We have plenty of prescription medications available to us but their efficiency is limited by, among other things, our body’s tendency to reject foreign entities
On any given day almost half the US population is on prescription medication according to a 2019 publication from the National Center for Health Statistics; still more take over the counter medications. In fact, you’d be hard pressed to find a person who has never taken any medication at all. It’s hardly surprising then that the revenue share of the North American pharmaceutical market last year was almost $590 billion (48.9% of the global, staggeringly large more than $1 trillion market).
Last year, the FDA approved a record number of new drugs (59; the 5-average is 43), of which 58% were orphan drugs — those that the developers are reluctant to pursue because of limited financial gains thanks to a very small number of people who will use them, such as in the cases of rare diseases.
Despite the availability of medicines (let’s put aside the issues surrounding accessibility, for now), it’s difficult finding a person who has never complained about the poor effectiveness of a medication they’ve taken. Why is this? Why is our “after-medicine” moment rarely like the one projected by people in the those medicine advertisements?
It’s complicated, so let’s take a reductionist approach
When drugs are designed, and clinically tested, and approved, they have gone through a rigorous process of evaluation to determine appropriate dosages so, for the most part you are going to get the advertised relief. But, because of losses along the way to get to the relevant part of your body, often the prescribed and recommended doses while safe, might be more than is really necessary.
Consider the journey of the almost panacea-like aspirin. You pop the pill, and it makes its way down your gullet, into your stomach, then intestines and liver from where it gets out into the blood stream and spreads across every part of your body that has access to blood.
At every step, the aspirin encounters a new environment and it has to survive that and make it to the part of your body that’s waiting to get some relief. In the process, that 80 mg aspirin is also being distributed to other parts of your body so if you’d taken it to relieve an ache in your knee, that knee is going to get less than 80 mg. In fact, because of the complexities of biology (and chemistry), depending on how a drug is administered (intravenous, oral, topical, etc) and the drug’s desired destination, sometimes vanishingly small amounts of the drug are finally available at the destination.
Thinking outside the box
Not much has changed in the last century in terms of workflow in developing new drugs. Biologists, pharmacologists, immunologists — pretty much all the -ologists related to the life sciences, and chemists, arduously tease out and refine systems that result in a new drug. According to a 2016 study from the Tufts Center for the Study of Drug Development at Tufts University, the cost of getting a new drug to market is almost $3 billion, and the process takes an average of ten years. That’s a lot of money, and a lot of time.
Contrast the development of one drug, to the design and deployment of a Mars rover — NASA’s next flagship Mars mission, the Mars 2020 rover to be launched next year will cost up to $2.5 billion. Work on the rover began in late 2014.
While this kind of contrasting might seem like comparing apples to oranges, it has led researchers to explore new methods to improve the efficiency of existing medicines — if you’ve spent $3 billion developing a new drug, why not make it an efficient one?
Work from Professor Samir Mitragotri’s lab at Harvard University has led to some novel approaches to making the process of drug uptake much more efficient. In fact, one of the novel methods results in a 30-fold efficiency over traditional methods of drug delivery both in in vitro systems and animal models — where less than 1% of a drug was available to the lungs, now 30% is available. This method involves attaching a critical concentration of drug molecules to a subject’s previously harvested red cells. These modified cells are reintroduced in the subject, and by simple principles of physics the drug is released into the lungs: since red cells have a smaller diameter than capillaries they get physically distorted as they course through the capillaries, and in the process the drug molecules get dislodged and become freely available to the lung tissue.
Blending biochemistry/biology and engineering, Mitragotri’s lab has also developed a method to use sound to open pores on the skin to deliver drugs; capsules containing microdiscs of insulin for oral delivery; liquid salts to break biofilms that prevent drugs from reaching target areas; and a method to put “backpacks” of drugs on macrophages so that these cells that are normally recruited to clear infections might now also be candidate drug-vehicles for treating a variety of diseases including cancers.
Whether it’s modifying a patient’s cells with a hitchhiker drug that reaches its destination more efficiently, or designing an altogether new way to deliver a drug, it’s clear that these new approaches and others that are still to be discovered/invented are going to be pivotal in making medicines more effective for a patient.
This outline is an off-shoot of Professor Mitragotri’s recent talk at a Tilde Cafe event that can be viewed here.