Cancer + Avastin
FDA Update - Avastin (bevacizumab)
WARNINGS AND PRECAUTIONS
Source : FDA (Dec 2013)
Researchers Detail Possible Resistance Mechanisms of Colorectal Cancer to Bevacizumab (Avastin)
A University of Colorado Cancer Center study published in the journal PLoS One shows that when colorectal cancer is targeted by the drug bevacizumab (Avastin), tumors may switch dependence from VEGF-A, which is targeted by the drug, to related growth factors in including VEGF-C, VEGF-D and placental growth factor. This change to new growth-factor dependence may allow colorectal cancer to push past bevacizumab’s blockage of VEGF-A to continue to drive tumor growth.“Think of it like damming a river. Bevacizumab can block the main flow, but then once a tumor’s need builds up behind this dam, water starts to flow around the blockage in the form of streams and tributaries. That’s like these other growth factors – eventually a tumor becomes able to use these tributaries of VEGF-C, VEGF-D and placental growth factor to supply itself with the ‘water’ it needs,” says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of Medical Oncology at the University of Colorado School of Medicine.
The analogy of liquid is an apt one – bevacizumab slows cancer’s growth by limiting a tumor’s ability to grow the new blood vessels it needs to supply itself with nutrients. Especially in combination with chemotherapy, bevacizumab has proved an effective treatment for colorectal cancer. But then there frequently comes a point at which bevacizumab stops working and the tumor restarts its growth. This study asked why.
Specifically, Lieu and colleagues serially tested the levels of other VEGF-related growth factors in 42 patients treated with bevacizumab and chemotherapy, at many points during the course of their treatment.
“What we saw is that levels of VEGF-C and placental growth factor went up just before tumors progressed and then stayed high during the periods of tumor growth. Interestingly, VEGF-D was only elevated during progression. But it seems that tumors may be using these growth factors as ways to create blood vessel growth in the absence of VEGF-A, blocked by bevacizumab,” Lieu says.
Then the researchers also took a snapshot of levels in 403 colorectal cancer patients, at one time during treatment. Because this group included patients who were and were not being treated with chemotherapy along with bevacizumab, they could show that the rise in VEGF levels was, in fact, due to bevacizumab and not to some interaction with the chemotherapy.
“It’s too early to say with certainty that VEGF-C, VEGF-D, and placental growth factor are the cause of colorectal cancer resistance to bevacizumab, but the correlation we saw in this study is compelling,” Lieu says.
Current studies are exploring the use of drugs that block more blood-vessel-growth-promoting factors than VEGF-A. For example, Lieu points to the example of aflibercept (Zaltrap), which was given FDA approval in August, 2013 for the treatment of metastatic colorectal cancer, along with the chemotherapy regimen known as FOLFIRI. The drug inhibits placental growth factor along with VEGF-A.
“It’s an attractive strategy, and also proof of concept that by targeting not only the primary mechanism of tumor growth but also one or more of these ‘workarounds,’ this drug or other future drugs could stall growth longer than blocking any one of these growth factors, individually,” Lieu says.
Lieu points out that in addition to targeting these additional growth factors, the fact that spikes in VEGF-C and placental growth factor presage tumor progression could give doctors and researchers a clue that bevacizumab has lost its efficacy. Though more work is needed, Lieu can imagine using spikes in VEGF-C or prenatal growth factor to recommend evaluating new treatment options.
Source : Newswise
Link to Source
More Bad News for Avastin in Breast Cancer
A randomized trial found bevacizumab (Avastin) failed to improve outcomes in combination with chemotherapy in early triple-negative breast cancer, adding to the string of failures for the drug.Invasive disease-free survival (DFS) and preliminary overall survival (OS) results showed no significant advantage to the addition of bevacizumab compared with adjuvant chemotherapy alone, David Cameron, MD, of Edinburgh University in Scotland, and colleagues reported in the BEATRICE trial.
But there was some good news: The researchers found outcomes were somewhat better than the literature would suggest for this group of patients not responsive to estrogen-, progesterone-, or HER2-targeted agents, with 83% to 84% without invasive cancer recurrence at 3 years.
"But in terms of improvement in outcomes, giving 1 year of bevacizumab isn't the answer," he said at a San Antonio Breast Cancer Symposium (SABCS) press conference.
The findings followed on the heels of negative results at the same meeting from the LEA trial suggesting no benefit to bevacizumab as an add-on to hormonal therapy in advanced breast cancer.
