Pharmaceutical giant GlaxoSmithKline’s experimental therapy aplaviroc has hit a roadblock as a first treatment for HIV-infected patients after two people in its phase IIb clinical trials suffered serious liver problems.

Contrary to some reports, the London-based company is continuing with the final-stage trial of the drug for patients who have tried other therapies. The final-stage trial began in July, according to a Glaxo spokesperson.

However, some analysts were skeptical. “We believe this most likely is the end of aplaviroc in first-line HIV therapy,” wrote HSBC analysts Stuart Harris and Michael Leuchten on Monday.

Aplaviroc is in competition with several other drugs in development that belong to a group called CCR5 antagonists because they are targeted at a cell membrane protein called CCR5.

Glaxo was already lagging behind Pfizer in starting final-stage trials. The news is likely to put Pfizer’s drug UK-427,857 even further ahead.

Current treatments inhibit the HIV virus’s replication once it is already inside the cell. CCR5 antagonists, however, work by stopping the HIV virus from getting into cells in the first place. This suggests they could work synergistically with existing drugs.

“These characteristics have led commentators to suggest that CCR5 antagonists should ultimately revolutionize anti-HIV drug therapy by replacing twice-daily multi-pill drug regimes with once-daily regimes of a CCR5 antagonist and a protease inhibitor,” said Mr. Harris and Mr. Leuchten.

“This would have the additional benefit of reducing the number of patients who fail therapy due to lower viral mutation rates in using this combination,” they added.

Different HIV Treatment Approaches

Pfizer and GlaxoSmithKline have taken slightly different approaches in developing their CCR5 antagonists. Pfizer has decided to compare two combinations of three different drugs, with UK-427,857 in just one of the combinations.

This “more traditional” approach, according to Mr. Harris and Mr. Leuchten, appears likely to give Pfizer the valuable first approval.

However, other companies developing drugs in the CCR5 antagonist class must be concerned about the findings. Glaxo believes it is too early to say whether this will have an effect on the overall class, though.

“With treatments for anti-retroviral experienced patients, the risk benefit profile becomes a bit different,” said a Glaxo spokesperson. “We can’t comment on Pfizer’s drugs.”

In April, Pfizer withdrew its COX-2 inhibitor, Bextra, because it belongs to the same class of drugs as Merck’s Vioxx (see Pfizer Yanks Bextra off Market).

Shares of Glaxo were up $0.47 to $50.12 in recent trading, while shares of Pfizer were down $0.24 to $25.66.