Bio-medicines and biologics have been an integral part of our lives for decades, but their constant evolution means that todays’ biologics are revolutionizing medicine. In 2016, they already accounted for 25% of the US$232 billion pharmaceutical market and the trend continues to accelerate.
New biologic therapies have revolutionized cancer treatment and offer hope to many patients who previously had no effective treatment options for their disease. The advances are convincing: take breast cancer for example, the average five-year survival rate is 90%, up from close to 75% for women diagnosed in the mid-seventies, and the average 10-year survival rate is 83% thanks to prevention and new biologic therapies.
Biologics - such as antibodies, proteins or enzymes - are large molecules, often 200 to 1000 times the size of “classical” small molecules in chemical drugs. They are engineered by nature or by scientists, and can only be made using living cells in a fermentation process that is not unlike brewing beer. They have been largely used in vaccines and to mimic insulin, significantly improving the lives of people living with diabetes since the 1990s. People with rare genetic diseases have also found hope thanks to enzyme replacement therapy pioneered by Sanofi Genzyme at the beginning of the 1980s.
"For insulin, as for substitution treatments in rare diseases, we compensate for the proteins’ deficiencies by providing a replica that is almost identical to the human protein,” explained Carole Fages, Head of Platform Management Office, Biologics Development at Sanofi.
"This precision power of biologics is also a huge benefit for the patient,” said Fages. “With biologics, side effects are reduced considerably such as hair loss in cancer for example that can be particularly stigmatizing and distressing for patients in chemotherapy."
Not only have new biologic therapies revolutionized cancer treatment, they are also becoming increasingly important as the most advanced therapies for other serious diseases, such as Crohn's disease, ulcerative colitis, rheumatoid arthritis (RA) and other autoimmune diseases.
Brendan O’Callaghan, Global Head Biologics Platform, Sanofi Genzyme, knows all about the benefits that biologics can bring to patients. His mother suffered from RA for more than 30 years and was eventually wheelchair-bound. Through the years, she tried a plethora of different treatments, but none brought true relief. Unfortunately, she did not live to benefit from biologics, but O’Callaghan’s brother and sister, who also suffer from RA, do not have to share the same fate:
“My mother desperately tried to rid herself of the pain, the discomfort and the immobility that the disease brought on her. Unfortunately and sadly, she died in 1997, which was a few years before the first biologic treatment for RA came on the market. So she never got the opportunity that those treatments have to really change your life. My siblings do have symptoms but nothing like what she had to go through. They don’t have the joint deformation, the disability, or the pain.
“I saw the devastation that that disease can bring to patients and the struggle that they have to just be normal. Every patient you talk to just wants to be normal. They don’t want to be sick. And you can see the power of biologic treatments to make that happen.”
In line with their growing importance, the number of approved biologic drugs is increasing, with 10 new medicines approved in the European Union and the United States in 2017 out of a total of 92 and 46 new medicines in those regions, respectively, according to Fortune. It is estimated that in 2015, 325 million patients worldwide had already benefited from biologics.
Sanofi's portfolio has been reoriented towards biologics, and today, they account for half of the company’s medicines.
Industrial expertise is crucial
The efforts and progress of research would be in vain if the medicine was unavailable due to difficulties in manufacturing. Biologics manufacturing is a complex process since even minor alterations in cell growth conditions may lead to the differences in the end product, which eventually may impact the product safety and efficacy. Therefore, strong expertise and understanding of biology and bioengineering, equipment design, cell genetics, and cell culture technology are the key for successful design and manufacturing of biologics.
For biologics, "the process determines the product" because the process, defined at the very beginning with a cell line (a single cell - human, animal, or plant - that has been adapted to grow continuously in the laboratory and used in research), is maintained throughout the manufacturing cycle. The reproduction of cells - the living organisms that produce the antibodies - can be impacted by the slightest variations - changes in external temperature, salt or pH concentrations. The environment must be constant and the profile is constantly monitored, which today requires human intervention.
In Sanofi’s factories of the future, a growing reality, these human interventions will be extremely limited. State-of-the-art analytical techniques will control all stages of manufacture to predict or avoid variation for improved performance and quality of biologic medicines.
In theory, almost all diseases could be cured by biologics one day; researchers at Sanofi work every day with this in mind.
Developing the optimum device to deliver biologics
Biologics are tremendously efficacious molecules that now enable us to treat diseases that we previously struggled with, but their size - 200 to 1,000 times larger than chemical molecules - means they cannot be swallowed, obliging patients with a chronic disease to inject themselves on a regular basis. At Sanofi, the Device Development Unit team work closely with patients not only to get their input on how to design the optimum delivery device but also to gather information through mobile phones around how patients manage their medicines to develop the best experience possible. “What really defines our entire team is trying to figure out how we can help people do something they don’t necessarily want to do, like inject themselves, how we can give them the information they need to use their medicine more effectively and hopefully improve their quality of life,” says Jim Collins, Head of the Device Development Unit.
The ABC of biologics
There are two categories of biologics, also known as biotherapies or biotherapeutic:
- Therapeutic proteins (hormones, cellular growth factors, enzymes, etc.) are usually designed to replace a missing protein, for example insulin in people with diabetes.
- Therapeutic monoclonal antibodies recognize a unique target and have a specific task. For example, they bind to a protein on the surface of a cancer cell and guide the immune system to destroy the tumor.
Novel generations of biologics include fusion proteins, a combination of therapeutic proteins and monoclonal antibodies, antibody drug conjugates, which use antibodies as a vector to deliver the drug at the site of action, and multispecific antibodies with multiple mechanisms of action in a single molecule.