When testing combination products there are several possibilities, normally one has two or more drugs that have already been approved and then the idea is to mix them so the net effect is therapeutically more positive.
Now, if one has Lero (investigational) and an approved existing antiretroviral therapy (ART) the question for the FDA is: how do I ascertain the safety of the mixture? Two things can happen, Lero is unsafe and/or the combination is unsafe (remember the other ART is deemed already as safe as it has been approved) due to a reaction between the two drugs (it happens).
Below the excerpts from FDA guidance document for combination products (my emphasis):
When a new molecular entity (NME) is a constituent part of a combination product, it is critical to consider what information is necessary to characterize the safety and effectiveness of the NME when used in the combination product. Generally, this begins with a consideration of the NME alone.
For example, certain conventional pharmacology and toxicology studies may be necessary to establish the safety profile of the NME alone (e.g., genotoxicity, mutagenicity, immunotoxicity, and local tolerance) before beginning clinical investigation of the combination product.
For a combination product with a drug or biological product constituent that is already approved, it may be possible to tailor the pre-clinical development program to address safety questions posed by the new route or method of delivery, or the change in indication or population. The goal of these studies would be to evaluate changes that may result in a different extent or distribution of drug constituent exposure. To the extent that the combination product permits local or systemic drug exposure that is greater than that occurring with approved dosing regimens, additional safety studies may also be needed to address the higher doses.
So, if the FDA learns that there are already Mono experiments it follows immediately that they would like to know how safe is Lero alone. The higher the doses the better as normally the more is used of something unsafe the more likely it will show in AE’s (not true all the time but almost always). 700mg is an obvious choice as there is the possibility that Mono will be approved with this.
Therefore, FDA requested safety and stability data for 700 mg. As I see it, if the data for 700mg is supportive the Mono route will be much more expedite. Hopefully they will tell soon which is the one they want and voila, the BA will be filled promptly.
You all have a great Thanksgiving.
Now, if one has Lero (investigational) and an approved existing antiretroviral therapy (ART) the question for the FDA is: how do I ascertain the safety of the mixture? Two things can happen, Lero is unsafe and/or the combination is unsafe (remember the other ART is deemed already as safe as it has been approved) due to a reaction between the two drugs (it happens).
Below the excerpts from FDA guidance document for combination products (my emphasis):
When a new molecular entity (NME) is a constituent part of a combination product, it is critical to consider what information is necessary to characterize the safety and effectiveness of the NME when used in the combination product. Generally, this begins with a consideration of the NME alone.
For example, certain conventional pharmacology and toxicology studies may be necessary to establish the safety profile of the NME alone (e.g., genotoxicity, mutagenicity, immunotoxicity, and local tolerance) before beginning clinical investigation of the combination product.
For a combination product with a drug or biological product constituent that is already approved, it may be possible to tailor the pre-clinical development program to address safety questions posed by the new route or method of delivery, or the change in indication or population. The goal of these studies would be to evaluate changes that may result in a different extent or distribution of drug constituent exposure. To the extent that the combination product permits local or systemic drug exposure that is greater than that occurring with approved dosing regimens, additional safety studies may also be needed to address the higher doses.
So, if the FDA learns that there are already Mono experiments it follows immediately that they would like to know how safe is Lero alone. The higher the doses the better as normally the more is used of something unsafe the more likely it will show in AE’s (not true all the time but almost always). 700mg is an obvious choice as there is the possibility that Mono will be approved with this.
Therefore, FDA requested safety and stability data for 700 mg. As I see it, if the data for 700mg is supportive the Mono route will be much more expedite. Hopefully they will tell soon which is the one they want and voila, the BA will be filled promptly.
You all have a great Thanksgiving.
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