Treatment News

HIV/AIDS Trailblazers Commemorate the
15th Anniversary of AZT, the First AIDS Drug

Future Expected to Bring Continued HIV/AIDS Treatment, Prevention Advances

RESEARCH TRIANGLE PARK, NC, March 19, 2002 - Physicians, patients and scientists who've been involved from the beginning today commemorated the 15-year anniversary of the FDA's approval of the first AIDS drug - AZT (Retrovir®/zidovudine), manufactured by GlaxoSmithKline - and reflected on treatment advances and the evolution of a drug that emerged in a firestorm of emotional turmoil and political activism.

AZT was approved by the FDA March 19, 1987, six months after the Phase II clinical trial was halted early on the recommendation of a National Institute of Allergy and Infectious Diseases' independent data safety and monitoring board. Early data showed a significant reduction in deaths among patients who were taking AZT, compared to those who had received a placebo.

"The first patients involved in these trials were real heroes," said Paul Volberding, M.D., an investigator in the AZT trials that led to the 1987 FDA approval, and currently professor of medicine, University of California San Francisco, and chief of medical services, San Francisco VA Hospital. "Fifteen years ago, AIDS was seen as an inevitable death sentence. Today, we expect this to be a chronic disease."

The early years of AZT and AIDS were challenging as researchers struggled to understand the virus, how it was being spread, how to detect it and how to intervene. They also had much to learn about AZT. At the initially approved dose of AZT, side effects for many were significant. Subsequent studies indicated that the drug was just as effective at lower doses which were more tolerable for patients. By 1995, several new medications were approved and being used in combination with AZT, further improving patient outcomes. "We're living in a dramatically different world today," said AIDS treatment activist Peter Staley.

Staley was diagnosed with AIDS Related Complex in 1985 before any medications were approved to treat the disease. He was a founding member of the activist group ACT Up New York, and currently is the editor of AIDSmeds.com. "I lived the 1980s and '90s thinking I had no future. Today, I'm investing in retirement funds," said Staley.

"AZT was a critical first step - it offered hope to patients for the first time, it spurred HIV drug development, and the world began to see AIDS as a treatable disease," said Douglas J. Manion, M.D., Vice President of HIV Clinical Development and Medical Affairs at GlaxoSmithKline. "Today, AZT is still one of the most prescribed AIDS medications and the backbone of the most common therapeutic regimens."

The March 1996 introduction of a new class of drugs called protease inhibitors (PIs) was a major turning point. Triple combination therapy with AZT, another drug of its class, and a PI was the first example of a potent therapy termed HAART (highly active antiretroviral therapy), often referred to as the "AIDS cocktail."

"I remember the first time I had a patient who was feeling so well with his combination therapy he went back to work," said Margaret Fischl, M.D., professor of medicine and director of the AIDS clinical research unit, University of Miami School of Medicine. Dr. Fischl also was an original AZT investigator and co-author of the report on the study that led to the drug's approval by the FDA. "The patient's insurance company called me and was talking very quietly on the phone, so I asked, `Why are you whispering?' They said, `People with AIDS don't go back to work.' I said, `That was yesterday. This is today.'"

Other milestones that have marked the history of AZT include:

• In October 1986, Burroughs Wellcome (now GlaxoSmithKline), the NIH and the FDA established a model Treatment IND (investigational new drug) program as a means of providing high-risk patients wider access to AZT prior to FDA approval. "Early" or "expanded access" programs based on that model are still used today.
• In May 1990, AZT was approved by the FDA for pediatric use, in children ages 3 months to 12 years.
• In August 1994, AZT was approved for use in the prevention of perinatal transmission in pregnant HIV+ women and newborns. "Studies indicated that AZT reduced the estimated rate of transmission by about two-thirds," said Marty St. Clair, senior virology researcher at GlaxoSmithKline. "For the first time, AZT was saving lives by preventing transmission of the virus." It remains the only drug approved by FDA for this use in the United States.
• On November 17, 1995, the FDA approved Epivir® (lamivudine also known as 3TC®) for use in combination with Retrovir based on clinical studies demonstrating safety and efficacy of the two-drug combination regimen over 6 months in patients with HIV infection. This approval included simultaneous introduction of both an Epivir tablet for adults and an Epivir oral solution product for pediatric patients.
• In September 1997, Combivir® (zidovudine,AZT/ lamivudine,3TC) was approved as the first product to combine two antiretroviral drugs in a single tablet taken twice a day.
• Simplification of AIDS drug regimens continued when, in November 2000, the FDA approved the first combination of three antiretroviral drugs in a single tablet taken twice a day. AZT is also a component of this tablet.

While there has been tremendous progress, there is more that needs to be done.

"Today's therapies don't work for everyone, and they stop working for some over time," Staley said. "We need to continue to find easier to take and more sustainable treatment combinations with fewer side effects."

Researchers at GlaxoSmithKline agree. "Our work is ongoing to further simplify existing regimens and identify new compounds in the fight against HIV/AIDS," Dr. Manion said. "In the last 12 months, GlaxoSmithKline has moved potential compounds into the pipeline, funded basic drug development research projects and initiated our first human trials of a possible HIV vaccine."

In earlier trials, the GSK Biologicals' candidate HIV vaccine protected rhesus monkeys from a highly pathogenic and partially heterologous simian-human immunodeficiency virus (SHIV), a very potent virus similar to HIV. The trial is part of the HIV Vaccine Trials Network (HVTN) created by the National Institute of Allergy and Infectious Diseases to accelerate testing of promising vaccines.

GlaxoSmithKline also continues to study the long-term impact of HIV drugs, including the affect of AZT and other HIV drugs on lipid levels, and groundbreaking work on the role of resistance mutations on the efficacy of HIV drugs. With Shionogi & Co., GSK is studying S-1360, a candidate in a new class of drugs that target integrase, an enzyme that is essential for HIV to replicate. The experimental integrase inhibitor class of drugs offers new hope for patients who develop resistance to existing medications. A trial involving patients who have already been treated with multiple drugs is under way.

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including abacavir, didanosine, lamivudine, stavudine, zalcitabine and zidovudine. Zidovudine has been associated with anemia and neutropenia, especially in patients with advanced disease, and with symptomatic myopathy after prolonged use. The most common side effects of AZT are headache, fatigue, nausea and vomiting.

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Press Release
Elaine Ackert, PCI
Mary Faye Dark
GlaxoSmithKline