Merck developing implant to prevent and treat HIV long-term: MK-8591

A promising new HIV drug could one day be implanted in the body, upending the current paradigm of daily pills.The medicine, MK-8591, is being developed by US drug giant Merck. That could give Merck an edge in a market expected to top $21 billion by 2026, though it's still early days.Merck has been tight-lipped about the project so far. Business Insider spoke with two top scientists about the drug and implant tech, and with HIV experts and others about how the effort could fare.Visit Business Insider's homepage for more stories.The story of one of the most promising HIV treatments being developed today begins in Japan more than a decade ago. When taking a look at modern HIV medicines, Japanese scientist Hiroshi Ohrui saw certain shortcomings. But he also noticed a way to change and improve them. Medical care for people with HIV has come a long way from the days when there were no treatments at all, and a diagnosis often meant death. Today, at least in the US and other wealthy nations, those with the virus can take daily pills to suppress it, and there are also pills that can help prevent people from getting HIV in the first place.Still, 37 million people around the world have the disease, and an estimated 5,000 more infections occur each day, the latest data shows. Even when people have access to medicine, they sometimes forget to take their pills or miss doses for other reasons. That can render treatments ineffective and also could help the virus become resistant to current medicines.The medicine that Ohrui custom-built could get around that and other downsides of HIV treatments, like the need for large doses of medicines. Patented by the Japanese conglomerate Yamasa, best known for its green- and red-capped bottles of soy sauce, and licensed by US drug giant Merck, it's now the basis for a new medicine, MK-8591. The drug's apparent strength and durability could one day make it possible for those with HIV or at risk to eschew their daily pills for more infrequent doses. Someday, a matchstick-size implant could automatically dispense the treatment in the body, upending a market that's expected to top $21 billion by 2026, according to data from Datamonitor Healthcare.Importantly, it's still early days. The implant is an estimated four to five years away from a review by regulators. And for now, it's just being tested out in implant form to prevent HIV, not treat it. But excitement at Merck and around the industry runs high, though the company hasn't spoken much about the projects thus far. Business Insider got an early inside look. “I've been in the HIV field since the 1980s, back when we had really nothing. And now we have really good treatments, and so we're ready for that next wave of innovation,” said Dr. Michael Robertson, executive director of global clinical development at Merck Research Labs and section head for HIV and Hepatitis C. “Watch this space. A lot is going to be happening.”Read more: The treatment that cured 2 men of HIV may also help with a remarkable array of more than 70 deadly diseasesA potent drug that could upend the current HIV treatment paradigmWhen Cheryl Stoddart, a professor of medicine in residence at UCSF, first tested out the Merck HIV drug in the lab, it was so strong that she still struggles with the best way to describe it.It was many times stronger than Truvada, the sole HIV prevention treatment in the US, which has been a best-selling blockbuster for drugmaker Gilead, Stoddard said. Writing about the molecule in a manuscript, she tried out the descriptor “ultra potent,” but an editor took it out. “I've been testing and developing antiviral drugs now for 30 years or so, and when somebody hands you something that's the most potent thing you've ever tested at that point, you take notice,” Stoddard told Business Insider.Potency means that patients can take a small amount of a drug and still get a treatment effect, an enviable attribute for a medication. That also excited Merck's scientists about MK-8591, as did how long the experimental medicine appeared to stay in the body. MK-8591 is part of a category of drugs frequently used to treat HIV. Its apparent potency can be chalked up to a key difference at the molecular level, or an extra group of atoms that Merck researchers believe helps it work better against HIV. Because it has a different mechanism, MK-8591 could potentially be effective for drug-resistant forms of the virus, too, Merck's Robertson said. As a pill, Merck figures it could be taken as infrequently as once a month. The pill form is currently being tested out in people as a once-a-day treatment with other HIV drugs, in a mid-stage trial.The Merck team also decided to think about ways patients could take their medicine even less frequently.Merck has since 2001 sold tiny, rod-sized birth control implants that women can have inserted in their arms, instead of taking a daily contraceptive pill.Combining the implant technology with MK-8591 seemed like the perfect marriage.Harnessing a spaghetti-like manufacturing processSmall and unobtrusive. Those are two crucial facets of Merck's $700 million birth-control-implant franchise, which includes an older version called Implanon and a next-generation one named Nexplanon.To make the flexible, rod-like devices, plastic and pregnancy-preventing hormones are molded into long, thin strands, “just like a piece of spaghetti,” explains Stephanie Barrett, a senior principal scientist with Merck. They're then cut into multiple implants.In rats, a miniaturized version of these implants has been used to test out HIV drug MK-8591. Published research shows that the implant released the drug continuously, for as long as a year-and-a-half in some cases. Merck only stopped the study “because the rats were dying of old age,” Barrett said, calling this early pre-clinical research “really promising so far.”In humans, the drug and implant could last six months to a year. That will require human testing to prove it's safe and effective, with safety being especially important, because the device is intended for long-term use. Studies of the implant in humans could be around two years away, one researcher estimated. Morgan Stanley analyst David Risinger told Business Insider that the opportunity was “exciting,” since if MK-8591 works better than other drugs, there should be a lot of demand. Execution will be critical, though, because implants are more complicated to develop than other kinds of products. Price could also be an issue, since “there will be more generic HIV products available by time they launch this implant,” he said. Cheaper alternatives might make health insurers unwilling to pay for a more expensive, branded product. Why HIV implants have been a long-held dreamHIV implants have been something of a long-desired dream for health professionals who treat people with the virus. A daily pill regimen may not sound especially difficult, especially compared with what one expert called the “bad old days” of treatment. Back then, treatments consisted of fistfuls of pills, each one guided by varying rules. Yet it's harder than you would think, medical professionals say, because for a patient that might mean a pill a day for decades. Then there are barriers like cost, other medications to think about, and the still-enduring stigma attached to HIV. “Taking a pill every day is a daily reminder that you have HIV. And that's hard,” said Susan LeLacheur, a physician assistant who has been treating individuals with HIV since 1987. “There is some stigma, some guilt, some fear, which of course there is. Not having that daily reminder is important for people.” Dispensing medications inside the body automatically, with implants, has become a new frontier for many diseases. And it's especially attractive in HIV, where forgetting to take your pills can have serious health consequences.Existing HIV treatments are a combination of drugs that block spots in the body vulnerable to the virus getting in and spreading. Without that barrier, the disease can morph, making existing medications ineffective. Replacing once-a-day treatment entirely is still a long way off. Merck is starting in prevention, since it'll need to pair MK-8591 with other, similarly powerful drugs for an implantable treatment. Other corners of the healthcare world are also testing out HIV implants, including academic and nonprofit groups working with an existing HIV drug from drugmaker Gilead. Developers are also working towards more streamlined HIV regimens, with once-a-month shots in development, too.In the implant space, there's “nothing else I'm aware of” that's as far along as Merck's project, says Merck collaborator Dr. Charles Flexner, a professor at Johns Hopkins University. Flexner is also involved with a program called LEAP funded by the US's National Institutes of Health to encourage development in this area. Space constraints could also dog other efforts, Merck's Robertson said. There's only so much space in the body for an implant, and MK-8591 could allow for a 100-fold smaller dose, and thus a smaller implant, than the Gilead drug others are working with, he said. Gilead didn't respond to a request for comment.Merck's decades of experience making implants should also help it, Robertson said, noting that the company is also trying the drug out as a pill taken by mouth. “What we really want to see is give patients options. People like options,” Robertson said. “This molecule forms a cornerstone for a number of different ways of approaching this.”