Beating Natural Selection: Bending the Drug Development Cost Curve

On the blog, In The Pipeline, Derek Lowe’s post on Pfizer’s spiraling research and development costs and stagnant drug output illustrates the predicament the pharmaceutical industry faces in the near future. He cites a recent article in Nature by Robert Munos on the reason for this. Munos lays out how the pharmaceutical market has dual problems of development cost and petering innovation which both hobble giants like Pfizer and small start ups. Through research, he shows despite start up companies innovating more efficiently, they still fail due to pinning their hopes on one drug because of the enormous development costs. On the other hand, large companies, due to short sighted leadership, have stifled innovation to capture short term gains, by forcing researchers to make “me too” blockbuster drugs. Both modes of operation are combining to slowly box the pharmaceutical industry into competing over a few blockbuster drugs, killing innovation and dooming the industry to a slow death. This obviously needs to change. Munos writes that a paradigm change is needed to break this deadlock. While Munos offers good solutions, none of them offer an easy path to breaking the near term deadlock.

Unlike Munos, I believe the solution to the industry deadlock lies partially in technology. A decrease in development costs would enable research and development of more drugs, increasing the likelihood of having a blockbuster drug. However, current methods make multiple drug development untenable for smaller start up companies. Thus, a method of drastically reducing the costs of development while combining the innovation drive of smaller start ups can break the deadlock.

The main reason for spiraling development costs lie in the difficulties of properly ascertaining how a researched drug will affect the patient. The cost drivers are the enormous amounts of time needed to both predict drug reactions and wait for drug reactions during trials. Currently, trial and error is needed for newly researched molecular entities to see how the compound will affect a patient’s body. However, the understanding of biology and chemistry has progressed far enough to predict with considerable accuracy how a compound will affect a human body’s systems. Unfortunately, geometry of the compound is needed to predict the reactions. Currently, the only way to ascertain this is to crystallize the molecule and scan or bombard the crystal with EM radiation. The crystals must be perfect to allow accurate readings. Formation of these crystals in a gravitational environment is still more art than science, and takes months many times yielding no usable crystals.

Even with compounds with known geometries, animal clinical testing for certain diseases takes up large amounts of time. Due to the huge number of variables present in a biological system, clinical tests are often iterative, with incremental improvements being made on the compound to mitigate undesirable side effects. Time is very valuable, as competing companies have parallel development efforts to reach lucrative markets first. Under the present paradigm, there is no way of significantly decreasing the time compounds take to affect complex biological system.

Fortunately, there is a solution to this. The microgravity environment of space accelerates cell division, muscle and bone atrophy. All complex organisms have higher stress levels in the low gravity environment. Also, since natural convection is diminished greatly, perfect crystalline structures of any complex compound can be made. These advantages can reduce downtime, thus lessening costs of drug development.

The use of the microgravity environment can be integrated into the existing development structure, used to accelerate specific parts of the development process. For example, a company can send up complex molecular solutions to create crystals in space, retrieve the finished crystals, and analyze them on Earth to get structures for the molecules. Also, companies can use the microgravity environment for animal trials, taking advantage of increased cell division, higher stress levels, and/or accelerated muscle atrophy to shorten the time the drugs take to act.

The entire orbital infrastructure would be automated. The equipment for this type of testing already exists, commonly used by NASA for biological experiments. No manned presence would be needed, and all control could be from the ground, done through a wireless uplink with the space station. The company would not have to change its operations visibly to capture the benefits of microgravity. Since the entire infrastructure would be very mass efficient, costs to execute this would be under $500 million per year. Following posts will further outline the costs of maintaining, supplying, and benefits this infrastructure.