The drug lost its approval for use in breast cancer late last year, after studies required by the FDA as a condition of its fast-track indication in metastatic HER2-negative breast cancer failed to confirm even much of a progression-free survival advantage.
"It's getting to the point where it's going to be difficult to know the role of bevacizumab, if any, in breast cancer," commented C. Kent Osborne, MD, of Baylor College of Medicine in Houston, who moderated the SABCS press conference.
"If it's going to work, you would think it would work in this situation," he explained. "What we're dealing with at that stage are microscopic metastases that haven't developed a sufficient blood supply yet. If you can prevent that blood supply from forming, you might have a more dramatic effect than in already established tumor like in metastatic breast cancer."
Osborne called the BEATRICE results disappointing and suggested a limited role for the drug unless other ongoing studies show otherwise.
The trial included 2,591 women with centrally confirmed triple-negative invasive early breast cancer starting adjuvant chemotherapy with a taxane or anthracycline or both.
The women were randomized to four to eight cycles of the physicians' choice of those cytotoxics either alone or with the addition of 5 mg/kg per week bevacizumab, which was continued afterward for a total of 1 year of treatment.
For the primary endpoint, invasive DFS rates were 83.7% with bevacizumab compared with 82.7% in the control group, for a hazard ratio of 0.87 (P=0.181). Invasive DFS was selected as the primary endpoint, "just as a check to make sure we're not inducing cancers in other areas," Cameron explained.
Interim OS results, with only 59% of the planned number of events accrued, suggested a similar hazard ratio of 0.84 for bevacizumab compared with chemotherapy alone (P=0.232).
An adequately-powered comparison of survival is expected in about a year, Cameron noted, though he said the results at least clearly show no evidence of harm.
Toxicity followed the known profile of the drugs. The analysis paid particular attention to cardiovascular risks, which Cameron noted have been of particular concern with bevacizumab, similar to trastuzumab (Herceptin).
A prospectively-measured ejection fraction drop of at least 10% to fall under the entry criteria threshold of 50% was more common in the bevacizumab group. NYHA class III or IV heart failure occurred in 0.5% and 0.6% of patients, respectively, without any cases in the chemotherapy alone group.
But about 80% of clinically-significant heart failure cases recovered.
"Yes, there are changes in ejection fraction, there is a low rate of more severe heart failure, but this is not outside of what we would have expected with this drug," Cameron concluded
Source : MedPage Today via San Antonio Breast Cancer Symposium Cameron D, et al "Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer" SABCS 2012; Abstract S6-5.
Link to Source
VA puts cork in Avastin use for eye disease
VA hospitals won't be giving patients Avastin to treat an eye disease. In the latest development in the controversial use of Roche's cancer drug for wet age-related macular degeneration, the Department of Veteran Affairs, one of the largest healthcare providers in the U.S., has pulled the plug on the off-label use of the drug for the blindness-causing ailment.
The VA's decision comes amid pressure from members in Congress to get Medicare to back Avastin's use for the eye disease. The drug is just a fraction of the cost of Roche's approved medicine for the eye ailment, Lucentis, but cases of serious eye infections linked to the off-label use of Avastin have raised questions about whether the low-cost option is the best for patients. The VA is investigating the Avastin option for macular degeneration.
"The Department of Veterans Affairs (VA) has ceased ophthalmologic use of Avastin pending the results of an ongoing investigation and will advise its physicians to consider alternate therapies," the VA announced, as quoted by Reuters. "Once the investigation is complete, VA will reassess how Avastin and similar therapies may be made available for ophthalmologic use and will issue further guidance."
This was good news for Regeneron ($REGN). Shares the Tarrytown, NY-based developer, which is close to a potential approval for a rival drug for the eye disease called Eylea, jumped on news about the VA's decision yesterday and hit a 20-year high during afternoon trading. A panel of experts unanimously supported approval of Eylea this summer, and the FDA is expected to make its decision on the drug by November, Reuters reported.
Another issue facing Avastin is that compounding is required before doctors can use the cancer med to treat the eye disease. "The question is whether the VA is comfortable from this point onwards using an off-label product that needs to be compounded by the pharmacy," Yaron Werber, an analyst with Citigroup, told Bloomberg. The analyst added that new regulations for the compounding process could also affect the drug's off-label use.
Source : Fierce Pharma
Link to Source
More eye patients go blind after Avastin injections
There's another cluster of eye infections, some causing blindness, in patients using Avastin for macular degeneration. This time, the cases cropped up at a Veterans Affairs facility in Los Angeles; 5 people who were injected with Avastin lost vision in the treated eye.
