The Phase II study was conducted in people with extensive experience using multiple drugs in all classes of antiretroviral therapy. Since tipranavir may be able to suppress multiple-PI resistant and wild type virus with about equal efficacy, it represents an urgently needed therapy for people who've run out of treatment options. Even though primary resistance to tipranavir itself seems to be slow to develop, people who still have an array of treatment choices probably won't choose tipranavir. Besides being a twice-a-day product, ritonavir boosted tipranavir is likely to raise blood lipid levels and cause drug interactions and tolerability problems. Unfortunately, these are factors that will also limit its use among some people who will desperately need it.
Having settled on a dose, Boehringer is now set to start up a pair of large Phase III trials. One study (RESIST 1) will be a 24-week trial in sites throughout North and South America, and Australia. A 16-week trial (RESIST 2) will be conducted exclusively in Europe. The time to approval of tipranavir will depend on how quickly the Phase III studies are enrolled, how much time the company needs to pull its data together for the FDA, and how long the FDA needs to review the application. Mid 2004 would be an optimistic guess.
As the Phase III trials get going, and with the approval of T-20 (Fuzeon) expected in March, it becomes urgent to finalize the details of a tipranavir expanded access program for people with no other treatment options. We know that T-20 has the best shot at working when it is accompanied by at least one other drug active against an individual's viral strain, and for many, tipranavir is the best candidate on the horizon. With access to T-20, tipranavir and atazanavir opening up in the next six months, things might start looking brighter for the growing number of people who critically need an effective third, fourth or fifth-line regimen.