Was KP-1461 found to be not a good drug?

Question

Everything I've been able to find out about the drug (which is a prodrug, I could glean that it becomes KP-1212 inside the cells, in a process involving triphosphorylation) sounds very promising except that latest information is from the year 2011.

https://pubmed.ncbi.nlm.nih.gov/21032953/ says or asks "KP-1461: a novel anti-HIV drug in limbo? "

https://go.drugbank.com/drugs/DB05644 says "Phase 2 trials terminated". I don't know what that means.

Wikipedia says, "KP-161 is an experimental antiviral drug being studied for the treatment of HIV/AIDS.[1] It belongs to the class of nucleoside reverse transcriptase inhibitors.

KP-1461 is a prodrug of the active antiviral agent KP-1212.[2]" and that's all it says.

Given that this drug was being touted in the mainstream media in 2005 as a possible cure for AIDS, e.g. https://www.seattletimes.com/business/biotech-firm-launches-test-of-hiv-drug/, and in 2011 e.g. https://www.fastcompany.com/1774219/new-plan-mutate-hiv-out-existence, I can't understand how it has seemingly been forgotten about.

Also, if it works to eradicate HIV from the human body, it might do the same thing with a coronavirus, as well as with other pesky viruses such as hepatitis c.

https://en.wikipedia.org/wiki/Koronis_Pharmaceuticals describes the company behind KP-1461 in the present tense, and yet a glance at the numerous references shows that they are all from 2011 or earlier.

So my question is: was KP-1461 found to be not a good drug?

Answer 1

From Mullins, J. I., Heath, L., Hughes, J. P., Kicha, J., Styrchak, S., Wong, K. G., ... & Parkins, J. (2011). Mutation of HIV-1 genomes in a clinical population treated with the mutagenic nucleoside KP1461. PloS one, 6(1), e15135., bold added by me:

Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first “mechanism validation” phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered

In other words, they gave the drug to HIV-infected patients, but it didn't reduce their viral loads. In short, it didn't work, or at least didn't work in any clinically meaningful way. Note that this is a paper funded by the company that holds a patent on this drug, so they've got a lot of interest in it working out, and the paper itself is mostly about "how a similar drug might work even though this one didn't".

It seems like the drug did well in vitro, and didn't show any serious safety events in early phase 1 trials, but also didn't show any trend towards efficacy in phase 2 so they stopped trials.

This is pretty typical - most drugs that are tested never make it to clinical use, either because they have side effects that are too serious or because they just don't work. It's normal for these drugs to be touted in media like you are mentioning - a lot of times these are based on press releases by companies that own the drugs, they're trying to attract investors to fund trials (which are very expensive). Academic labs do the same thing for grant funding. I think you're underestimating the work done by words like "possible", "potential", "promising", etc - when you're trying to cure something difficult like HIV/AIDS, there are undoubtedly going to be many promising avenues that fail.

clinicaltrials.gov is a good resource for this sort of thing, you can search by just the name of a drug if you know it. For a company that has IP on a "promising" drug, trials that have been terminated a long time ago without and new trials is a pretty dead giveaway that something went wrong. Finding out exactly what (safety? efficacy?) can be a bit more challenging since there's no mandate that trial results are published openly, but often there will be some paper out there.