Extrapolating from here, for any company pursuing any form of combination treatment for any disease that can show that the combination lowers the dose required, will probably impress any FDA panel.
But there was another factor that the panel was very impressed by. IDegLira patients exhibited no weight gain, while insulin-only patients did gain weight. In fact, over 52 weeks, patients on insulin alone gained weight, and patients on liraglutide alone, lost weight. It makes sense then that patients on the combination, in fact maintained weight. So not only did the dosages stabilize for the combination, but so did weight. IDegLira, however, was associated with weight gain compared to placebo and weight gain compared to GLP-1 alone.
By the end of Novo Nordisk’s presentation, the company was asked a question regarding what to do about patients who need more insulin than the maximum dose allows. Remember, the combination therapy does preclude simply upping the dose, because that also ups the dose of the other drug, which can be dangerous. The company answered that for those patients, individual components would be necessary.
Now, digressing for a moment to the sales question, would IDegLira cannibalize sales from Novo’s Tresiba and Victoza? To an extent, of course yes. However, as we have seen with the results, doses are stabilized with the combination, slowing down insulin resistance. That means patients can in theory live longer and spend more time on the combination before they exhibit insulin resistance, and if and when resistance kicks in and the maximum combination dose is not enough, they can then go to individual component therapy. Studies were not long enough to determine if and when insulin resistance kicks in on the combination therapy.
On net then, the sales implications are that the combination IDegLira will probably increase sales overall for the company by slowing the rate of insulin resistance, at which point patients will likely be forced to go on separate therapies anyway.
Here we get to an interesting part as it applies to any other company pursuing combination therapy for any drug for any disease. One panelist by the name of Dr. Meisel asked the following question:
AND THEN IF I MAY, A THIRD QUESTION, ARE YOU CONSIDERING THESE TWO AGENTS TO BE ADDITIVE OR SYNERGISTIC?
Additive means that the effect of taking the drugs together is the same as them being taken separately. Synergistic means that the effect of taking the drugs together is stronger than taking them separately. Novo’s Dr. Gough answered as follows:
We’re unable to say whether they have — how they’re working. The important point is that both components are contributing to the reduction in A1c across the dose range. But because our studies were treat-to-target studies, by the very nature of the design of the study, we cannot say how they’re working in terms of an additive effect. We can say there’s no evidence of a synergistic effect.
The significance of this answer is twofold. First, a company presenting to the FDA or an FDA panel should never speculate on something that the data cannot corroborate. Dr. Gough was being extra safe here rather than going out on a limb to state a hypothesis. That could have led to trouble because he could have been accused of making suppositions without evidence. Second, combination therapies do not necessarily have to have a synergistic effect. Additive is enough, again important for any company pursuing combination therapies.
