First T-20 study in children - Injectable T-20 tolerable - rapid and potent viral suppression achieved with promising safety profile
First T-1249 human study shows potent viral suppression in patients resistant to current therapies
Basel, 19 December 2001 � The first paediatric study provides an early indication that T-20 is likely to be well tolerated in children. The potent and rapid viral suppression that was observed in children aged between three and twelve years brings fresh hope for children with HIV.
T-20 is the first in a new class of investigational drugs called fusion inhibitors and it works by preventing the HIV virus from �fusing� with the host cell and taking it over. T-20 cannot be taken orally as it would be destroyed by digestive enzymes in the gut. As such the drug has to be administered by injection under the skin twice a day.
Fourteen HIV-infected children, ages four to 12, were evaluated in a Phase I/II study being conducted in collaboration with the Pediatric AIDS Clinical Trials Group (PACTG) of the National Institute of Allergy and Infectious Diseases and the National Institute of Child Health and Human Development Pediatric/Perinatal HIV Clinical Trials Network. The study co-chairs are Dr. Coleen Cunningham of SUNY Upstate Medical University in Syracuse NY who presented the data and Dr. Joseph Church of Children's Hospital Los Angeles in Los Angeles CA.
The preliminary findings suggest that short-term (up to 24 weeks) subcutaneous dosing with T-20 is well tolerated by children and that in the highest dose group (60 mg/m2), T-20 resulted in an approximate 10-fold average reduction from baseline HIV RNA levels in seven days. T-20 in combination with other antiretrovirals resulted in continued virologic suppression through 24 weeks, with 43% (6/14) of the treatment-experienced children enrolled having HIV viral load below the level of detection (<400 copies/mL). One child discontinued due to aversion to injections but no child discontinued due to adverse events. Mild to moderate injection site reactions occurred in a majority (11/14) of children.
Leading a Keynote Session at the conference, John P. Moore, Ph.D., Professor of Microbiology and Immunology at Cornell University�s Weill Medical College and leading expert in the process of HIV entry, discussed Fusion Inhibitors and his research into the processes by which HIV attaches to, and fuses with, host cells.
�We�re learning more and more about potential targets in the viral lifecycle to disarm the virus, including the blocking of viral fusion,� reports Dr Moore. �Novel antiretrovirals that disrupt this step in viral entry may become an important addition to the HIV treatment mix.�
T-1249 demonstrates viral suppression in patients resistant to current therapies
Results from the first human clinical trial evaluating T-1249 indicate that Roche and Trimeris� novel Fusion Inhibitor may prove to offer vital support for people living with HIV who have developed resistance to all current classes of antiretroviral agents. In this study, T-1249, the follow-up Fusion Inhibitor to T-20, showed dose related suppression of HIV in patients who had already developed resistance to all three classes of currently available antiretroviral (ARV) drugs - nucleoside reverse transcriptase inhibitors, protease inhibitors and non-nucleoside reverse transcriptase inhibitors.
�Like T-20, this new drug T-1249 is active in people who have developed multiple resistance and is great news for patients in need of new treatment options,� said Diego Miralles, M.D., Director of Clinical Trials for Trimeris.
�The growing challenge of HIV drug resistance could never be more apparent. On a regular basis we are alerted to the increasing spread of drug resistant HIV and it is clear that significant attention and investment are urgently needed to continue the development of new drugs to address this problem� said Dr. David Reddy, Franchise Leader & Disease Area Strategy Head-HIV/AIDS, Roche. � T-20 is in its final stages of development and T-1249 is in its early stage of development. We hope that they will both expand the armamentarium against HIV and help increase future treatment options for people living with HIV�.
The early investigational study (phase I/II) has reported the results from 63 HIV positive adults who were heavily experienced to ARVs (on average patients had already experienced ten ARVs). Patients received T-1249 with no other simultaneous antiretroviral therapy for 14 days at doses ranging from 6.25 to 50mg/day on a once or twice daily regimen. Dose dependant decreases in viral load were observed and on day 14, the average (median) change from baseline ranged from - 0.10 to -1.40 log10 copies of viral RNA per mL for 6.25mg/day and 50mg/day respectively. Importantly, the antiviral activity of T-1249 in vivo in this study was unaffected by prior exposure to available ARV�s or by multiple resistance mutations to other antivirals. The baseline genotyping (variable washout period) showed that 48% of patients had relevant mutations to the three currently approved classes of antiretroviral agents. Based on the favourable activity and tolerability results observed with T-1249, Roche and Trimeris are continuing to explore higher doses in this ongoing study.
