By Mary Welch
Gilead Sciences Inc. reported statistically significant preliminary data from two studies showing that daily doses of 60 milligrams of Preveon (adefovir dipivoxil) for the treatment of HIV was as effective as 120 milligrams, but with fewer side effects.
Earlier this week, Foster City, Calif.-based Gilead, said it was acquiring NeXstar Pharmaceuticals Inc., of Boulder, Colo., in a $550 million stock deal. (See BioWorld Today, March 2, 1999, p. 1.)
Gilead plans to file a new drug application (NDA) for the accelerated approval of Preveon for the treatment of HIV-infected patients with clinical, immunologic and/or virologic progression despite prior reverse transcriptase inhibitor therapy. With FDA fast-track designation, Preveon may be on the market by the end of the year.
¿We believe it is a positive report,¿ said Albert Rauch, senior vice president of Everen Securities Inc., of Chicago. ¿We always believed Preveon would be useful as salvage therapy,¿ but now it potentially could be used before salvage therapy. We still need to know more about the data. It has a nice resistance profile, which is going to become increasingly important to HIV patients.¿
Sales Potential Tops $550M, Analyst Says
In addition to the ongoing Phase III studies, the company will continue to investigate the drug¿s efficacy at the 60-milligram dose.
Rauch believes Preveon has a potential of more than $550 million worldwide.
So far, more than 8,500 patients have received the drug, including more than 7,000 in the expanded-access program, at either of the two dosing levels.
The data come from two trials. Study 420 was a four-week, randomized, double-blind, placebo-controlled trial conducted at four U.S. centers with 47 patients. The primary objective was to determine the anti-HIV activity of Preveon 60-milligram monotherapy compared to placebo over four weeks in treatment-naove patients.
Results indicated that the Preveon monotherapy produced statistically significant anti-HIV activity, compared to the placebo. In fact, the anti-HIV activity was similar to the Preveon 120-milligram monotherapy in previous studies.
The second trial, Study 417, involved 214 patients in 22 centers. The double-blind, dose-comparison trial enrolled patients who had received extensive prior treatment with nucleoside reverse transcriptase inhibitors, but not protease inhibitors. Patients were randomly given Preveon at 60 milligrams or 120 milligrams, along with a combination of either nelfinavir and saquinavir, or of a nucleoside reverse transcriptase inhibitor (AXT, 3TC, or d4T), plus nelfinavir or saquinavir.
Interim data at 20 weeks showed that the triple-drug regimens containing Preveon at 60 milligrams were as effective as those regimens with 120 milligrams.
¿Patients in our expanded access program who were randomized to the 120-milligram dose will now be switched to the 60-milligram dose,¿ said Sheryl Meredith, spokeswoman for Gilead.
The studies showed reduced incidence of nephrotoxicity in patients taking 60 milligrams versus those taking 120 milligrams. Nephrotoxicity involves changes in serum creatinine and phosphate, and may bring on kidney-related conditions.
During the testing, the most common side effects were gastrointestinal effects, including nausea and loss of appetite. All patients were given Preveon with L-carnitine, a nutritional supplement.
While the company remains on track for its NDA filing, it plans to begin Phase IV studies to confirm the long-term efficacy and safety of Preveon at 60 milligrams.
¿It will be a well-powered trial,¿ Meredith said.
John Sonnier, vice president of Vector Securities International Inc., of Chicago, wrote in a research paper that the news is even better than expected. ¿As [Wall Street] has been focused on Preveon¿s nephrotoxicty at 120 milligrams at 24 weeks, we believe this data is highly significant and provides additional validation of Preveon¿s potential in the treatment of HIV,¿ Sonnier wrote.
Noting that those in the expanded-access program will now be switched to 60 milligram doses, he estimated those patients alone could ¿represent a revenue base of approximately $20 million, if the product were commercially available.¿
Meredith declined to speculate on sales figures for Preveon, citing the quiet period required by the Securities and Exchange Commission due to the merger.
Adefovir dipivoxil this month is starting Phase III for the treatment of Hepatitis B. The two-year study will yield data within a year. A marketing name for adefovir dipivoxil for this indication has not yet been determined. Gilead will release additional data later this month at the 12th International Conference on Antiviral Research, in Jerusalem.
Gilead Sciences¿ stock (NASDAQ:GILD) closed Wednesday at $41.937, up $1.562. n