aking medicines tailored to the needs and characteristics of individual patients is the dream for many scientists. This kind of personalized medicine approach would provide treatment with the highest possible effectiveness and safety, and would also save money. But it requires rethinking how we make medications.
The starting point of personalized medicine can be traced to the completion of the Human Genome Project, which sequenced almost the entire human genome, in 2001. Since then, however, only a limited number of personalized pharmaceutical treatments have reached patients. Technical issues like the lack of validated genetic tests and biomarkers to predict patient responses are often cited as reasons for the disappointingly slow rollout of precision medicines.
I believe there’s another, bigger reason. The current pharmaceutical model, with its dramatically increasing drug prices, long development times, and extensive regulations, is completely unsuitable for creating precision medicines. On average, it takes about three years from the time a company submits a new drug application to the Food and Drug Administration or the European Medicines Agency before it reaches patients. That is much too long for a medicine tailored to a specific patient with a life-threatening disease.
A major obstacle posed by the current regulatory system is the lock-in of technology it imposes early during development, technology that is contrary to personalizing a product for an individual’s needs. As the approval process is currently structured, precisely the same product must be used during preclinical and clinical development, and the marketed product must also be the same formulation. Any change in the product or the way it is used and all the testing must be repeated, adding years to the process.
Drug prices are increasing dramatically, especially among the kinds of precision medicine drugs used for some so-called orphan conditions. Take Glybera, developed to treat lipoprotein lipase deficiency, a rare but serious condition caused by a defect in a protein needed to break down fat molecules in the bloodstream. This drug contains billions of viruses that have correct copies of the lipoprotein lipase gene. Treatment with the drug, which costs 1.2 million Euros ($1,343,100), has only a minimal clinical effect. Treatment with one of 50 drugs for very small patient populations currently approved by the FDA costs between $70,000 and $130,000.
The current pharmaceutical system is too complicated, too expensive, and too inflexible to enable precision medicine. We need innovative approaches and business models to create a sustainable health system that includes affordable precision medicines for those who need them.
In a recent article in the journal Nature Biotechnology, my colleagues and I from Utrecht University in the Netherlands describe “bedside biopharmaceuticals” as a way to bring drug development and production as close as possible to the patient. When production and treatment are under the responsibility of the same institute, no marketing authorization is needed. This approach bypasses the pharmaceutical industry, the main driver of soaring drug costs.
Personalized medicines will most likely initially focus on biopharmaceuticals such as proteins, peptides, and monoclonal antibodies. These can be adapted to an individual patient’s needs with relative ease.
For a single patient, doses of biopharmaceuticals vary from micrograms per kilogram of body weight to milligrams. Providing bedside production of a biopharmaceutical product, then, would mean generating just a few grams of it. Relatively small-scale culture and purification units would be adequate to produce the majority of products needed as precision medicines.
Drug production at that small level is common practice in the pharmaceutical industry during the discovery and early development phase of biopharmaceuticals — meaning the technology is available for production in hospital pharmacies. The costs for biopharmaceuticals produced in a hospital pharmacy setting are likely to be 2,000 Euros per gram ($2,238). With current biopharmaceuticals costing up to 500,000 Euros per gram ($559,625), production in hospital pharmacies makes sound economic sense.
To demonstrate the feasibility of this concept, my colleagues and I set up the production of precision medicines for the treatment of two orphan diseases in the pharmacy of a large academic hospital in the Netherlands. We chose biopharmaceuticals, like the enzymes used for enzyme replacement therapies for Gaucher disease, Pompe disease, and others, because these types of drugs are relatively safe. Only two factors determine the safety of a biopharmaceutical: its potency or strength and its purity. These characteristics can be easily controlled for and tested.
In our proof-of-principle demonstration, we will use our hospital’s pharmacy, which has the equipment and expertise to make safe, high-quality biopharmaceuticals. We plan to evaluate the safety and effectiveness of these individually made drugs in clinical trials. One of the trials will be performed in the developing world, since the vast majority of children with this lethal disease cannot get access to treatment because of the high cost of the drug. We plan to donate the cloned drug, the production technology, and all of the clinical data to the World Health Organization so it can continue local production of the drug in the developing world.
If the pilot is successful, we will branch out to include less-experienced pharmacies. We will develop for them a closed, integrated, easy-to-operate machine capable of producing grams of biopharmaceuticals of high and reproducible quality. We already have a name for this machine: the Bionexpresso.
Bedside drug development makes personalized medicine with biopharmaceuticals scientifically and economically possible. It brings pharmaceutical development back to its basics, because it will be driven by medical needs more than financial rewards. It will be good for doctors and pharmacists, who will get back their traditional roles in health care. Most of all it will be best for individual patients, who would be completely involved in the decisions about treatment.
Huub Schellekens, M.D., is professor of pharmaceutical biotechnology in the Department of Pharmaceutical Sciences at Utrecht University in the Netherlands.