The Agonist/Antagonist Duel for Enhanced Pharmaceuticals
This is the first posting from Scott Alexander. For more information about Scott, click the Author link on this page.
One of the persistent challenges of the Pharmaceutical industry has been maintaining the safety and efficacy of drug products in patients over time. In other words, when a patient starts taking the drug, the patient is able to take a lower, safer dose of the product in order to treat the symptoms. However, over time, the patient becomes desensitized or builds tolerance to the drug such that he/she must take higher, less safe doses of the product in order get the desired effect. Eventually, the dosing may reach dangerous levels causing serious, or even fatal, side effects. The crux of the problem is that the pharmaceutical industry does not really have a handle on how target drug-receptors are activated or de-activated in the body in order to achieve the desired result. As a result, desensitization is viewed as an unavoidable side effect.
Last week, I attended the NYC Bio Meetup. One of the presenters was Richard G. Lanzara, President of Enhanced Pharmaceuticals (EP). EP is attempting to combat the problem described above by modulating targeted drug-receptor effects to create new drug combinations which are safer and more effective. EP’s methodology combines an agonist, which triggers a response from the receptor, with an antagonist, which produces no response from the receptor and can block the action of the agonist, in a calculated formulation in order to optimize the drug’s efficacy while curtailing desensitization. EP has shown promising research for improving products used to treat heart failure and asthma. Additionally, EP believes that drugs used to treat Parkinson’s disease, memory loss and other diseases can be enhanced to reduce patient tolerance.
EP does not yet have a website, but the technology was transferred from Bio Balance, and one can obtain more information about their philosophy and technology on the Bio Balance website. EP’s goal is to license the technology to pharmaceutical and biotech companies so that these companies can develop safer, more effective new products and enhance (and potentially extend the patent life of) their existing product lines.
In my limited research (within the first 10 pages of some Google searches), I did not find any competitors for EP nor did I find anyone refuting the ideas and technology put forth by EP/Bio Balance. However, it may be safe to assume that pharmaceutical companies, small and large, have put significant resources toward developing similar/competing technology. On the other hand, this type of technology brings the ethics vs. profit question into light for Big Pharma. While companies have an ethical duty to put forth the safest and most effective products, they may not be able to sell as much of their product if they do. If they are able to create a product that does what it is supposed to do for as long as the patient needs it without a build up of any kind of tolerance, then the patient will never need to increase dosage (such as taking two pills instead of one) and there will be less of a need for more costly variations/extensions of the same product (e.g. extra-strength” variations). Do pharmaceutical companies really want this technology? EP is betting that they do.
EP hopes to start Phase 1 clinical trials of their technology in the near future. Ideally, the clinical trial process will prove that the technology works and provide answers to some of the following questions:
- Over long periods of time, do the combination products retain their efficacy or does desensitization eventually occur? This question may or may not be answered in clinical trials depending on the amount of time it takes to build up tolerance.
- Will the formula work the same for everyone? Different people build up tolerance at different rates. A drug’s efficacy varies from person to person. Will EP’s formula work the same for everyone or will the ratio of agonist-to-antagonist need to change from person to person?
- What new side effects will appear with the agonist/antagonist combination products? While the adverse affects for agonist alone and antagonist alone may be well known, unexpected events may occur when taken together.
EP’s methodology is certainly something to watch in the coming years. If EP can demonstrate that their technology really works and drug companies buy into it, then consumers can look forward to drug products that get the job done safely every time.
Thank you for your thoughtful blog about my recent presentation of Enhanced Pharmaceuticals at the July 2008 NYC Bio Meetup. As you correctly pointed out Enhanced Pharmaceuticals, has discovered that combining an agonist with the proper amount of an antagonist modulates the targeted receptor response and appears to be a quite general phenomenon applicable to many G Protein-Coupled Receptors (GPCRs). Although it was previously reported for the opioid and nicotinic receptors, no other research group has characterized and optimized their drug combinations using predictive biophysical methods such as ours.
There are at least three companies including Enhanced Pharmaceuticals (Inverseon and Pain Therapeutics (PTIE) being the other two) that were formed around similar empirical findings that agonist/antagonist combinations are better than the agonist alone, but general pharmacological science has been rather slow to follow up on these experimental studies. Perhaps because it is an unexpected result that differs from most pharmacological theories and clinical intuition, it hasn’t caught on in the last 16 years since the filing of my first patent on September 30, 1992. This puzzles me, because these findings represent a paradigm shift in the field toward discovering and making safer and more effective drugs.
With regard to your comments about the ethical dilemma faced by big pharma selling less pills if they are more effective, I don’t believe that to be the case.
Instead, I see big pharma as looking in all the wrong places to extend their patent franchises while ignoring or remaining unaware of technologies such as ours to improve their drugs.
As you mentioned in your question concerning such combinations, there remains more experimental work to do, but I can tell you that from our initial studies it appears that these combinations work well in animals that desensitize differently and that they appear to work after desensitizing a targeted receptor system such as the Guinea-pig trachea (an accepted experimental system for asthma studies). In our animal studies, there were also less cardiac arrhythmias with our drug combinations than with the agonist (activating) drugs alone. These studies are promising, but need further research. Because our work holds such promise for better asthma, heart failure and Parkinson drugs, we continue to hope that investors will see our potential and rise to the opportunities.
Thank you again for your thoughtful and well written analysis!