Biologics are a class of medications made from living cells that are engineered to target specific disease-causing proteins and cells with a high degree of specificity. Some biologics, such as T-cell engagers, can be used to direct the body’s immune system against disease-causing cells. Because biologics are highly specific and highly engineerable, can be designed to work through multiple mechanisms of action and often stay in the body longer, they play an important complementary role alongside another major drug modality: synthetic small-molecule drugs, which are typically taken as oral pills.
“Biologics add to our ability to treat human health because they leverage a very natural mechanism that all of us have, which are antibodies,” explains Navin Rao, Ph.D., Global Head of Immunology Discovery at Johnson & Johnson. Antibodies are proteins produced by the immune system that protect the body from pathogens like viruses and bacteria. Biologics harness the power and specificity of antibodies in therapeutic ways to treat disease.
“Biologics are manufactured in living cells and purified from there—like little living factories,” Rao says.
Vaccines, insulin injections and gene therapy are all examples of biologics. But when scientists and physicians discuss biologics, they’re often referring to monoclonal antibodies, adds Rao. These treatments have been a game changer for patients, “helping them reclaim their life in many ways.”
Biologics have long been a key focus area for Johnson & Johnson, and the company has developed biologic medicines for a number of therapeutic areas, including oncology, immunology and neuroscience. A state-of-the-art facility in North Carolina is currently under construction to expand the company’s portfolio and pipeline of biologics.
Here’s what to know about how biologics work and what diseases they treat, as well as the challenges associated with producing them.
How biologics work—and the diseases they treat
Biologics are administered to patients either intravenously or subcutaneously via injection; the mechanism of action depends on the specific drug and the disease target associated with the medical condition. Generally, biologics target specific disease-associated proteins and block signals that cause inflammation and tissue damage. They can also eliminate abnormal cells driving the disease.
Take, for example, interleukin-23 (IL-23), a type of protein that at high levels causes inflammation in the body and plays a major role in the development of autoimmune diseases such as inflammatory bowel disease, psoriatic arthritis and plaque psoriasis. Targeting and blocking IL-23 at its site of production with a biologic is the best way to suppress these conditions, and a specific monoclonal antibody drug does exactly that, explains Gabriel Cheung, Ph.D., Global Head of Biologics Discovery at Johnson & Johnson. “It basically binds to IL-23, blocking that inflammatory response in autoimmune disease patients,” he says. In other words, Rao adds, “you’re essentially shutting off the fire where it’s occurring.”
Johnson & Johnson has also developed a biologic to treat generalized myasthenia gravis, a rare autoantibody-driven disease. The medication works by decreasing levels of the disease-causing proteins in patients.
Another class of biologic, known as a bispecific antibody, is able to recognize and act on two different disease-associated targets at the same time in one drug. A bispecific antibody developed by the company, for instance, treats non-small cell lung cancer by targeting two important signals that tell the cancer cells to grow; the antibody is designed to block these signals and activate the body’s immune system to attack and kill the tumor cells. The medication is also being evaluated for the treatment of head and neck cancer and colorectal cancer.
Biologics have the potential to help patients control their diseases, eliminate symptoms, minimize flare-ups, improve their quality of life and reduce the need for surgery, hospitalization and other more invasive treatments. The exact patient experience varies by individual disease and medication.
Before biologics, patients and doctors had “very few choices” to treat certain diseases, Rao says. Patients were typically given high-dose steroids or chemotherapy, which caused many side effects. “Biologics really have changed things for patients,” he says.
Why are biologics more complex to produce than conventional medications?
Conventional medications are synthetic, made from a precise combination of various chemicals, while biologics come from living organisms. This makes biologics more complex to produce, says Rao.
“It comes down to the fact that you can control things a lot better when you’re working with chemicals,” he says. “But once you start talking about the living cells as factories, it’s a different level of complexity.”
To produce biologics, scientists start by identifying the specific disease pathway to modulate to fight a disease, says Cheung. They then engineer the specific properties of an antibody with the necessary characteristics to specifically engage the disease-associated protein target. “That optimization piece, leading to the desired drug-like properties and desired functional activity of a biologic, is extremely time-consuming but necessary,” he says. This step often takes the longest time in the biologics drug discovery life cycle.
Once an optimized antibody molecule has passed a long list of critical requirements, including attributes that are important to produce these drugs, it is then transferred into the hands of manufacturing, Cheung says.
Each of these steps must be thoroughly controlled to ensure the drugs are reproducible, Rao says, “and that every patient is getting the same thing, whether they’re taking that drug today, tomorrow or 10 years from now.”
Biologics are typically shipped and stored under controlled temperatures and other conditions before they reach patients.
Biologics in the pipeline at Johnson & Johnson
Johnson & Johnson is conducting research on different disease pathways and potential biologic medications that could treat more patients, Rao says. The “next wave of innovation” is multi-specific biologics, he says, which target several pathways in the body to treat complex diseases.
“We are already seeing the life-changing impact of these more complex multi-specific biologics in oncology, and we anticipate rapid expansion of the application of these drugs to disease areas with high unmet medical needs,” says Cheung.
The goal is to help more patients achieve remission for their disease, and biologics help make that possible.
“We will continue to explore the frontier,” Cheung adds. That includes examining improved design of biologics, incorporating artificial intelligence to improve design and optimization, better understand the disease biology to target the most relevant proteins and expand the impact for patients who do not currently have options. “Patients and disease biology will drive how far we go or how complex we need to go,” says Cheung.
