New "fusion inhibitor" drug offers Aids lifeline

A revolutionary Aids drug that stops the HIV virus from entering cells may offer new hope to thousands of patients resistant to current therapies.

But the medicine's high cost could limit its use and activists staged a noisy protest at the world Aids conference yesterday to demand improved access to the product.

Data released by drug maker Roche Holding AG of Switzerland and US biotech firm Trimeris Inc showed T-20 slashed the amount of virus in the blood of many patients running out of treatment options.

The injectable drug, which could reach the market in the first quarter of 2003, is the first in a novel class of medicines known as "fusion inhibitors" that work in a completely new way to outwit HIV, the virus that causes Aids.

All 16 of the currently approved Aids medicines attack HIV only after it has entered a human cell.

Results of two clinical trials released at the world Aids conference showed twice as many patients achieved a reduction of HIV in their blood to undetectable levels when taking T-20 plus older drugs as those given conventional therapy alone.

"(The data) is remarkable and far better than expected," said Dr Bonaventura Clotet of the Hospital Germans Trias i Pujol in Barcelona, a lead investigator on the trial, noting that the patients involved had serious drug resistance problems.

In the first trial, 37 per cent of those on T-20 had no detectable virus after 24 weeks against 16 per cent in patients taking older drugs only, while the second study showed a success rate of 28 against 14 per cent.

Resistance to Aids medicines, caused by the rapid mutation of HIV, is a growing problem once again after a brief respite following the introduction of triple-drug cocktails.

Those therapies were based on a new type of drug called protease inhibitors (PIs), launched in 1996, that tamed HIV/Aids effectively for the first time for many patients.

Researchers hope the introduction of T-20 will mark a similar step change in drug treatment for patients who find current drugs no longer work.

"The first milestone was the introduction of PIs at the Vancouver (Aids) conference (in 1996). The second milestone in developing antiretroviral therapies is going to be Barcelona, thanks to this new class of drugs," said Clotet.

Roche and Trimeris plan to file for regulatory approval of the product later this year and the US Food and Drug Administration has promised a fast-track review.

The two companies have yet to disclose how much the drug will cost - but it won't be cheap.

David Reddy, head of Roche's HIV franchise, said T-20 was the most complicated drug ever made, with the manufacturing process requiring 106 steps of chemical synthesis. "It is going to be more expensive than the other HIV drugs," he said.

Andrew Pendrill, an industry analyst with ABN AMRO in London, predicted a price of $10-12,000 per patient a year.

Activists occupied Roche's exhibition stand at the Barcelona conference, accusing the firm of delaying T-20 production to avoid giving the drug away free under "early access" programmes, ahead of its official launch. Roche officials denied the charge.

The fact that T-20 is a lengthy protein chain also means it must be given as an under-the-skin injection rather than a pill, since it would be broken down in the gut before reaching the bloodstream.

As a result, most analysts forecast peak annual sales at a relatively modest $300-600 million, according to independent consultancy Evaluate.

"We suspect that T-20's cost and its twice per day injection will limit its market penetration," Morgan Stanley Dean Witter said.

Fusion inhibitors are the most advanced new drug class in development - Roche and Trimeris have a follow-up compound called T-1249 in early Phase I/II tests - but this week's Aids conference will also hear about developments in other approaches to the disease.

Integrase inhibitors, which block HIV's capacity to insert its genes into a cell's normal DNA, may one day offer a different option for patients with drug resistance.