The Genentech cancer drug isn't approved for use in the eye. But ophthalmologists have turned to it as a cheaper alternative to Genentech's Lucentis drug for wet age-related macular degeneration. It costs around $50 per injection, compared with $2,000 or so for the purpose-built drug.
The four LA infections join four at a VA hospital in Nashville and another cluster of 12 in the Miami area. As Reuters notes, Genentech--now owned by Roche--has for years argued that repackaging Avastin into doses small enough for eye use risked contamination. The company moved several years ago to restrict distribution to cut down on Avastin repackaging, but compounding pharmacies continue to prepare doses for ophthalmic use.
That could change, and given the big price difference, it could be a boon for Genentech, but a cost burden for Medicare, which saves big bucks thanks to this off-label Avastin use. The Los Angeles VA has already suspended use of Avastin for macular degeneration and is turning to Lucentis instead, the New York Times reports.
Source : Fierce Pharma
Link to Source
FDA panel: Revoke drug's breast cancer approval
A panel of cancer experts has ruled for a second time that Avastin, the best-selling cancer drug in the world, should no longer be used in breast cancer patients, clearing the way for the government to remove its endorsement from the drug.
The unprecedented vote Wednesday by the Food and Drug Administration advisory panel comes less than a year after the same panel reached the same conclusion.
The six members of the FDA oncology drug panel voted unanimously that Avastin is ineffective, unsafe and should have its approval for breast cancer withdrawn.
"I think we all wanted Avastin to succeed but the reality is that these studies did not bear out that hope," said Natalie Compagni-Portis, the lone patient representative on the panel.
The vote is not binding and FDA Commissioner Margaret Hamburg will make the final decision sometime after July 28. The drug is approved for multiple cancers and will still be available for breast cancer, though insurers are expected to drop coverage if it loses FDA approval.
The FDA began steps to remove Avastin's breast cancer approval in December, but Roche took the rare step of appealing that decision and lobbied the agency and Congress for a second hearing.
The dramatic, contentious tone of the two-day hearing underscored the difficulty of removing an option for cancer patients, even when backed by scientific evidence.
Immediately after the final vote, patients in the audience erupted in shouts against the FDA and its experts.
"What do you want us to take!? We have nothing else!" shouted Christi Turnage, of Madison, Miss. Turnage said her cancer has been undetectable for more than two years since starting therapy with Avastin.
A spokesman for the Abigail Alliance, which advocates for access to experimental medicine, said the vote should be overruled.
"This was a kangaroo court," said Steven Walker, the group's co-founder. "There wasn't one dissenting thought up there, let alone one dissenting vote."
Assuming the FDA follows through on the withdrawal, drugmaker Roche could lose up to $1 billion in revenue for its best-selling product, which generates over $6 billion per year. Avastin is FDA-approved for various types of colon, lung, kidney and brain cancer, which are not part of the debate. Doctors will still be allowed to prescribe Avastin for breast cancer, though insurers may not pay for it. When administration fees are included, a year's treatment of Avastin can cost $100,000.
Roche's Genentech unit argued the drug should remain available while it conducts more research on which patients benefit most from the injectable drug. The drug is approved for breast cancer that has spread, or metastasized, to other parts of the body. Such cancer is generally considered incurable.
"The data tell us it is better for women diagnosed with metastatic breast cancer to have Avastin as an approved treatment option," said Hal Barron, Roche executive vice president.
Wednesday's vote came after two days of hearings that often resembled a courtroom trial, complete with testimony, cross-examination and a final jury verdict. In a public comment period Tuesday, Avastin patients and their families took the role of witnesses against the FDA.
"Make no mistake, this hearing is a death trial, not of Avastin but of these women who rely on Avastin to stay alive," said Terry Kalley, whose wife takes Avastin for breast cancer.
Kalley formed a group called Freedom of Access to Medicines to protest and lobby the FDA. He says the group does not receive funding from Roche.
Panelists said Avastin's ability to slow tumor growth _ measured through medical imaging scans _ has not translated into meaningful benefit for breast cancer patients.
"I think as treating clinicians we have to ask ourselves: What are we doing in terms of helping patients? Simply delaying a change in a CT scan for a month or two is not significant unless it's accompanied by other improvements in how the patients are doing or overall survival improvement," said panelist Dr. Wyndam Wilson of the National Cancer Institute.
