Ibalizumab (TMB-355)

Ibalizumab is a humanized monoclonal antibody (mAb) and a member of an emerging class of HIV therapies known as viral-entry inhibitors. This drug candidate is distinct from other entry inhibitors in that it binds to the CD4 molecule, the primary receptor for HIV infection, thereby interfering with the penetration of the virus into the cell. It is the first entry-blocking humanized mAb to treat HIV/AIDS.

Ibalizumab caught the attention of the scientific community in February 2003, when results from the phase-1, single-dose clinical trial showed a transient but clinically significant reduction in the patients’ viral load. Moreover, it was well tolerated with no evidence of adverse effects on CD4 T-cells of treated subjects unlike the majority of approved drugs for HIV. The U.S. FDA granted Ibalizumab fast track status in October 2003.

The phase-2a clinical trial was successfully completed in 2006, with the results showing a clean safety profile and clear antiviral activity (10-fold reduction in viral load). After the FDA revised the clinical trial guidelines in 2007, TMB devised a new phase-2b protocol which has been submitted and approved by the FDA. A 120-patient trial is well underway that will complete enrollment by 3Q 2009. TaiMed Biologics is concurrently looking into formulating a subcutaneous injection dosage form and a phase 1 human pharmacokinetics bridging study is expected to be completed in the second half of 2010. TMB intends to seek a partner for phase 3 development which is expected to begin by 2011 using multinational clinical sites including Taiwan. The company plans to file BLA for Ibalizumab to the U.S. FDA and to launch the commercial product by the end of 2013.

Phase 2a Study Design and Results

The phase 2a study is a multi-center, randomized, double-blind, placebo-controlled trial to compare safety and efficacy of two doses of Ibalizumab against placebo among 82 treatment-experienced HIV positive patients.

Ibalizumab in combination with OBR (optimized background regimen) resulted in statistically significant viral load reduction compared to placebo plus OBR. Dosing at 10 mg/kg led to a decrease in viral load was associated with a statistically significant and clinically meaningful increase in CD4+ T cells.

Ibalizumab was well tolerated with no infusion-site reactions, no serious adverse events, and no laboratory abnormalities. In addition, good patient adherence to study visits and acceptance of intravenous administration were observed.

Phase 2b Clinical Trial

A 120-patient trial Phase 2b clinical trial is currently ongoing.  The primary evaluation of effectiveness will be based on the proportion of patients achieving undetectable viral loads at week 24.  Secondary objectives include evaluation of changes in viral load, CD4+ cell counts, TOLVR, PK sensitivity, susceptibility and safety.  We anticipate completion of the study in 1H 2010.