There may yet be a positive outcome to Genetech's once-failing cancer drug, after the company announced "encouraging" Phase II trial results.
The trial tested pertuzumab, formerly known as Omnitarg, in conjunction with Eli Lilly 's Gemzar (gemcitabine), compared with Gemzar alone, in patients with ovarian cancer.
Pertuzumab, a humanised monoclonal antibody, is the first in a new class of HER dimerisation inhibitors (HDIs). The HER signalling pathway is thought to be significant in the growth and formation of several different cancer tumours and there are several drugs on the market that target this process.
Jason Kantor, an analyst at RBC Capital Markets, said that although the results are positive overall, Genentech officials confirmed in an interview that the drug did not meet its goal of producing a statistically significant improvement in progression-free survival. Genentech denies this, saying the trial was aimed at merely estimating survival rates.
What sets pertuzumab apart from other HER drugs such as Genentech and Roche's big selling Herceptin (trastuzumab) is that it works much earlier, before HER2 levels become high whereas other drugs were designed to specifically take advantage of the increasingly high levels of HER2 found in patients with advanced or relapsed cancer tumours.
This markedly increases the possible number of users, which is good news for patients, Genentech and Roche, who co-develop the drug. However, pertuzumab has not always shown such encouraging signs while in development.
Despite positive preliminary Phase I results in 2003 in patients with ovarian, prostate and breast cancer, the drug, given on its own, two years later the drug had failed a Phase II trial in the same cancers.
The best results came in patients with ovarian cancer where 15 per cent of patients responded to treatment, leading the two companies to initiate these further tests on pertuzumab in a combination treatment.
"Advanced ovarian cancer continues to be a difficult-to-treat cancer with few approved treatment options, " said Hal Barron, Genentech's chief medical officer. "We are encouraged by the results of this trial, and will continue to analyse the data to help determine next steps for the pertuzumab development programme."
Pertuzumab binds to a HER2 receptor and prevents it from forming a pair with another member of the HER family. HER2 is a member of the epidermal growth factor receptor (EGFR) family and is found in several types of cancer, although it is most commonly associated with breast cancer.
Herceptin has approved in combination with Taxol (paclitaxel) for use in breast cancer patients. Herceptin is another mAb product but is only effective in tumours where there are increased levels of HER2. Compared to the same period in 2005, in the first nine months of 2006, sales of the antibody in the US have increased 40 per cent to $912m (€700m).
Historically, there have also been safety concerns over HER targeting drugs. Herceptin can result in reduced heart function or even heart failure.
One of the 21 patients being studied in the 2003 Phase I study of pertuzumab had a heart attack and in the 2005 Phase II trial in breast cancer, seven of 78 patients showed a drop in left ventricular ejection fraction. There was also one case of congestive heart failure in the study.
Genentech has announced that in this latest trial, no new or unexpected safety signals were seen. There was one case of congestive heart failure reported.
If approved, Genentech and Roche could use pertuzumab alongside another of their drugs already on the market. Avastin (bevacizumab) is a recombinant humanized antibody designed to inhibit Vascular Endothelial Growth Factor (VEGF), a protein that plays a critical role in the formation of new blood vessels in a tumour.
Avastin is currently approved for use in colon and rectum cancer and is in late stage trials for, breast, kidney, non-small cell lung, prostate and ovarian cancers.
Genentech will announce full details from the pertuzumab trial a later date. The drug is also currently in Phase II trials for metastatic breast cancer.