The next new anti-HIV drug to be approved by the Food and Drug Administration (FDA) is likely to be darunavir (previously known as TMC-114 and soon to have the trade name Prezista). This protease inhibitor (PI), developed by Tibotec Therapeutics, is designed to work for people whose virus has developed resistance to any of the currently approved PIs. Tibotec has submitted data from phase II studies to the FDA, which is expected to rule on it in late June 2006.
Based on promising results of earlier studies (called POWER 1 and 2), there is little doubt that the FDA will approve this drug. The drug will initially be approved only for people with PI resistance, like another PI called Aptivus (tipranavir). The manufacturer is expected to quickly complete other studies in people just beginning therapy, thus widening the drug's approval.
Based on its high potency, its strong barrier against development of resistance, and its low level of toxicity seen so far, there seems little doubt that the drug will succeed as first line therapy. This might make it one of the most important drugs in the anti-HIV arsenal. Although completing studies to prove its value in first line therapy will take at least another year, once it's approved for any group of patients, doctors are free to prescribe it for anyone they wish.
It is less clear, though, whether insurance companies and other payers will be as quick to offer reimbursement until these other studies are completed. However, if darunavir offers all the advantages people are hoping for, even payers may see it as a real advance and move quickly to offer reimbursement. The price charged for the drug may play an important role in how supportive payers will be. (For more information, read the article "Drug Pricing -- and What You Can Do About It" in this issue of PI Perspective.)
Another new drug from Tibotec should enter expanded access in late 2006 or early 2007. Etravirine (TMC-125) is an experimental non-nucleoside reverse transcriptase inhibitor (NNRTI). It is designed to work on viruses that are resistant to other NNRTIs, like Sustiva (efavirenz) and Viramune (nevirapine). This is a potentially important development, as all of the current drugs in this class are highly cross-resistant -- meaning that HIV that develops resistance to one is likely to be resistant to the others. Between etravirine and a second and possibly more potent NNRTI in development at Tibotec (TMC-278), the curse of cross resistance may be conquered for this class of drugs.
Tibotec is also responsible for a unique advance in HIV research beginning in the spring 2006. It is the first study that combines two experimental anti-HIV drugs at the same time. The trial, called DUET, will study darunavir + etravirine vs. darunavir alone in people with resistant virus -- with both groups taking optimized background therapy in addition to the experimental therapy. This study is enrolling now, and data should start coming out in 2007. Tibotec deserves recognition for this innovative approach. For years researchers and companies have urged patients with resistant virus always to start two new drugs at the same time, but this is the first time a company has made it possible for those with the most serious resistance problems.
2006 will see two important milestones for an entirely new class of drugs called integrase inhibitors, represented by Merck's MK-0518. Large, pivotal Phase III trials of MK-0518 began enrolling in spring 2006 and the company will open an expanded access program no later than fall 2006. (Expanded access programs provide some people early access to experimental drugs prior to approval.) For a more detailed discussion of MK-0518, read the article "Drug Pipeline Offers Diverse New Therapies and Hope." Early indications are very positive for this class of drugs and for MK-0518 in particular, which is the farthest advanced in development. FDA approval is likely in 2007.
Two other major advancements expected in the near future aren't new drugs, but hopefully better ways to use existing drugs. The first is a needleless injection system for the entry inhibitor (EI) Fuzeon (enfuvirtide, T20). The device, called a Biojector, uses high pressure carbon dioxide to inject the drug under the skin, rather than through a metal needle. The hope is that this new system will result in fewer injection site reactions and be easier to use. There is no firm timetable on this, but it looks possible to make it on to the market by the end of 2006.
The final and some think most impactful, anticipated development is the first one-pill-a-day full anti-HIV drug regimen. This new pill will combine three elements of one of the most highly recommended combinations -- Sustiva (efavirenz), Viread (tenofovir) and Emtriva (emtricitabine, FTC). While another pill on the market, Trizivir, contains three drugs -- Retrovir (AZT, zidovudine), Epivir (3TC, lamivudine) and Ziagen (abacavir) -- it is not considered sufficiently potent to serve as a full treatment regimen. It also requires two daily doses. The new combination is a single pill that is taken just once a day.
This achievement required the cooperation of two companies, Gilead Sciences and Bristol-Myers-Squibb, each of which will sell the drug. This level of cooperation, unprecedented in HIV, is good for patients, good for payers (if it's priced fairly) and good for business. The new three-drug combination has been submitted to the FDA for approval and it should be in drug stores by the end of 2006. Because of its advantages, it's likely to be approved faster than this. Let's hope that this will inspire greater cooperation between other pharmaceutical companies.
Looking a bit further into the future, 2007 may see the approval of another type of EI, called a CCR5 inhibitor. Though some experimental drugs of this type have failed in clinical studies, at least one (from Pfizer) continues to show strong performance and another (from Schering) is being studied in treatment-experienced people.
A closing note of caution: While we have hopes for all of the new drugs and products mentioned above, the full story isn't known yet about any of them. Most of the drugs discussed here are experimental and haven't yet been fully proven to be effective. Even at their best, they will still require lifetime maintenance, which is not a cure for HIV disease. At Project Inform we will continue to work toward the goal of a cure, which must be the real goal of AIDS treatment research. Until then, we welcome all advances in HIV care and treatment.