The FDA granted Avastin accelerated approval in 2008 based on one study in which it slowed growth of breast cancer tumors for more than five months when combined with chemotherapy.
But that delay shrunk to less than three months in follow-up studies when the drug was paired with other types of chemotherapy. Across all studies, patients taking Avastin did not live any longer and suffered side effects like infection, high blood pressure and blood clots.
Most cancer experts say the drug should remain available for patients who are already responding well, even if its approval is withdrawn.
"I think the FDA is doing the right thing since the drug has some serious complications," said Dr. Stephanie Bernik of Lenox Hill Hospital in New York. "However, there are definitely patients who are benefiting from the drug and if the FDA completely withdraws approval those patients may find it hard to get access."
One potential option to keep the drug available would be for Roche to pay for it when patients have no other option. The company already provides the drug for free to patients who meet certain financial criteria or don't have health coverage.
Roche has suggested that Avastin works differently depending on which chemotherapy drug it is paired with. The drugmaker essentially asked the FDA for time to repeat its initial study that had the strongest results, theorizing that Avastin works best with the chemotherapy paclitaxel. Such a study would not be completed before 2016.
But the FDA rejected that argument, saying there is no evidence Avastin interacts differently with various chemotherapies, and that continuing approval cannot be justified based on one study completed six years ago.
"No trial has shown that patients treated with Avastin lived longer than those not treated with Avastin," said FDA's director for new drugs, Dr. John Jenkins. "All clinical trials show an increase in serious adverse events."
The Avastin review will have broad repercussions for patients and the pharmaceutical industry.
Since the early 1990s the FDA has granted accelerated approval to dozens of drugs based on promising early results, on the condition that their effectiveness is confirmed in later studies. That policy has been praised by patients with HIV, cancer and other deadly diseases where access to experimental treatments can mean life or death.
But the flipside of the program means removing drugs from the market if their initial promise isn't confirmed by later studies. And until last year the agency had never removed a drug from the market because of incomplete or unconvincing follow-up data.
With the removal of that leukemia drug from Pfizer, and now the proceedings over Avastin, analysts say the FDA is poised to crack down on drugs whose effectiveness hasn't been confirmed in later studies.
Source: NC Times (June 2011)
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U.S. delays breast cancer ruling for Roche's Avastin
U.S. regulators have extended by three months a review of Roche Holding AG's blockbuster drug Avastin in breast cancer, the company said on Friday.
The Food and Drug Administration has made no decision on whether to revoke Avastin's approval for treating breast cancer patients as an advisory panel has recommended, the FDA and the company said.
Roche unit Genentech said it had submitted additional information to the FDA on two applications to expand Avastin's approved breast cancer uses to include combining the drug with other types of chemotherapy.
The new information prompted the FDA to extend the review of those uses until December 17, a Genentech statement said.
An FDA advisory panel that met in July urged the agency to reject those applications and to remove the drug's current approval for breast cancer. There is no set timeline for an FDA ruling on whether to revoke the breast cancer approval, Genentech spokeswoman Charlotte Arnold said.
Avastin won U.S. clearance for breast cancer in 2008 based on a study showing the drug stalled cancer growth by 5.5 months. The FDA required Roche to run follow-up studies to confirm the drug worked. Later studies found only a one- to three-month delay in breast cancer growth.
No studies showed Avastin extended the lives of patients with advanced breast cancer.
About $1 billion of Avastin's more than $6 billion in yearly sales come from breast cancer uses, analysts estimate. The product is Roche's top-selling drug, accounting for 13 percent of 2009 sales.
If the FDA pulls the breast cancer approval, the drug would remain on the market with clearance for colon, lung, brain and kidney cancers.
Doctors still could prescribe Avastin for breast cancer but sales likely would fall. Insurers may refuse to pay Avastin's $8,000-a-month pricetag for breast cancer patients without FDA approval.
Cancer patients and some advocacy groups have lobbied the FDA to keep the breast cancer approval, saying patients need options.
FDA spokeswoman Erica Jefferson said the agency "will be reviewing the additional data submitted by the company to make a science-based decision with the best interest of patients in mind."
