Merck's Letermovir for CMV Prevention Approved by FDA

Roy F. Chemaly, MD, MPH, infectious disease specialist from the University of Texas MD Anderson Cancer Center in Houston, Texas, discusses the background behind letermovir and what it brings to the table.

Interview Transcript (modified slightly for readability):

"Let me give a bit of background about cytomegalovirus (CMV) [treatment]. For at least 15 years now, we have not had any drug that was safe to use in oral form to prevent this infection in special populations, [such as those who have received] a stem cell transplant or an organ transplant. What we have on the market so far are mainly intravenous (IV) drugs. [We have] some oral drugs, but mainly, they are IV drugs, with some serious adverse effects. (These could be from bone marrow suppression or kidney dysfunction.) This is why, for the past 15 to 20 years, we have had a strategy where we look for CMV, and when it starts replicating, [that is when] we start treatment for a short course with these toxic drugs, in order to try and prevent the long-term effects and the side effects from [the drugs].

Now, with letermovir coming to the market, I think it is going to change the way we approach CMV infection in this patient population. Now we have a drug that can be given orally, and it is safe and effective at preventing CMV. We are [no longer] waiting for the infection to manifest in the blood. We will try to prevent it way before [it occurs] and will keep the patient on this oral drug for the duration of the high-risk period.

I think that we are going to see a paradigm shift in approaching and managing CMV infections. We are going to want to go with prevention, instead of preemptive therapy where you wait for the infection to start, and then you treat it with IV drugs.

I have been involved in the development of this drug since the beginning. We did the phase 2 trial initially in a smaller sample size of patients. Later on, with the phase 3 trial, we had a much bigger sample size. I will tell you, based on the data, [letermovir] is an effective drug. Even after we stopped the study drug and we continued to follow the patients to week 24, we saw an impact on CMV activation, compared to the placebo. Also, what was interesting is that we found that at week 14 and week 24, there was an impact on mortality as well. Fewer patients died while on the letermovir arm versus the placebo arm at week 24.

I would say to my colleagues that this is the first drug in the past 20 years that has been approved for CMV prevention in the stem-cell transplant population and that it is effective and safe to use. When we looked at the safety profile, we did not find any signals to tell us that it can cause any serious events, based on the phase 3 trial and the phase 2 trial. It is safe, well-tolerated, and available in IV form as well. You would probably need this IV formulation early on after a transplant when a patient cannot eat or swallow pills. We use it for 1 or 2 weeks in some of our patients and then you switch to the oral formulation later for up to day 100 or week 14, based on the trial.”