In 2016, one third of all new Food and Drug Administration (FDA) approvals were classed as a new biological entity. In the same year, European Medicines Agency (EMA) authorized 27 new active substances with 12 (44%) being a biopharmaceutical.
Undoubtedly, one of the key growth areas in pharmaceutical research is in the study of biologics, designed to meet unmet clinical needs. In fact, according to EvaluatePharma, biologics are set to contribute 52% of the top 100 product sales by 2022.
Here we look at the contributing factors of growth and speak to industry expert, Dr Kirsty Harper who explains her work in biological product development and bringing the wider scientific community together.
1. Strong results in regulatory approvals
In recent years, steady investments in Research and Development (R&D) have produced strong results in regulatory approvals. Since 2013, the FDA has approved a record 169 new molecular entities and biologics license applications. This is the strongest four-year performance of the new millennium. Similar success has been reported by the European Medicines Agency (EMA), which shows that improvements in R&D productivity are global.
2. Growth in the pre-clinical setting
The total number of molecules in development has grown consistently and as a result, the largest growth has been in the nonclinical development setting. This can be attributed to a number of factors, one of which is a strong and steady financing of biotech companies - many of which have early stage molecules. Subsequently, this investment has contributed to an upswing in new potential biological products. Additionally, there are a number of upcoming patent expirations and these looming deadlines are driving the market's demand for new and profitable treatments to replace those coming off patent.
Perhaps the largest contributing factor of growth in the preclinical setting stems from pharmaceutical companies’ ongoing needs to strengthen clinical development pipelines to address the demand for new medicines. These medicines are needed to treat diabetes, cancer, and other illnesses responsible for a large portion of global healthcare spending. Nevertheless, biosimilars still continue to be a challenge for the pharmaceutical industry - similar biological products are easier to replicate and less expensive to develop, which increases competitiveness in the market.
3. Leading therapeutic areas
With the ever-growing sophistication in the development of therapeutic products, driven by technological advancements to treat human disease, researchers have a better understanding of the biological mechanisms and the effects of therapeutic intervention. The main therapeutic areas of growth in biopharmaceuticals continue to be oncology and hematology, along with neurology and infectious disease.
4. Immunotherapy focus
Decades of research has led to an increase in collective understanding of the immune system as well as an improved understanding of its variability within and between species, aiding drug developers in translating learnings from the different phases of therapeutic development and laying the foundation for further advancements in immunotherapy. With improved immunotherapy comes curative drugs and cell therapies that turn on and off the immune system to help overcome the challenges of current unmet clinical needs.
Immuno-oncology research in particular is being powered by the success of new biological products. The drugs in this area are very potent, hence they are effective for treating cancer. However, the potency is such that making them safe is a crucial element. One area that can help increase the success rate of oncology research is choosing the right animal model at the very start of discovery. The ability to research and leverage this earlier work can have a dramatic effect on the time, resources and dollars put into the research.
5. Huge potential for safe and effective vaccines
Effective vaccines and vaccination campaigns can virtually eliminate diseases in a population. Many more diseases are now decreasing worldwide thanks to these measures. Along with infectious diseases, there are also huge growth potential opportunities for vaccines in other areas - for example in treating chronic diseases, cancer, and weight disorders.
However, there is no “one size fits all” approach for developing vaccines safely, especially for those that are biotechnology-derived. Making sure vaccines are both effective and safe raises a series of immunology-related challenges, that are of key interest to many working in the field today.
6. Developments in cellular therapeutics
CAR-T cell therapies are a good example of new and exciting immunotherapies. Similar to drugs targeting Checkpoint inhibitors (CPIs), CAR-T cell therapy attempts to boost the immune response. T cells require two signals to become activated. CAR-T cells are engineered to provide the first signal which targets tumor cells, for example, enabling more efficient targeted T cell activation. The use of CAR-T cells has led to some amazing curative treatments for certain lymphomas and other diseases such as leukemia.
7. Monoclonal antibodies as a critical component
The use of monoclonal antibodies (mAbs) as reagents has played an important role in the advancement of basic research, diagnostics and product development and has delivered huge patient benefits across a wide range of therapeutic areas. Moreover, technologies such as antibody phage display have expanded the available options to generate novel mAbs, in particular human or humanized mAbs for therapeutic purposes such as antibody drug conjugates (ADCs). An ADC molecule, consisting of a monoclonal antibody conjugated with highly cytotoxic small molecules through chemical linkers, is an emerging technology used in cancer chemotherapy. These ADC-based cytotoxic agents have shown vastly superior therapeutic applications compared to their free counterparts for treatment of a wide range of cancers. However, there are likely to be regulatory challenges in demonstrating adequate quality, safety and efficacy of the final ADC and a case-by-case approach will be needed to determine the most suitable pathway.
8. The use of pharmacodynamic endpoints and biomarkers
The successful development of molecules depends greatly on detailed understanding of the underlying biological processes as well as their pharmacological action. Therefore, researchers are now applying predictive biomarkers of pharmacological action routinely not only during clinical development but also in the preclinical studies. As the mechanism of action of the drug becomes more complex, the pharmacodynamic endpoints and biomarkers are no longer “nice to have” extras on non-clinical safety studies but pivotal for non-clinical safety data interpretation and the design of clinical studies.
9. Involvement of a strategic CRO
Biotechs and pharmaceutical companies are more driven than ever to bring new therapies to market successfully. In doing so, they are turning increasingly to contract research organizations (CROs) as strategic partners. Since the 1990s, the levels of outsourcing to CROs has increased significantly. As the volume has grown, the nature of the relationship has shifted too--from a tactical relationship to a more strategic one. As opposed to tactical outsourcing that involves employing CROs on single studies and using a variety of CROs for different drug development services, strategic outsourcing involves forming stronger, deeper relationships with large global CROs that offer a variety of services and have the experience to provide consultation on issues including study design, protocol development, study implementation, and scientific data interpretation, as well as regulatory interactions and submissions. Strategic outsourcing also often involves higher levels of integration of the CRO and study sponsor’s teams, as well as governance structures and metrics that assure quality service and science. In short, the trend of strategic outsourcing has reached a mature stage in which research sponsors and CROs are consistently partnering to improve R&D productivity.