What does MOA mean?
A drug’s mechanism of action (MOA, for short) explains how and why a drug produces its intended effect. As an example, the human body produces prostaglandins that cause inflammation, fever, and pain, among other effects. Two of the enzymes that help produce prostaglandins are COX-1 and COX-2. Ibuprofen is a commonly used, over-the-counter drug that blocks COX-1 and COX-2, which is why ibuprofen reduces inflammation, fever, and pain.
Why does a drug’s MOA matter?
MOA guides further testing of the drug in clinical trials. Knowing how ibuprofen works, an investigator might test it for management of COX-related inflammatory diseases. However, since ibuprofen is not known to impact metabolic pathways, it might not be a good candidate to treat type 2 diabetes.
It predicts a drug’s side effects. COX-2 plays a role in producing prostaglandins that cause inflammation and pain. On the other hand, COX-1 produces prostaglandins that protect the stomach lining. Ibuprofen just happens block COX-1 in addition to COX-2. Because COX-1 gets blocked, repeated use of ibuprofen can reduce the stomach’s mucus production and cause gastric side effects. Knowing this, physicians can appropriately counsel patients on ibuprofen use and closely monitor them for gastric adverse effects, as needed.
MOA can predict behavior of other drugs in the same class. Naproxen is another drug that blocks COX-1 and COX-2, in the same class as ibuprofen. Knowing what we now know about ibuprofen, we can reasonably predict that taking naproxen might help patients with inflammation, fever, and pain with the concomitant risk of heavy use causing gastric side effects.
Revising MOA can result in better drugs. Since blocking COX-2 usefully addresses symptoms and blocking COX-1 appears to cause gastric issues, it would be great to have a drug that only blocks COX-2 since this would do all the useful things ibuprofen does with fewer adverse effects. This logic led to the development of celecoxib: cele short for selective, cox for the COX enzymes, and ib short for inhibitor. Celecoxib selectively inhibits COX-2, causing fewer gastrointestinal side effects than ibuprofen and naproxen while still reducing inflammation, fever, and pain.
These four points provide a sufficient rationale for you to pay attention to it and learn about it.
Why do investors need to know and understand a drug’s MOA?
Determine the degree of differentiation a drug might provide, particularly in the competitive environment at time of launch. As an example, I would be less excited today about the launch of a PD-1 inhibitor in melanoma designed similarly to Keytruda and Opdivo. Since these two blockbusters are already entrenched in the melanoma market, a new PD-1 inhibitor that is expected to be undifferentiated from them would be unlikely to gain significant market share.
Estimate the probability of success. The disadvantage from being late to launch within a drug class could be counterbalanced by the increased likelihood of success. Ojjaara’s clinical development in primary myelofibrosis had a higher likelihood of clinical success since Jakafi, another JAK inhibitor, already demonstrated efficacy.
Assess the potential for indication expansion. Sildenafil, a PDE-5 inhibitor, helps patients with erectile dysfunction and pulmonary hypertension. If you were analyzing tadalafil when it was in clinical trials for a single indication, knowing about the two indications in which sildenafil works would show you that tadalafil might be expanded to at least two indications as well. This could allow you to identify additional revenue opportunities that other retail investors might miss.
These three points provide a sufficient rationale for you to know it for drugs in which you are considering an investment.
A watch-out for investors
MOA is a complex biological topic. For instance, although selective COX-2 inhibition helps with gastrointestinal side effects, it might be associated with worse cardiac effects. Although worse cardiac effects have not been observed with celecoxib, another selective COX-2 inhibitor named rofecoxib has been withdrawn due to this. Keep in mind that inferences in biology often lead to unexpected results when moving a drug from the lab to the clinic.