History

1996
Test Results Presented; FDA Approves CRIXIVAN

Full steam ahead.

Starting in April 1995, Phase III testing of CRIXIVAN at a stronger dose of 800 mg every eight hours began. By the time Phase III studies concluded, some 4,000 patients in 11 countries took CRIXIVAN. Merck, physicians treating HIV, and the community all waited anxiously for the results.

In late January 1996, Merck’s Emilio Emini presented some of the initial data from Phase III studies at the Third Conference on Retroviruses and Opportunistic Infections. In what would soon be considered a landmark trial, Protocol 035, CRIXIVAN used alone caused the viral levels to drop to undetectable levels in 44 percent (4 of 9) of the patients after 6 months. However, when used in combination with other drugs known as reverse transcriptase inhibitors, the results were markedly better. The most dramatic effect was shown by patients who had received triple-combination therapy — CRIXIVAN combined with AZT and 3TC. In 6 of 7 patients receiving triple-combination therapy, the virus had been knocked down to undetectable levels (less than 500 copies per milliliter.) This, the first time a drug was shown to knock the level of virus to undetectable, was the most promising data that had been presented so far in the AIDS epidemic. But still, there was caution.

More research was clearly needed to determine the best course of action for the future. Questions remained about long-term effectiveness. Would resistance develop? If so, would virus resistant to one protease cocktail be wiped out by a different combination? Would the virus ever be completely eradicated from the stubborn lymph system, brain, and male testes? Only long-term study would be able to determine the answers. But for patients, and doctors, and researchers, and a public that had suffered through more than a decade of darkness, the FDA's clearance of CRIXIVAN on March 14, 1996 — a record 42 days after Merck had filed — was a bright day at last.