Development of T-1249 put on hold
Simon Collins, HIV i-Base
On 5 January 2004, Roche and Trimeris, the companies that are jointly responsible for developing the fusion inhibitor T-20 (enfuvirtide, Fuzeon) announced that they have put on hold the development programme of the pipeline compound T-1249. 
T-1249 is a second fusion inhibitor in development, and in early studies had shown the potential for greater potency, once-daily rather than twice-daily dosing and activity over T-20 resistant virus. As with other HIV drugs, resistance to T-20 develops unless it is used in a combination with other active drugs.
Difficulties with producing an acceptable formulation are the main reason given for this decision. Although a large investment in the development of T-20 overcame many similar problems, the company does not believe that a similar investment in current approaches to T-1249 would lead to a drug that had a sufficiently beneficial profile over T-20.
Research will continue into new delivery options for T-1249 and other molecules. However, even if successful, in practice patients should not expect access to a second generation fusion inhibitor from Roche and Trimeris for many years.
Both companies were criticised for including the information about stopping T-1249 – clearly the most important news – within a ‘forward-looking’ statement about a new research agreement. 
The only ongoing study will continue for the 40 or so patients still enrolled, and patients still benefiting from T-1249 will continue to receive the drug even after the study closes, but the decision to suspend the research programme closes the door on T-1249 for new patients. This is particularly disappointing for people who have developed resistance to T-20. Early reports of T-1249 presented at the Retrovirus and ICAAC conferences in 2003, indicated that the compound had clear antiviral activity in T-20-resistant patients, whatever difficulties existed with the formulation. [2, 3]
It also has practical implications for patients who are using or considering using T-20 now. Without the promise of a second-generation drug in the pipeline, it becomes even more important to follow recent guidelines to use T-20 when supported by other active drugs, and many patients should either wait until new drugs are available to use with T-20, or use T-20 earlier in treatment failure, when sensitive drugs are still available.
Both BHIVA UK Guidelines and the London HIV Consortium have produced guidelines to this effect. [4, 5]
Use of T20 has been lower than initially predicted, possibly because it has to be given by twice daily injection, and is significantly more expensive than other treatments. Roche is expanding its community and medical education programmes to address these concerns.
- Following the successful development of Fuzeon Roche and Trimeris sign new research agreement to develop next generation HIV fusion inhibitors”. Joint press release from Roche and Trimeris. January 2004.
- Miralles GD et al. T-1249 demonstrates potent antiviral activity over 10 day dosing in most patients who have failed a regimen containing enfuvirtide (ENF): planned interim analysis of T1249-102, a Phase I/II study. 10th Conference on Retroviruses and OIs, Boston, February 2003. Abstract 14lb.
- Lalezari JP et al. Final analysis of T1249-102: T-1249 retains potent short term antiviral activity in patients who have failed a regimen containing enfuvirtide. 43rd ICAAC Conference, Chicago, September 2003. Abstract H-444.