HIV  is big business. The market for HIV drugs is currently $14 billion, and in the U.S., there is an average lifetime cost of $600,000 per patient for antiretroviral drugs. But while antiretrovirals generally succeed at suppressing HIV and preventing the virus from replicating, they have some major downsides: cost, toxic side effects, and the fact that patients have to remain on them for a lifetime. And with 25 million out of the 33 million people currently infected going without any treatment at all (mostly because of lack of access), there clearly need to be better options.
Koronis Pharmaceuticals , a Seattle-based biotech company, has a potential solution to the HIV epidemic with KP-1461, a new kind of drug that essentially mutates HIV into oblivion. If it works, patients could eventually get off the drug altogether and remain HIV-free.
Traditional HIV drugs attempt to keep the virus in check by preventing it from replicating. But Koronis's KP-1461 uses a new drug mechanism--dubbed Viral Decay AccelerationT--to insert itself into the viral genome, increasing the frequency of mutations, until eventually the virus population collapses. "If you think of HIV as a house made of two by fours, and the genetic backbone of the virus as the foundation of that house, [the drug mechanism] replaces the two by fours with toothpicks, and eventually the house comes crashing down," says Dr. Mark G. Fromhold, VP of Manufacturing and Business Development at Koronis.
So far, Koronis researchers have only been able to use this method to kill HIV in the lab; decimating HIV in the human body will be much harder. But there is hope. In the company's recent Phase 2 clinical trial, patients experienced an increase in the mutation frequency of the virus (the 124-day trial was too short to see any statistically significant drops in viral load , however). And all of Koronis's clinical trials thus far have consisted of monotherapy--patients only take KP-1461 without any other drug--even though the company believes that KP-1461 may work better in combination with currently used antiretrovirals.
In other words, KP-1461 might be successful in eradicating HIV in humans, but no one is really sure yet. If it does work, it won't be a cure in the traditional sense. Patients would have to take the drug for a long time as the virus slowly mutated itself to death.
The next Phase 2 clinical trial will consist of combination therapy. Koronis will also use the trial to find out how long the drug must be used before patients' HIV is completely eradicated. The company has yet to raise money from business partners to conduct the study, which will cost  at least $15 million. So far, Koronis has raised $43 million.
But as the tests continue, Koronis may run into problems forming partnerships with major pharmaceutical companies that are happy with the current state of the HIV drug market. "The business model is predicated on the chronic application of drugs that have very high margins," says Koronis CEO Don Elmer. "What we can say clearly is that there is not a sense of urgency. Collectively [the big pharmaceutical companies] are quite happy to just to let things kind of evolve on their own, and they're not particularly interested in figuring out how to change the overall standard of care." Despite this, Koronis has had ongoing interactions with six of the seven largest pharmaceutical companies for the better part of the last decade.
If KP-1461 does eventually make it to market, it has the potential to "destabilize the worldwide market for antiretrovirals," says Elmer. The drug could more easily be used in rural areas where antiretrovirals aren't easy to come by--in studies, KP-141 has been shown to be "more forgiving" with missed doses than traditional drugs, according to Elmer. And since the drug only needs to be taken for a limited amount of time (the exact amount of time hasn't been determined), it's much more economical than the antiretrovirals that patients must stay on for a lifetime.
There are certainly a lot of "ifs" involved, but it's hard not to root for a drug that could transform the HIV treatment landscape.
[Image: Koronis Pharmaceuticals]