New drug development process presentation
The IMPACT convention center became a microcosm of the world in the most diverse AIDS meeting to date with people of all colors and ethnicities, including Buddhist monks, African tribal women, Thai sex workers, Euro gay men, American treatment activists, children and everything in between. Asian AIDS activists took the opportunity to focus on their own life or death issues surrounding access to AIDS medications, hence the theme of the conference "Access for All." The pharmaceutical company's sales booths were a pathetic ploy for profit, but marauding activists closed many down.
Some delegates looking for any major scientific news may have been disappointed to say the least. In the whirlwind of community activity and political mobilization, any AIDS medical breakthroughs were lacking.
There was limited drug development progress reported in Bangkok, including information about pipeline AIDS therapies from new drug generations, and strategies to make current treatments more useful in terms of tolerability and effectiveness. Successes in coping with some complications of AIDS were also presented.Most of the progress in terms of new drugs presented was very preliminary, early stage or preclinical - not ready for prime time. Nevertheless, there was some information presented, even though somewhat under-whelming.
New Drug Classes
Two new generations of drugs presented in Bangkok that are early in development are the entry inhibitors and maturation inhibitors. The former drugs prevent HIV from entering the cell; the latter drugs stop a later stage of development of HIV.
Entry inhibitors known as CCR5 antagonists coat the co-receptor on the T-cell in order to block or stop attachment of HIV. Pfizer's UK-427, 857 is furthest along in development. Five poster presentations showed the effect of food on different dosing levels of the drug as well as the effect on a cardiac signal called QT interval that was previously shown to be impacted by co-receptor antagonists. Other early stage developmental studies were presented that have enabled the drug to move into larger studies. The best news is that UK-427, 857 is shown to produce between 10 and 100-fold drop in virus levels after ten days of treatment. This is a similar potent effect of the protease inhibitors. Pfizer is in a race against Schering-Plough's SCH-D, another co-receptor antagonist that is being studied with a Norvir boost. Both drugs are taken orally and are being studied at either once or twice daily dosing regimens. Pfizer is undertaking a Phase II comparative study and will move into large Phase III studies by year's end. There is an inkling of hope that the co-receptor antagonists will work in synergy with other entry inhibitors.
PA-457 is being called a "maturation inhibitor" because it inhibits the final stages of HIV protein processing. Three presentations shown in Bangkok have defined the target for this compound and proved in animals and HIV-negative males that the chemical can be metabolized and is well tolerated at various doses needed to reach appropriate blood levels. It appears that the drug will not cross-react with other anti-HIV drugs. It was also presented that PA-457 has potent anti-HIV activity in immuno-compromised SCID-HU mice, which is a positive development. The drug will most likely be a once daily oral pill. The fact that this is a new class targeting late stage HIV is real progress for those who are resistant to the current drugs and need more treatment options from new classes.
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