SOURCE : Reuters 17.9.2010
LINK TO SOURCE
WARNINGS AND PRECAUTIONS
- Arterial Thromboembolic Events … Among patients receiving Avastin in combination with chemotherapy, the risk of developing ATE during therapy was increased in patients with a history of arterial thromboembolism, diabetes, or age greater than 65
- Proteinuria …In an exploratory, pooled analysis of 8,273 patients treated in 7 randomized clinical trials, 5.4% (271 of 5037) of patients receiving Avastin in combination with chemotherapy experienced Grade ≥ 2 proteinuria. The Grade ≥ 2 proteinuria resolved in 74.2% (201 of 271) of patients. Avastin was re-initiated in 41.7% (113 of 271) of patients. Of the 113 patients who re-initiated Avastin, 47.8% (54 of 113) experienced a second episode of Grade ≥ 2 proteinuria
Source : FDA (Dec 2013)
Researchers Detail Possible Resistance Mechanisms of Colorectal Cancer to Bevacizumab (Avastin)
A University of Colorado Cancer Center study published in the journal PLoS One shows that when colorectal cancer is targeted by the drug bevacizumab (Avastin), tumors may switch dependence from VEGF-A, which is targeted by the drug, to related growth factors in including VEGF-C, VEGF-D and placental growth factor. This change to new growth-factor dependence may allow colorectal cancer to push past bevacizumab’s blockage of VEGF-A to continue to drive tumor growth.“Think of it like damming a river. Bevacizumab can block the main flow, but then once a tumor’s need builds up behind this dam, water starts to flow around the blockage in the form of streams and tributaries. That’s like these other growth factors – eventually a tumor becomes able to use these tributaries of VEGF-C, VEGF-D and placental growth factor to supply itself with the ‘water’ it needs,” says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of Medical Oncology at the University of Colorado School of Medicine.
The analogy of liquid is an apt one – bevacizumab slows cancer’s growth by limiting a tumor’s ability to grow the new blood vessels it needs to supply itself with nutrients. Especially in combination with chemotherapy, bevacizumab has proved an effective treatment for colorectal cancer. But then there frequently comes a point at which bevacizumab stops working and the tumor restarts its growth. This study asked why.
Specifically, Lieu and colleagues serially tested the levels of other VEGF-related growth factors in 42 patients treated with bevacizumab and chemotherapy, at many points during the course of their treatment.
“What we saw is that levels of VEGF-C and placental growth factor went up just before tumors progressed and then stayed high during the periods of tumor growth. Interestingly, VEGF-D was only elevated during progression. But it seems that tumors may be using these growth factors as ways to create blood vessel growth in the absence of VEGF-A, blocked by bevacizumab,” Lieu says.
Then the researchers also took a snapshot of levels in 403 colorectal cancer patients, at one time during treatment. Because this group included patients who were and were not being treated with chemotherapy along with bevacizumab, they could show that the rise in VEGF levels was, in fact, due to bevacizumab and not to some interaction with the chemotherapy.
“It’s too early to say with certainty that VEGF-C, VEGF-D, and placental growth factor are the cause of colorectal cancer resistance to bevacizumab, but the correlation we saw in this study is compelling,” Lieu says.
Current studies are exploring the use of drugs that block more blood-vessel-growth-promoting factors than VEGF-A. For example, Lieu points to the example of aflibercept (Zaltrap), which was given FDA approval in August, 2013 for the treatment of metastatic colorectal cancer, along with the chemotherapy regimen known as FOLFIRI. The drug inhibits placental growth factor along with VEGF-A.
“It’s an attractive strategy, and also proof of concept that by targeting not only the primary mechanism of tumor growth but also one or more of these ‘workarounds,’ this drug or other future drugs could stall growth longer than blocking any one of these growth factors, individually,” Lieu says.
Lieu points out that in addition to targeting these additional growth factors, the fact that spikes in VEGF-C and placental growth factor presage tumor progression could give doctors and researchers a clue that bevacizumab has lost its efficacy. Though more work is needed, Lieu can imagine using spikes in VEGF-C or prenatal growth factor to recommend evaluating new treatment options.
Source : Newswise
Link to Source
More Bad News for Avastin in Breast Cancer
A randomized trial found bevacizumab (Avastin) failed to improve outcomes in combination with chemotherapy in early triple-negative breast cancer, adding to the string of failures for the drug.Invasive disease-free survival (DFS) and preliminary overall survival (OS) results showed no significant advantage to the addition of bevacizumab compared with adjuvant chemotherapy alone, David Cameron, MD, of Edinburgh University in Scotland, and colleagues reported in the BEATRICE trial.