ENDS
Additional information:
T-20/ T-1249 Presentations at ICAAC
Antiretroviral Therapy II, 194, Tuesday, Dec. 18, 3:00 p.m. - 4:30 p.m.
Abstract 1942: �Chronic Subcutaneous T-20 in HIV-1 Infected Children: Safety and Anti-Viral Activity�
The preliminary findings suggest that short-term (up to 24 weeks) subcutaneous dosing with T-20 is well tolerated by children. In the highest dose group (60 mg/m2), T-20 containing therapy caused rapid suppression of HIV RNA of approximately 10-fold average reduction from baseline levels in seven days. Dose ranging studies are ongoing.
Antiretroviral Therapy II, 194, Tuesday, Dec. 18, 3:00 p.m. - 4:30 p.m.
Abstract 1936: �Comparative Pharmacokinetics of Carbonate (CO3) and Tris Buffer Formulations of the Peptide HIV Fusion Inhibitor T-20�
Data from this study indicate that T-20 can be administered via subcutaneous injections delivered as one injection twice daily, rather than by two injections twice daily, a procedure used in earlier clinical studies.
HIV Session I, 071, Monday, Dec. 17, 8:30 a.m. � 11:00 a.m.
Abstract 669: �Genotypic Resistance to Protease and Reverse Transcriptase Inhibitors and Antiretroviral History Do Not Affect Virologic Response to T-1249�
An analysis of the T-1249 Phase I/II dose-ranging clinical trial (T1249-101) suggests that daily dose of T-1249 � and not prior antiretroviral treatment experience, including mutations to all approved classes of HIV drugs � was the only variable that was associated with the viral load reduction among treatment-experienced patients.
Notes to editors:
Meeting the Growing Need For a New Class of HIV Drugs
One of the biggest challenges facing people living with HIV is resistance to currently available therapies. Thirty to fifty percent of patients have a strain of the virus that has developed resistance to a number of the various antiviral treatments and the therapy options available to them are therefore reduced. Roche and Trimeris are committed to discovering and developing treatments for patients in need of new options and are planning to invest approximately half a billion US dollars to bring the fusion inhibitors to people living with HIV/AIDS.
Long-Term Commitment to HIV Research and Development
Roche and Trimeris are working together to mobilize the considerable resources required to support the rapid development of T-20 and T-1249, the first members of a new class of investigational anti-HIV drugs known as Fusion Inhibitors. T-20, currently in Phase III clinical trials is the furthest along in clinical development in the entry inhibitor class while T-1249 is currently being evaluated in early Phase I/II clinical trials. Unlike existing AIDS drugs that work inside the cell and target viral enzymes involved in the replication of the virus, T-20 and T-1249 block fusion of HIV with host cells before the virus enters the cell and begins its replication process. In June 2001, Roche and Trimeris announced a joint research agreement to identify and develop additional HIV Fusion Inhibitor Peptides.
T-20 and T-1249 have fast track designation from the FDA in the US for the treatment of HIV-infected individuals. Fast track is granted to facilitate the development and expedite the review of applications for drugs that are intended to treat serious or life-threatening disease and that demonstrate the potential to address an unmet medical need
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world�s leading research-oriented healthcare groups in the fields of pharmaceuticals, diagnostics and vitamins. Roche�s innovative products and services address needs for the prevention, diagnosis and treatment of disease, thus enhancing people�s well-being and quality of life. For more information on Roche and its commitment to research in HIV, visit the roche-hiv.com website.
About Trimeris Inc.
Trimeris is a development stage, biopharmaceutical company engaged in the discovery and development of novel therapeutic agents that block viral infection by inhibiting viral fusion with host cells. Trimeris� lead product candidate, T-20, inhibits fusion of the human immunodeficiency virus (HIV) with host cells. T-20 is being co-developed with Roche and is currently in Phase III clinical trials. Trimeris and Roche are also co-developing a second HIV fusion inhibitor drug candidate, T-1249, that is in Phase I/II clinical testing. For more information on Trimeris, Inc., visit the company's website at
