BioWorld International Correspondent

Swedish drug development firm Medivir AB is planning to move its nucleoside reverse transcriptase inhibitor MIV-310 to Phase IIb clinical trials, following the release of encouraging data from a Phase IIa clinical study conducted in 15 patients with multidrug-resistant HIV.

The open-label proof-of-principle study was conducted in patients receiving individualized combination treatments comprising three to five drugs, who were exhibiting treatment failure. Over a four-week period, they received a daily dose of 7.5 mg of MIV-310, in addition to their regular regimen. The drug candidate brought about an overall median reduction in viral plasma load of 92.6 percent. Excluding a subgroup of four patients whose drug regimen included d4T (stavudine), that figure rose to a 98.7 percent reduction in viral load. Speaking during a conference call Friday, Vice President for Pharmaceutical Development Johan Harmenberg said virus was undetectable in close to one-third of those who were not taking d4T, which appears to interact with MIV-310.

"This is an extraordinary result, and I have never seen any other drug doing this, even in naive patients," Harmenberg said. "The real reduction is probably even lower, but we cannot measure it."

The subjects' CD4 cell count also responded favorably to treatment. Both it and viral load returned to baseline levels when the treatment was withdrawn.

To be eligible for enrollment in the study, participants were required to have a minimum of a mutation in two of four designated loci on the HIV gene encoding reverse transcriptase - at positions 41, 67, 210 and 215. In practice, they had between 11 and 24 mutations in the gene.

Huddinge-based Medivir now plans to move MIV-310 into Phase IIb dosage studies either later this year or early next year. The company has yet to decide whether it intends to pursue development with a partner or on a solo basis. "That is something still to be discussed and decided on," CEO Jonas Frick told the conference call audience. "The important thing is we are definitely driving the project full-speed ahead."

"We know there is a lot of interest out there," Chief Financial Officer and Vice President for Investor Relations Rein Piir told BioWorld International. "With these results in hand, along with the patent license estate, it is an interesting project."

MIV-310 has a clinical history that stretches back over a decade. It originally underwent Phase I and II studies in AIDS patients in 1991 and 1992. At this time, the problem of multidrug resistance had not developed and, as it failed to show any superiority over zidovudine (AZT), the project was mothballed. More recently, it had to overcome a patent challenge from London-based GlaxoSmithKline plc. The dispute was settled in Medivir's favor in March. Its U.S. Patent No. 6,358,840, which covers the use of MIV-310 as an antiviral against HIV, does not expire until March 2019. Protection in Europe will last until 2012.

Medivir already has entered one major HIV drug development alliance this year, a pact worth potentially $42 million with Basel, Switzerland-based F. Hoffmann-La Roche Ltd. It concerns its non-nucleoside reverse transcriptase inhibitor MV026048, which is still in preclinical development. (See BioWorld International, April 17, 2002.)

An earlier project to develop another NNRTI, MIV-150, in collaboration with Chiron Corp., of Emeryville, Calif., was halted in recent weeks, Piir said.

The company's share price gained almost 14 percent on the Stockholm Stock Exchange Friday, closing at SEK74.5.