March 8, 2006
Tibotec is the first company in the battle against AIDS to have two promising new drugs simultaneously under development (TMC 114, a protease inhibitor, and TMC 125, a non-nucleoside). This is good news for patients who need access to more than one active drug to improve control of their multiple drug resistant HIV. In separate studies, both drugs have shown to help reduce viral replication in treatment-experienced patients. A small pilot study has shown that the combination of the two drugs can suppress the virus to undetectable levels at week 16 in patients who have failed all commercially available drugs. TMC 114 is now available via expanded access and TMC 125 is available through a phase III study. But getting the combination of the two drugs to people in need is still a challenge.
"Patients that have developed HIV drug resistance to all commercially available antiretroviral medications require access to at least two new active drugs to maximize their chances for treatment response and survival," said Nelson Vergel, a salvage patient who founded SalvageTherapies.org and board member of the ATAC. "Commercial access to Tibotec's drug combination will not become available for over a year, and many patients cannot wait that long," added Vergel.
The Drug Development Committee of the AIDS Treatment Activists Coalition (ATAC-DDC) and the European Community Advisory Board (ECAB) met with Tibotec a year ago, where they requested early access to both TMC drugs in combination for those who have run out of treatment options so that these patients would not be exposed to the risk of having only one active agent. Unfortunately, Tibotec did not accept this request and instead decided to open a placebo-controlled study (DUET) that provides a 50 % chance of getting TMC 114 as a sole active agent. While the community welcomes Tibotec's decision to combine both of their drugs in a study, it cautions that the placebo arm will fail to help those HIV patients most in need.
Drug resistance and its impact on HIV treatment are major concerns among AIDS activists. More often antiretroviral medications stop working as a result of drug resistance. In fact, national statistics show that at least 46 percent of people failing HIV medications and 13 percent of newly diagnosed patients have drug resistance. Some estimate the number of people living with multiple drug resistance at 64,000 in the United States, many of who have gone through at least four HIV medication regimens already.
"When patients do not have active agents in their optimized background treatment regimen, adding one new active drug to that OBT is considered to be 'virtual mono-therapy.' As observed in many previous studies, some of the 600 patients randomized to Tibotec's placebo arm will obtain a degree of viral suppression in the short term, but benefits may be short-lived and resistance to TMC 114 can emerge in those with no other active agent in their OBT," summarized Fred Schaich, a long term treatment activist and founder of the International Foundation for Alternative Research in AIDS (IFARA). He added, "This problem will limit the use of TMC 114 in the future as part of a fully suppressive regimen."
The DUET studies are important clinical trials for Tibotec; they need to be completed successfully so that etravirine (TMC 125) can be approved. They are also placebo-controlled studies. This means that half of the group of patients will receive etravirine (TMC 125) and the other half will receive a placebo of TMC 125. Patients in both groups will receive darunavir (TMC 114) and any approved nucleoside reverse transcriptase inhibitor and/or the entry inhibitor Fuzeon.
To get around Tibotec's lack of a formal compassionate program, activists are trying to make people aware of a little known process called Emergency IND (EIND) that doctors can use to get access to an investigational drug, provided that the patient meets the criteria and that the manufacturer agrees to provide the drug. This system should help those with little chance of survival and who have no time to wait for drug approval. Unfortunately, EINDs are time consuming and require approval from the manufacturer, the FDA, and local institutional review board. For more information of this procedure and other options soon to be available, go to www.salvagetherapies.org/announcements.htm.
"With hardly any immune system left and resistance to all approved HIV medications, I have tried desperately to get access to both TMC drugs to help save my life, but my doctor tells me that I have little choice but to join the DUET study and take a 50% chance that I may get better," said Gary Bishop, a patient in dire need in Los Angeles who feels time is running out for him.
"We have received and facilitated Emergency IND requests for our compounds and will continue to do so on an individual patient basis if a physician calls us. But note that patients who are eligible but choose not to participate in the DUET trials would not normally be candidates for an EIND," said Lew Sibert from Tibotec. "Patients should discuss all of their options carefully with their physicians before determining the best course of action."
"It would be a lot easier for patients and doctors if Tibotec did the right thing and agreed to the community's original request to have a formal open label compassionate program as soon as possible. This will remove any obstacles due to EIND's extensive paper work, doctors' time and confusion by providing access to several patients at once instead of on a case-by-case basis," said Nelson Vergel. "It is the most humane and ethical thing to do," he added.
Want to make a difference? Write a letter to Tibotec asking them to accelerate their compassionate program for TMC 125 (they have an expanded acecss program for TMC 114). Their address is:
Dr. Brain Woodfal
1020 Stony Hill Road
Yardley, PA 19067