturing facility design, operations and supply chain with a focus on flexible and agile facilities with the ability to manufacture multiple products.

Digitisation has potential to be a key enabler of a manufacturing competitive advantage, though significant barriers remain – in particular, access to end-to-end high quality data management from research to manufacturing operations.

To remain competitive there is continued demand for new efficiencies, improved quality and cost reductions in manufacturing processes. Key trends, many of which rely on vendor innovation, include:

  • More flexible, modular multi-product facilities
  • Further adoption of single-use systems at clinical scales and commercial scales
  • Steady increase in expression titres and purification yields with incremental improvements in host cell lines, culture media, expression systems, vectors, promoters, etc
  • Continuous processing, including upstream perfusion and downstream chromatography
  • Implementation of industry 4.0 and digitalisation technologies with a particular focus on automation and data analytics

Biopharma manufacturing is energy and water intensive, which needs to be balanced with an ever-increasing focus on sustainable operations. Many firms are already taking the lead on this for example, Eli Lilly, while celebrating its 40th anniversary in Kinsale, also opened the single largest solar farm in Ireland. Johnson & Johnson is also progressing its global plans to source 100pc of its electricity from renewable sources by 2025.

As always, there are multiple external factors that will potentially impact on the ability to bring new medicines to market including Covid-19 variants, international monetary and fiscal policies, global supply chain challenges, and geo-political developments.

Nonetheless, despite these considerable challenges the biopharma pipeline has never been as robust and diverse. If the rate of progress continues, many of the most debilitating diseases which impact our quality of life today may effectively be addressed within the next decade.

By Killian O’Driscoll

Killian O’Driscoll is the chief commercial officer of NIBRT, the National Institute for Bioprocessing Research and Training.

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