For two years after gaining approval of its HIV product Fuzeon, Trimeris Inc. has worked to develop next-generation peptide fusion inhibitors, but now it will branch its HIV research into a whole new area - small molecules.
The Morrisville, N.C.-based company signed a collaboration with ChemBridge Research Laboratories Inc. (CRL) to discover and develop small-molecule entry inhibitors of HIV.
The companies will work to identify compounds against two HIV entry targets, gp41 and gp120. Once they have orally active lead compounds, they will optimize preclinical candidates, which Trimeris will take into clinical development.
"There's no doubt that ChemBridge brings to the table some unique capabilities, supporting our medicinal chemistry," said Steven Skolsky, CEO of Trimeris. "We've been heavily involved in terms of providing a deeper insight and understanding of these targets with the generation of our lead and marketed compound, Fuzeon, and now we're looking to expand that knowledge."
Trimeris will be responsible for worldwide preclinical and clinical development of the candidates, as well as manufacturing, regulatory and commercial activities, and it will pay CRL for exclusive medicinal chemistry efforts. San Diego-based CRL also will be entitled to receive undisclosed milestone payments related to development and commercial achievements, as well as royalties.
Fuzeon - Trimeris' only marketed product - gained FDA approval in March 2003 for HIV infection in treatment-experienced patients. The drug, partnered with Hoffmann-La Roche Inc., of Nutley, N.J., is the first HIV entry inhibitor to reach the market. It had sales of $135 million in 2004, an increase of $100 million from the prior year. The drug could reach sales of $500 million at peak, according to some analyst estimates.
While the product has made Trimeris a well-recognized name in the biotechnology industry, the company has had little else in its clinical portfolio. In January 2004, it halted Phase I development due to formulation issues of a second-generation fusion inhibitor, called T-1249, and it reduced its staff by about 25 percent. The company redirected its resources toward more patient-friendly peptide fusion inhibitors that are appropriate for chronic administration. (See BioWorld Today, Jan. 7, 2004.)
While Fuzeon has been "heralded in scientific and clinical circles," Skolsky said, the drug has fallen short for some patients due to its mode of delivery.
"The fact that it's an injectable drug, that it causes site reactions, has been a focal point of our product development improvement efforts," he told BioWorld Today.
By the end of this year, Trimeris expects to have a clinical candidate that might deliver the drug "in a much less frequent regimen, and not require reconstitution," Skolsky said.
Fuzeon, which is delivered subcutaneously twice daily, received accelerated approval based on 24-week Phase III data of 1,000 patients. When taking Fuzeon, the patients were twice as likely to achieve undetectable plasma levels of HIV compared to patients receiving an individualized regimen alone. The drug received traditional approval in October 2004 based on 48-week data.
Unlike traditional HIV products designed to work inside the cell, Fuzeon works on the cell surface by blocking the virus from entering. It is active against viruses that have developed resistance to other drugs.
"We're pleased with the progress that we've made with Fuzeon," Skolsky said. "There's been solid steady growth of the product, and broader acceptance by physicians and patients."
Trimeris has conducted some post-marketing studies evaluating the use of Fuzeon with different delivery systems, such as the B-2000 needle-free device marketed by Bioject Medical Technologies Inc., of Bedminster, N.J. The company plans to submit its bioequivalence data as part of a supplemental new drug application, shooting for approval of the new delivery method by the end of this year. Approval would allow Trimeris to promote Fuzeon's use with B-2000 and to make label changes.
While it makes improvements to Fuzeon and brings a second-generation peptide into the clinic, Trimeris will continue to work in the area of HIV entry inhibition through its new program with ChemBridge. Skolsky said the research is in the early stages, and he could not yet give a timeline as to when the first small molecule might reach the clinic.
ChemBridge was founded in 2000 as an independent spin-off of San Diego-based ChemBridge Corp. It is privately held.
Founded in 1993, Trimeris went public just four years later in October 1997, raising $33 million. It last raised $108.6 million in a September 2002 public offering. (See BioWorld Today, Oct. 10, 1997, and Sept. 30, 2002.)
The company's stock (NASDAQ:TRMS) dropped 13 cents Tuesday to close at $9.78.