Progress under way on the microbicide front

Promising advances are being made on the microbicide front: U.S. funding appears imminent for microbicide research and development, a new corporate partnership has been struck with an international research group to step up testing of antiviral AIDS gels, and a number of potential candidates are moving through the research pipeline.

Why is progress so important when it comes to microbicide development? With a microbicide in hand, women would have an effective female-controlled form of protection against infection. Even if a candidate were found to be 60% efficacious, it would aid in averting 2.5 million HIV infections across the globe over three years.1

The Senate Appropriations Committee has passed its FY 2005 foreign operations bill to include a $10 million increase for microbicide research and development, resulting in a total of $32 million aimed at global aid for microbicide research. Final action on the bill is expected by Contraceptive Technology Update press time, estimates Mark Mitchnick, MD, director of research and development for the Silver Spring, MD-based International Partnership for Microbicides (IPM), a nonprofit organization established to accelerate the development and accessibility of microbicides. If approved, IPM will receive $2 million of the increased funding.

"IPM spends 60%-70% of its money right now on research and development, and as time goes on, more and more of that money will be spent on clinical trials and access issues," he states.

Partnering for progress

Extra funding will come at a key time in development of potential microbicide products, as IPM has just reached an agreement with London-based GlaxoSmithKline (GSK) to test several of Glaxo’s proprietary AIDS drugs in a topical form.

"GSK has sent us about eight ingredients or compounds; from those, we will decide if more need to be tested," states Mitchnick. "GSK has a huge library, of course, and these are eight representative molecules."

IPM is taking a comprehensive approach to identify a topical anti-HIV microbicide that includes different classes of anti-HIV compounds, including compounds that could disable HIV prior to contacting the cell or prevent it from multiplying once it enters cells. The organization acquired rights earlier this year to a potential microbicide agent from the Tibotec Pharmaceuticals unit of Johnson & Johnson, based in Mechelen, Belgium.2

After more than a decade of research, dozens of candidate microbicides are in the pipeline; 16 already are in clinical testing, with five of those entering late-stage testing in 2004.3 These candidates include four sulfated or sulfonated polymers, all of which inhibit pathogen attachment to target cells4:

  • Carraguard, developed by the New York City-based Population Council. Made of carrageenan derived from seaweed, the potential product entered a large-scale efficacy trial earlier this year at three South African sites.
  • Emmelle, developed by London-based ML Laboratories. A sulfated polysaccharide known as dextrin sulfate, Emmelle is being tested by the London-based Medical Research Council and the Antwerp, Belgium-based Institute for Tropical Medicine.
  • Ushercell, developed by Polydex Pharmaceuticals in Scarborough, Ontario, Canada, and the Program for the Topical Prevention of Conception and Disease in Chicago. Also known as cellulose sulfate, the potential product is being tested by the Global Microbicide Project and the HIV Prevention Trials Network, both based in Arlington, VA, and the Geneva-based World Health Organization.
  • PRO 2000, under development by Indevus Pharmaceuticals of Lexington, MA. A synthetic polymer that binds to the HIV virus, the potential product will be tested by the London-based Microbicide Development Programme in full-scale clinical trials scheduled to begin in 2005 in several African countries.

Another potential microbicide, Savvy, is in two Phase 3 clinical trials in Africa to test its efficacy in the prevention of HIV transmission. Also known as C-31G, Savvy is a surfactant that disrupts the outer surface of pathogens. Savvy is being developed by Huntingdon Valley, PA-based Biosyn, which is set to be acquired by San Francisco-based Cellegy Pharmaceuticals.5

Look for more growth

Another potential microbicide, Amphora, has received Food and Drug Administration (FDA) approval for use as a personal lubricant. Clinically known as Acidform, Amphora is an acid-buffering gel that coats the vaginal wall and cervix to maintain a woman’s natural pH level between 3.8 and 4.2. Originally created by the Program for the Topical Prevention of Conception and Disease, Amphora was licensed to Instead of La Jolla, CA, in 2002, with patent protection granted in March 2004.

The company is evaluating Amphora in tandem with a version of its Instead Softcup as a possible contraceptive method in addition to its research as a potential microbicide, says Ariel Cassady, a company spokeswoman. Contraceptive clinical trials using Amphora and a version of the Instead Softcup are scheduled to begin in Russia in January 2005.

"We are still assessing plans to market Amphora as a stand-alone lubricant," she states. "There is a possibility that it will not be introduced to the U.S. marketplace until we have obtained FDA clearance to market it with our Instead Softcup as a contraceptive device."

References

1. Watts C, Zimmerman C. Violence against women: Global scope and magnitude. Lancet 2002; 359:1,232-1,237.

2. Alliance for Microbicide Development. Glaxo AIDS drugs to be tested in topical form, as microbicide. Alliance Weekly News Digest 2004; 5:3-4.

3. Larkin A. Senate appropriations committee passes FY ’05 foreign aid spending bill and includes $32 million for microbicide development. Press release. Sept. 16, 2004. Accessed at: www.microbicide.org.

4. Van de Wijgert J, Coggins C. Microbicides to prevent heterosexual transmission of HIV: Ten years down the road. BETA 2002; 15:23-28.

5. Cellegy Pharmaceuticals to Acquire Biosyn. Press release. Oct. 8, 2004. Accessed at: www.cellegy.com/investors/press/08oct04.html.