Motif Bio Plc (LON:MTFB) Chief Executive Officer Dr. Graham Lumsden caught up with DirectorsTalk for an exclusive interview to discuss the fixed 80mg dose for the Iclaprim Phase III clinical trials
Q1: Your latest RNS stated that the Iclaprim Phase III clinical trials will now be a fixed dose of 80mg for all patients expect those with a moderate hepatic impairment. Why is this fixed dose so important?
A1: I think the fixed dose of 80mg that the FDA has agreed to is important for a number of reasons. First and foremost, when we met with the FDA back in April face to face they actually recommended that Motif use a fixed dose of Iclaprim in the Phase III clinical trials. The reason for that is that the previous dose that had been used, a weight based dose where you basically measure the weight of each patient and then calculate the dose of the Iclaprim dependent on the weight of each patient, was probably not the ideal dose for patients in that it’ probably ended up under-dosing some low body weight and low body mass index patients meaning that there was no enough antibiotic to kill the bacteria causing the disease. So what the fixed dose does, having been recommended by the FDA and now the FDA’s agreed with our calculations of why 80mg is the correct dose, is it gives us an opportunity to optimise the dose in terms of efficacy, so how well Iclaprim will work at killing bacteria with these nasty hospital infections, and at the same time minimising any off-target side effects that might be seen in the clinical trials. So I think this 80mg fixed dose that the FDA has agreed to is really good for patients because it’s the best dose for ensuring what we called efficacy so the ability of Iclaprim to kill the bacteria, it’s also good for the physicians, doctors and nurses who actually have to administer these antibiotics because most of the other antibiotics in a hospital setting, the physician, doctor or nurse has to measure the body weight of the patient then they have to do a calculation, do some measurements, figure out the dose of the antibiotics and administer accordingly. In the case of Iclaprim, that’s not necessary, it’s the same dose for all patients with that one exception, moderate hepatic impairment, which is a relatively low number of patients that we would expect to see. So it’s easier and more straightforward for the doctors and the nurses in the hospital to use a fixed dose. Lastly, because of that, it’s better for the people that are paying for this, whether its governments in Europe or whether it’s insurance companies in the United States, there’s less cost involved with a fixed dose because you don’t have to do all these body weight measurements and measure the amount of antibiotic so it’s quicker and easier. So I think there’s a number of benefits to this 80mg fixed dose.
Q2: How was the dose determined?
A2: So, we had the luxury of having access to data from 500 patients who have previously been treated with Iclaprim and what that means is we can look at how Iclaprim was distributed inside these patients after it was administered. So we have data showing what happens to the levels of Iclaprim over time in patients who have been administered Iclaprim, looking at the blood levels of Iclaprim, and what we’ve been able to do is two things, we’ve been able to select a fixed dose over an infusion period of 120 minutes which maximises the two, what’s called, pharmacokinetics, pharmacodynamics parameters that are responsible for efficacy so our 80mg dose, dosed over 120 minutes gives Iclaprim the best chance of killing bacteria. The second thing we were able to do, based on this data from 500 patients previously treated with Iclaprim, is make sure that our 80mg fixed dose does not go above something called a Cmax which is the maximum concentration of Iclaprim in the blood stream and by avoiding going above the Cmax, we minimise as I said earlier the off-target side effects that might be seen in some patients. So we’ve been able to select 80mg based on how Iclaprim performs in 500 patients that have previously been treated with Iclaprim and measurements of blood levels which guided us to select 80mg for 120 minutes.
Q3: How will this benefit patients?
A3: Well, I think this is the best way to use Iclaprim in patients because it maximises the chance of Iclaprim being effective with minimising any off-target side effects so I think it’s the right dose and therefore, we expect that it’s going to perform really really well in our Phase III trials and so the patients that are in the trials will get the best possible effect from Iclaprim so we’re actually very excited about FDA agreeing to this fixed dose of 80mg.
