In the news ... 2006 archive

Progenics Ramps Down Developing
PRO-542 and Switches to PRO-140

September 12, 2006

Progenics Pharmaceuticals has quietly ‘ramped down’ the development of their entry inhibitor PRO-542. The company briefly mentioned this decision in a 2005 press release focusing on their other experimental drug, PRO-140. PRO-542 is a monoclonal antibody entry inhibitor that was designed to block the CD4+ receptor on T cells.

Clinical testing of PRO-542 began in 2001. Studies of the drug apparently ended sometime in 2005 without much fanfare. Instead, the company is now developing a different product, PRO-140—also a monoclonal antibody, but one which is designed to block the CCR5 receptor on T cells.

The company’s brief 2005 press release stated that, “In the HIV therapeutic area, we are concentrating our resources on PRO-140 … and we will ramp down our development efforts on PRO-542, our other HIV product candidate.” The release goes on to say that the company will retain PRO-542 for possible future development.

Since most information resources, including the government’s clinical trials website, still list PRO-542 as being in active development and only a few sites have noted the new trials of PRO-140, Project Inform checked with the manufacturer to get a clearer picture of what their current strategy is and the reasons for it. It appears that the company made the decision to switch to PRO-140 because it appears to be a significantly more potent drug. Laboratory studies show PRO-140 to be 20 times more potent than PRO-542 against wild type HIV.

Additionally, PRO-140 has a much better half life of two weeks vs. three days for PRO-542. This means that half of the PRO-140 from a single dose remains in the body after two weeks, while half the dose of PRO-542 remains for only three days. Three days would be considered a very good half life in most circumstances, but it pales against a drug with a half life of two weeks.

This excellent half life of PRO-140 suggests it may be possible to dose the drug only once a week or even less frequently. This is particularly significant since, like most monoclonal antibodies, it currently requires intravenous infusion. The company says it is also working on developing an oral form of the drug, although this will be a difficult challenge.

PRO-140 is currently undergoing Phase IB testing—in this case a type of “proof of concept” test.

Just how to develop this and other new drugs has become unclear in the last few months. For the past several years, the quickest and easiest way to develop a drug for HIV has been to test it in highly treatment experienced patients who are failing all current therapies. This is called salvage therapy. It was an effective way to see if a new drug really worked because there were few if any other options for the patient.

This strategy has been crippled in the last few months due to the success and availability of Tibotec’s new protease inhibitor Prezista, Merck’s integrase inhibitor MK-0518 (expanded access began 9/11/06), and expanded access for Tibotec’s etravirine. Almost all salvage patients now have new options that are very likely to be helpful, so it will no longer be easy to see the effects of a completely new experimental drug.

HIV drug development needs new strategies. The next issue of PI Perspective—Project Inform’s treatment information newsletter—will contain a more detailed discussion of the future challenges of drug development for heavily treatment experienced people.