The National Institute for Health and Clinical Excellence (NICE) said on Friday it was rejecting the drug for patients whose breast cancer has spread to other parts of the body due to “uncertain evidence.”

Avastin, whose generic name is bevacizumab, is also licensed as a treatment for a number of other cancers — but it has not been approved by NICE for use in any of these.

It is widely used for treating bowel, lung, breast and kidney cancer in other countries and had worldwide sales of 6.2 billion Swiss francs ($5.90 billion) last year.

Draft guidance from the agency, which decides if drugs should be paid for by the country’s taxpayer-funded National Health Service (NHS), concluded that evidence on Avastin did not show it significantly improved or extended lives in breast cancer.

“The clinical trial results for bevacizumab were disappointing in that they were unable to prove definitively that the drug could extend the lives of patients with metastatic breast cancer over and above currently available treatments,” said NICE Chief Executive Andrew Dillon.

The NICE ruling comes ahead of a Food and Drug Administration advisory panel meeting on Avastin on July 20, when experts will consider whether or not to endorse full approval of the medicine in breast cancer in the United States.

Roche said its drug, when added to chemotherapy, had been shown to reduce the risk of a woman’s disease progressing by half and it would work with the British government to explore all possible ways of making Avastin available to patients.

A company spokeswoman said Roche had submitted a patient access scheme to NICE, which would place a cap on the amount the NHS would pay for the treatment of each woman. The plan has not yet been included in NICE’s evaluation as it is still pending approval from the Department of Health.

NICE also decided in separate draft guidance not to recommend Takeda’s bone cancer drug Mepact, or mifamurtide, because of uncertainties over its effectiveness and its high cost.

Source: Reuters

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Data from the AVADO study, a Phase III trial of the drug combination in 736 patients, showed improvement in progression-free survival with use of the drug in combination with Taxotere, compared with Taxotere alone.

Avastin is approved in the EU for first-line treatment of patients with advanced breast cancer in combination with paclitaxel, and for the treatment of advanced stages of colorectal, kidney, and non-small-cell lung cancers.

Source: FirstWord

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In the study, 10 patients with progressive NF2 and progressive vestibular schwannomas who were not candidates for standard treatment with surgery or radiation were administered Avastin intravenously every two weeks for a median duration of 12 months. Researchers found that treatment resulted in tumour shrinkage in nine patients. Six individuals achieved a decrease in tumour volume of at least 20 percent from baseline, with four maintaining the response during 11 to 16 months of follow-up, investigators noted.

Additionally, the study found that of the seven patients who began losing their hearing prior to the start of the trial, four regained some hearing, which was maintained for up to 16 months, while two had stable hearing and one experienced progressive hearing loss.

Plotkin indicated that based on the study’s results, researchers have started recruiting patients for a clinical trial of PTC Therapeutics’ VEGF inhibitor, PTC299, as a potential treatment for NF2. The oral compound, Plotkin said, may be easier to administer than Avastin and may also cause fewer side effects.

Source: FirstWord

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Avastin is already approved in Europe, in combination with paclitaxel, as a first-line treatment for patients with metastatic breast cancer. The drugmaker said the positive opinion for the combination of Avastin plus Taxotere was based on Phase III data from the 736-patient AVADO study, which showed that those given Avastin plus sanofi-aventis’ chemotherapy drug experienced increased progression-free survival, compared with Taxotere alone.

Avastin is also cleared for use in Europe to treat advanced stages of colorectal, kidney, and non-small-cell lung cancers.

Source: FirstWord

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In April, Pfizer stopped a late-stage trial comparing Sutent to standard-of-care in advanced breast cancers citing a similar inability to significantly improve progression-free survival. Even with these first results from a program evaluating a combination therapy not showing an improvement, the firm says that it will continue on its path to evaluate Sutent in various regimens against solid tumors.

Sutent is already approved for gastrointestinal stromal tumors and advanced/metastatic renal cell carcinoma. It is in a slew of mid- to late-stage studies including advanced non-small-cell lung cancer, advanced colorectal cancer, advanced hepatocellular carcinoma, and advanced hormone-refractory prostate cancer.

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The latest trial to be stopped was evaluating Sutent plus paclitaxel versus bevacizumab plus paclitaxel. Ongoing Phase III trial investigations in advanced breast cancer include Sutent plus docetaxel versus docetaxel for first-line treatment and another looking at Sutent plus capecitabine versus capecitabine for second-line treatment. Analysis from both is expected by the end of the year or early next year.

