US HIV community hold productive meeting with Schering-Plough on new anti-HIV entry inhibitors SCH-C and SCH-D

Schering-Plough is developing two anti-HIV drugs – SCH-C and SCH-D* – from the new class of antiretrovirals known as entry inhibitors. In early studies this drug class has shown great promise for the treatment of HIV.

Members of two HIV community treatment advocacy groups, the Coalition for Salvage Therapy (CST) and the AIDS Treatment Activists Coalition (ATAC) met with Schering-Plough representatives in Chicago on August 28, 2002 to discuss the development status of the HIV entry inhibitors SCH-C and SCH-D, which are in early stage clinical studies.

The first and farthest advanced HIV entry inhibitor candidate is Fuzeon (enfuvirtide; T-20) from Roche Pharmaceuticals. Fuzeon is now in Phase III trials and is expected to win FDA approval by the spring of 2003.

Early data on SCH-C comes from tests in 52 healthy, HIV negative volunteers and a Phase I study in 24 HIV positive volunteers. The major advantage of the two new Schering drugs is their ability to block HIV from binding to the CCR5 ** receptor on key immune cells, thereby preventing the virus from entering these cells and establishing infection. Currently available anti-HIV drugs do not have the ability to prevent infection of human cells, but only to suppress HIV replication once the virus has already entered these cells.

Another important advantage of the Schering drugs is that they are taken orally (capsule, tablet or pill formulation), which will help to increase adherence and maintain a higher quality of life. In contrast, the Roche entry inhibitors are administered by subcutaneous injection, which may limit adherence and quality of life.

Finally, the Schering entry inhibitors so far have shown no apparent adverse side effects of great concern. Headache is the most commonly reported side effect. However, one potentially worrisome effect of these drugs is that they may cause a type of heartbeat irregularity known as “QT prolongation”, a characteristic of about 50 other known FDA-approved drugs. So far, researchers have not noted a dangerous level of QT prolongation in study volunteers using SCH-C. Study participants are being carefully monitored for any increase in this effect, which can then be reversed quickly. Bob Roehr discusses the QT phenomenon in more detail in his meeting notes below.

SCH-C is about to enter Phase II trials. The primary objectives of the Phase II studies will be to establish the dose of SCH-C that produces the strongest anti-HIV activity (reduction of HIV viral load, increase in CD4 counts, etc) while still offering safety. Phase III trials will then begin to evaluate efficacy of the drug more fully. It is possible that SCH-D could prove to be the more promising of the two compounds, in which case SCH-D may be the candidate Schering elects to develop commercially. However, the company left open the potential for developing both SCH-C and SCH-D.

Community participants were pleased and relieved to hear that Schering Plough supported the community’s wish to see an SCH-C Expanded Access programme for 2,000 – 10,000 patients planned and ready to move forward at about the same time as the beginning of the Phase III trial, assuming that the drug lives up to its early promise