Tivozanib (AV-951)

The formation of new blood vessels, known as angiogenesis, is required to support certain important natural processes such as embryonic development, reproduction and wound healing. Angiogenesis also plays an important role in cancer progression and the spread of tumors within the body, or metastasis. Tumors cannot grow beyond a small size in the absence of the formation of new blood vessels. Because essentially all solid tumors require angiogenesis to progress beyond microscopic size, anti-angiogenesis drugs have demonstrated benefit in a wide variety of tumor types.

 

Tivozanib, our lead product candidate, is a highly potent and selective oral inhibitor of the vascular endothelial growth factor, or VEGF, receptors 1, 2 and 3. AVEO believes that tivozanib’s favorable efficacy and safety profile increases its potential to be combined with other anti-cancer agents in a manner that may produce better clinical outcomes. As a result, we have a number of clinical trials underway that are designed to test tivozanib in combination with other drugs and chemotherapies in multiple solid tumor types. We are also utilizing our Human Response Platform to help identify rational drug combinations and patient populations most likely to be responsive to these combination therapies. We expect that the results of these clinical trials, together with the results of our ongoing research efforts, will help to inform our clinical development plans for tivozanib in additional indications.

 

AVEO recently completed a successful 272-patient phase 2 clinical trial of tivozanib in advanced RCC. In this trial, we measured, among other things, each patient’s progression-free survival, which refers to the period of time that began when a patient entered the clinical trial and ended when either the patient died or the patient’s cancer had grown by a specified percentage or spread to a new location in the body.   

 

The overall median progression-free survival of patients in the phase 2 trial was 11.8 months. The incidence of side effects in the trial such as diarrhea, fatigue, rash, mucositis, stomatitis and hand-foot syndrome, which are commonly associated with other VEGF receptor inhibitors, was notably low, with moderate to severe episodes of these side effects occurring in fewer than two percent of treated patients.

 

 

 

In a retrospective analysis of the subset of 176 patients in our phase 2 clinical trial who had the clear cell type of RCC and who had undergone a prior nephrectomy, both of which are inclusion criteria for our phase 3 clinical trial of tivozanib, the median progression-free survival was 14.8 months.

 

 

More than 80% of patients who received tivozanib therapy in the phase 2 clinical trial experienced some degree of tumor shrinkage while on therapy as shown below.

 

 

 

AVEO has initiated patient enrollment in our Phase 3 clinical trial for tivozanib in RCC. Based on the data we have received to date, we believe that tivozanib may offer a therapeutic alternative for the first-line treatment of advanced RCC. 

 

In addition to our ongoing Phase 3 clinical trial of once-daily, oral tivozanib in patients with advanced RCC, we are currently conducting multiple clinical trials of tivozanib including:

 

• a phase 1b clinical trial in combination with Torisel (temsirolimus), an approved inhibitor of the receptor known as mammalian target of rapamycin, or mTOR, in patients with advanced RCC;
• a phase 1b clinical trial in combination with the FOLFOX6 chemotherapy regimen in patients with advanced colorectal cancer and other gastrointestinal cancers;
• a phase 1b clinical trial in combination with paclitaxel in patients with metastatic breast cancer; and,
• a phase 1b clinical trial as a monotherapy in patients with non-small cell lung cancer.

We expect that the results of these clinical trials will help to inform our clinical development plans for tivozanib in additional indications.

 

 

 

 

In January 2007, AVEO licensed exclusive rights to develop and commercialize tivozanib (originally KRN951) in all territories outside of Asia from Kyowa-Kirin, formerly Kirin Brewery Co. Ltd.

Patients are invited to visit www.clinicaltrials.gov for more information regarding tivozanib clinical trials.