Source: GEN News

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The C-08 study involved 2710 patients with surgically-resected stage II or III adenocarcinoma of the colon who received either six months of treatment with chemotherapy alone, or six months of treatment with chemotherapy plus Avastin followed by six months of Avastin monotherapy. After a follow up of three years, findings demonstrated that 77.4 percent of patients in the Avastin arm were free of disease, compared with 75.5 percent of those in the control group. The result was not statistically significant, but lead investigator Norman Wolmark noted that Avastin reduced the risk of cancer recurrence or death by about 40 percent at the one-year mark.

Philippe Bishop, head of clinical development at Roche’s Genentech unit, explained that “as patients come off treatment, the events come back…The one-year duration of treatment was insufficient to derive clinical benefit.” Wolmark stated that “these results suggest longer durations of Avastin treatment should be considered for future studies in early-stage colon cancer to further reduce the risk of the cancer coming back,” and he added that researchers hope to begin a trial in the near future using Avastin for a two-year treatment period.

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A separate late-stage study of Avastin in the adjuvant setting in early-stage colon cancer is in progress, with results expected next year. Bishop indicated that the results from the C-08 study are influencing Roche’s and Genentech’s ongoing clinical trial programme for the drug, which includes use in early-stage breast cancer and non-small-cell lung cancer.

Source: FirstWord

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The drugmaker said the effectiveness of the drug for this indication is based on an improvement in objective response rate from a Phase II study, and noted that no data are currently available from randomised controlled trials demonstrating increased survival or an improvement in disease-related symptoms. “A global Phase III trial in patients with newly diagnosed glioblastoma will soon begin enrollment to further evaluate Avastin in this setting,” said Genentech chief medical officer Hal Barron.

In Genentech’s statement, Timothy Cloughesy, director of the Neuro-Oncology Program of the JonssonComprehensive Cancer Center at the University of California, noted that “people with this type of brain cancer have had no new treatments in more than a decade.”

Source: FirstWord

Genentech’s chief medical officer Hal Barron stated that “while we are disappointed the C-08 study did not meet its primary endpoint, our initial review of the data leads us to continue to believe Avastin may be active in patients with early-stage colon cancer.” He added that the companies “remain fully committed to the ongoing Avastin adjuvant programmes in early-stage colon, breast and lung cancers.” The findings from the trial have been submitted for presentation at the upcoming American Society of Clinical Oncology annual meeting.

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Commenting on the news, analyst Roland Maier of BB Biotech called the results “a major setback for Roche…The use of Avastin in the adjuvant setting was a major part of the growth strategy. It can still be a very significant product, but there had been expectations that adjuvant could double sales of the drug.” However, Karl-Heinz Koch of Helvea noted that “the headlines are negative, but it may not be as much doom and gloom as it seems now.” He said the drugmakers’ statements “suggest that the results are not as horrible as they seem and imply they saw a trend towards statistical significance, so there may be a subset of people for which it is beneficial.” He added that “it was always going to be difficult for the trial to succeed…Avastin relies on synergistic activity with chemotherapy, which works better in patients with a larger tumour mass and that benefit diminishes when you apply it to smaller tumours.”

The head of Roche’s pharmaceuticals division, William Burns, indicated that Avastin still has the potential for sales of as much as 9 billion Swiss francs by 2011. Revenue for the drug was 5.2 billion francs ($4.5 billion) in 2008.

Source: FirstWord

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The drugmaker said the approval was based on results from the late-stage E4599 trial involving 878 patients, which showed that those who took Avastin plus chemotherapy achieved median survival of 12.3 months, compared to 10.3 months for those who took chemotherapy alone.

Avastin is already approved in Canada to treat metastatic colorectal cancer and advanced breast cancer.

Source: FirstWord

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The application for accelerated approval was based on a Phase II, non-comparative study of 167 patients with previously treated glioblastoma who took Avastin alone, or Avastin plus chemotherapy. Data from the group of 85 patients who took Avastin alone showed that tumours were reduced to at least half their original size in 28 percent of the cases, and that in those who had a reduction, half had a response of at least 5.6 months. In addition, 43 percent of the 85 patients lived for six months without disease progression, half lived at least 9.3 months after starting treatment, and 38 percent lived longer than one year.

Panel member Michael Link noted that Avastin is “substantially better than almost anything else” that has been approved for the disease in the past 30 years, while panellist Jay Loeffler described the results as “dramatic.” Overall, committee members indicated that they believed the data submitted by Genentech demonstrated the drug was likely to either prolong or improve patients’ lives.

David Schenkein, senior vice president of clinical haematology and oncology at Genentech, a wholly-owned subsidiary of Roche, said “we’re confident that we have met the criteria for accelerated approval.” He added that the company plans to begin a Phase III study of Avastin later this year in patients newly diagnosed with glioblastoma multiforme, and full results are expected in 2014.

Source: FirstWord