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Researchers Devising Creative Solutions to the Challenges of Developing Oral Biologics
Posted on March 28th, 2019 by Elia Lima-Walton, MD in Pharma R&D
Many biologic drugs, which are protein-based drugs derived from living organisms, have practically become household words in recent years as the airwaves tout names like Humira, Enbrel and Neulasta. Biologics treat diseases ranging from Crohn’s disease to rheumatoid arthritis to cancer, and have become an important market in the pharmaceutical industry. Although many of these drugs are relatively new, the very first biologic, insulin, was introduced in 1982.
While popular, biologics are unfortunately inconvenient to administer because they typically must be taken via injection. Most people consider pills vastly preferable since they are a quicker, less awkward and less painful way to take a drug. As a result, oral biologics have become a new kind of holy grail for many pharma companies, but the task has proven to be a major R&D challenge.
According to Cynthia A. Challener of Pharmaceutical Technology, the main reasons why it is so difficult to successfully deliver biologic APIs orally are:
- The large size of biomolecules makes it hard for them to diffuse across the epithelial layer in the GI tract
- Biologics are susceptible to degradation due to the acidic environment of the gut and the enzymatic activity in the intestine
- The degradation issues combined with poor absorbance results in low bioavailability (and if you try to counter that by raising the dose, then side effects become a bigger problem)
An Injection in Pill Form
But what if the solution was to create a pill with a tiny robot in it? And the tiny robot had a needle, and used that needle to inject the patient internally? Does that sound crazy? Maybe, but that is very close to the solution that Rani Therapeutics has been testing with significant success.
Natalie Grover of Endpoints News explains Rani’s oral biologic like this: “The capsule has an enteric coating that protects it from the acidic ambience of the stomach, and once it moves into the intestine and pH levels rise, the coating dissolves and a chemical reaction takes place which inflates a balloon. Pressure in the balloon pushes a dissolvable microneedle filled with the drug into the intestinal wall.”
The RaniPill has already been through 100 preclinical studies, including animal trials and a recent study in healthy humans for assessing the product’s feasibility. Researchers at MIT and Novo Nordisk have also been working on their own “needle in a pill” device called Soma, so it’s definitely an exciting time for weird-but-fascinating robotic pills!
Other Outside-the-Box Solutions
Biotech Primer reports that other kinds of oral biologics are in the works as well: “Applied Molecular Transport is using a protein scaffold adapted from pathogenic microbes such as salmonella, which colonize the gut by secreting immune-crippling proteins into our body,” writes Emily Burke, PhD. “Proteins from these ‘gut bugs’ work by tricking the intestines into absorbing toxic proteins in the same way that they absorb nutrients from food. Applied Molecular Transport scientists have tweaked these microbial proteins to carry a therapeutic payload, rather than the toxins.”
To get past the challenges of delivering the proteins, Vancouver-based enGene has a unique approach that is designed to deliver a gene (using nanoparticles to encase the gene) that instructs the gut itself to make the therapeutic protein. “enGene is currently using this platform in the preclinical development of the anti-inflammatory protein IL-10, for the treatment of inflammatory bowel disease,” notes Burke.
While all of these pills, platforms and approaches have hurdles to get over yet, innovative drug developers are clearly on track to make oral biologics a reality for millions of eager patients.
Elia Suzette Lima-Walton, MD is part of the Elsevier Content Transformation & Health Analytics team in her role as a Clinical Knowledge Representation Specialist. She applies her clinical knowledge and analytics experience to support clinical ontologies, Smart Content applications, precision medicine, clinical decision support and inference products.
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