DMP 266 Now Available
DuPont Merck's potent new non-nucleoside reverse transcriptase inhibitor DMP 266, now called Sustiva or efavirenz, will be made available in October through a limited expanded access program. To be eligible for the program, individuals must have had a CD4 count of less than 50 in the last three months and be "failing therapy or intolerant to their current treatment regimen." (Failing is defined as suboptimal viral suppression, rebound in viral load, declining CD4 count or clinical deterioration.) Sustiva is a non-nucleoside reverse transcriptase inhibitor that has distinguished itself from others in its class by the comparative difficulty HIV has in evolving resistance to it. Whereas delavirdine and nevirapine, the two NNRTIs now on the market, are defeated by a single HIV mutation, Sustiva obligates HIV to mutate at least twice before significant resistance occurs. Still, resistance would not take so long to develop if Sustiva were the only active drug in a patient's combination therapy. For this reason, DuPont Merck is requiring that persons in the expanded access program start Sustiva with at least one other commercial or experimental anti-HIV compound to which that patient has not been exposed. (The hope is that this second agent will also be active against the patient's HIV, resulting in greater viral suppression and the need for more mutations before therapy again fails.) Persons interested in the program may call 800/998-6854 for more information.
Data released in September further confirms Sustiva's activity: After 48 weeks on Sustiva in combination with only the protease inhibitor indinavir, 59 volunteers had a sustained average viral load drop of 2.38 log (99.6%), with 88% of them below the viral load test's limit of quantification (400 copies/ml). An average CD4 count rise of 240 also was recorded. The cohort on the alternative treatment arm in this trial did not do quite as well (and the difference was statistically significant). This group started on indinavir alone for 12 weeks, subsequently adding Sustiva and d4T. At 48 weeks, its mean viral load reduction was only 1.89 log (98.7%), with 68% below the limit of detection. CD4s rose by 150 on average. Baseline viral loads were slightly over 100,000 (5 logs) for both groups.
At the time this trial commenced, critics were concerned about the advisability and ethics of starting volunteers on protease inhibitor monotherapy because of the rapidity with which drug resistance develops with such therapy. The results of those starting on indinavir alone did turn out to be inferior, but not dramatically so.
DuPont Merck expects to file with the FDA for marketing approval in March 1998. This winter, a larger supply of Sustiva will be available, and the company plans to make the expanded access program somewhat less restrictive. (The company says that there is enough drug right now for 2,000 people on expanded access.) People who do not qualify for expanded access can enroll in the phase II/III trials DuPont Merck is conducting. One 750-person trial is testing durability of response in people taking either Sustiva plus indinavir, Sustiva plus AZT/3TC, or AZT/3TC/indinavir without Sustiva. A second trial for 300 persons is testing Sustiva plus each individual's choice of nucleoside analogs versus Sustiva plus indinavir plus a choice of nucleoside analogs. Both trials require volunteers to have no prior history with protease inhibitors. The two trials are about half-full, and DuPont Merck is concerned that recruitment is proceeding slowly. For information about these or other trials, call 800/870-8899.
This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.