Roche and Trimeris able to make enough enfuvirtide (T-20) for only 12,000 people this year, 32,000 next year, citing difficulties in the manufacturing process

1 February 2003. Related: Antiretrovirals.

Graham McKerrow, HIV i-Base

Roche and Trimeris have announced plans to produce enough enfuvirtide (formerly T-20), which will be marketed as Fuzeon, by the end of this year to treat between 12,000 and 15,000 people.

The companies had planned to produce enough enfufirtide to treat 25,000 people by the end of the year but have encountered difficulties with the manufacturing process of this complex new drug.

Production will be stepped up to treat 32,000 people by the end of next year and 39,000 by the end of 2005.

Enfuvirtide, the first of a new class of drugs called fusion inhibitors, is currently available to fewer than 3,000 people through an international early access programme. The revised manufacturing targets include holding a half-year safety stock for each patient who initiates therapy with the drug.

Excitement about enfuvirtide centres on its ability to lower the viral loads of people who have HIV that is resistant to other drugs. While other antiretrovirals aim to stop HIV replicating, enfuvirtide is designed to block HIV from fusing with a host cell.

There are fears that it could cost $7,000 to $10,000 per patient per year, which would make it the most expensive anti-HIV drug. Some observers have even suggested it could cost $15,000. A spokesman for the company said: “Roche and Trimeris cannot comment on the price because it has not been announced. However, it can be expected that Fuzeon will be significantly more expensive than the most recently introduced AIDS therapies due to its structural complexity and its highly sophisticated manufacturing process.”

Enfuvirtide is expected to receive its US licence in March. The companies say they now have enough data from the first three months of the commercial manufacturing process to provide an update on the progress to date. The following is the text of their statement.

“Fuzeon is one of the most complex and challenging molecules ever chemically manufactured on a large scale by the pharmaceutical industry. Roche and Trimeris have demonstrated that production of Fuzeon at large scale is possible and the first commercial scale production of Fuzeon drug substance has now been completed.

“Roche’s manufacturing plant in Boulder, Colorado in the United States has been working 24 hours a day, seven days a week to meet the challenges required to manufacture this peptide – a complex molecule which requires more than 100 production steps. Initial commercial scale production yields were lower and cycle times longer than had been projected; however, subsequent improvements have been made so that yields have steadily improved to now consistently meet those derived from pilot plant projections.

“Plans are also in place to further improve production cycle times. A rate-limiting step has been identified in the manufacturing process, and plans have already been put in place to increase the capacity of this step, including the addition of duplicate equipment.

“In 2003: Short-term manufacturing estimates for Fuzeon are based on the current estimated ability to produce around two metric tonnes of Fuzeon in 2003 – equivalent to up to 20,000 treatment packs (one treatment pack equals one month’s supply for one patient) per month by year end. This translates to supply for approximately 12,000 to 15,000 patients on Fuzeon by year end 2003.

“This number of patients is lower than would be calculated based upon the manufacturing output for the year due to the fact that approximately half a year ‘safety supply’ is allocated to every patient to ensure continuity of drug supply. We believe that a half-year safety supply is prudent given our early stage of commercial production and the severity of the illness being treated; however, we plan to evaluate the safety supply requirements as we move forward.

“In 2004: Annual production of Fuzeon is planned to increase to around 3.7 metric tons – equivalent to up to 39,000 treatment packs per month during mid-2004. After setting aside patient safety supplies, this will equate to up to a maximum of 32,000 patients on Fuzeon by year-end 2004.

“These figures are based upon the assumption that individual patient safety supply of approximately half a year is maintained and projected cycle times and yields remain on track. As we continue to gain confidence in the process and fill the distribution pipeline, we will evaluate the amount of safety stock required to maintain a continuity of supply.

“In 2005: It is expected that safety supplies will already be established and the manufacturing capacity can therefore supply up to 39,000 patients, based upon the improvements described.

“Fuzeon is the most clinically advanced in an investigational class of anti-HIV drugs known as fusion inhibitors. Unlike existing anti-HIV drugs that work inside the cell, Fuzeon has a unique mechanism of action that is designed to block HIV before it enters the human immune cell. Consequently, Fuzeon is active against HIV that is resistant to the currently available classes of anti-HIV drugs. Regulatory submissions for Fuzeon were filed in the US and European Union in September for the treatment of HIV-1 infection in combination with other antiretroviral agents. Fuzeon was granted priority review status in the US in October, establishing a target six-month review period. Marketing authorisations have also been submitted in Switzerland, Canada, and Australia.

“Because demand for Fuzeon is expected to exceed supply at launch, Roche and Trimeris will carefully manage allocation of Fuzeon, and are working with HIV physician and patient groups to develop a progressive launch plan. The details of this plan will be announced when Fuzeon is closer to launch.”

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Comment

People with virus resistant to existing drugs will welcome the increased production of envufirtide. A sophisticated manufacturing process is required to produce this complex new drug and it is no great surprise that the companies have encountered unforeseen problems. They are to be congratulated on expanding the manufacturing plant to maintain production levels, even if at a lower rate than had been planned.

There remain serious worries about the cost of enfuvirtide with estimates varying from $7,000 per patient per year to more than twice that figure. Even the lower end would be twice the price of many other antiretrovirals. The companies should announce their price as soon as possible and, in order to avoid any appearance that they are making an undue profit, they should also publish the accounting costs of the drug.