But there was some good news: The researchers found outcomes were somewhat better than the literature would suggest for this group of patients not responsive to estrogen-, progesterone-, or HER2-targeted agents, with 83% to 84% without invasive cancer recurrence at 3 years.
"But in terms of improvement in outcomes, giving 1 year of bevacizumab isn't the answer," he said at a San Antonio Breast Cancer Symposium (SABCS) press conference.
The findings followed on the heels of negative results at the same meeting from the LEA trial suggesting no benefit to bevacizumab as an add-on to hormonal therapy in advanced breast cancer.
The drug lost its approval for use in breast cancer late last year, after studies required by the FDA as a condition of its fast-track indication in metastatic HER2-negative breast cancer failed to confirm even much of a progression-free survival advantage.
"It's getting to the point where it's going to be difficult to know the role of bevacizumab, if any, in breast cancer," commented C. Kent Osborne, MD, of Baylor College of Medicine in Houston, who moderated the SABCS press conference.
"If it's going to work, you would think it would work in this situation," he explained. "What we're dealing with at that stage are microscopic metastases that haven't developed a sufficient blood supply yet. If you can prevent that blood supply from forming, you might have a more dramatic effect than in already established tumor like in metastatic breast cancer."
Osborne called the BEATRICE results disappointing and suggested a limited role for the drug unless other ongoing studies show otherwise.
The trial included 2,591 women with centrally confirmed triple-negative invasive early breast cancer starting adjuvant chemotherapy with a taxane or anthracycline or both.
The women were randomized to four to eight cycles of the physicians' choice of those cytotoxics either alone or with the addition of 5 mg/kg per week bevacizumab, which was continued afterward for a total of 1 year of treatment.
For the primary endpoint, invasive DFS rates were 83.7% with bevacizumab compared with 82.7% in the control group, for a hazard ratio of 0.87 (P=0.181). Invasive DFS was selected as the primary endpoint, "just as a check to make sure we're not inducing cancers in other areas," Cameron explained.
Interim OS results, with only 59% of the planned number of events accrued, suggested a similar hazard ratio of 0.84 for bevacizumab compared with chemotherapy alone (P=0.232).
An adequately-powered comparison of survival is expected in about a year, Cameron noted, though he said the results at least clearly show no evidence of harm.
Toxicity followed the known profile of the drugs. The analysis paid particular attention to cardiovascular risks, which Cameron noted have been of particular concern with bevacizumab, similar to trastuzumab (Herceptin).
A prospectively-measured ejection fraction drop of at least 10% to fall under the entry criteria threshold of 50% was more common in the bevacizumab group. NYHA class III or IV heart failure occurred in 0.5% and 0.6% of patients, respectively, without any cases in the chemotherapy alone group.
But about 80% of clinically-significant heart failure cases recovered.
"Yes, there are changes in ejection fraction, there is a low rate of more severe heart failure, but this is not outside of what we would have expected with this drug," Cameron concluded
Source : MedPage Today via San Antonio Breast Cancer Symposium Cameron D, et al "Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer" SABCS 2012; Abstract S6-5.
Link to Source
VA puts cork in Avastin use for eye disease
VA hospitals won't be giving patients Avastin to treat an eye disease. In the latest development in the controversial use of Roche's cancer drug for wet age-related macular degeneration, the Department of Veteran Affairs, one of the largest healthcare providers in the U.S., has pulled the plug on the off-label use of the drug for the blindness-causing ailment.
The VA's decision comes amid pressure from members in Congress to get Medicare to back Avastin's use for the eye disease. The drug is just a fraction of the cost of Roche's approved medicine for the eye ailment, Lucentis, but cases of serious eye infections linked to the off-label use of Avastin have raised questions about whether the low-cost option is the best for patients. The VA is investigating the Avastin option for macular degeneration.
"The Department of Veterans Affairs (VA) has ceased ophthalmologic use of Avastin pending the results of an ongoing investigation and will advise its physicians to consider alternate therapies," the VA announced, as quoted by Reuters. "Once the investigation is complete, VA will reassess how Avastin and similar therapies may be made available for ophthalmologic use and will issue further guidance."
This was good news for Regeneron ($REGN). Shares the Tarrytown, NY-based developer, which is close to a potential approval for a rival drug for the eye disease called Eylea, jumped on news about the VA's decision yesterday and hit a 20-year high during afternoon trading. A panel of experts unanimously supported approval of Eylea this summer, and the FDA is expected to make its decision on the drug by November, Reuters reported.
Another issue facing Avastin is that compounding is required before doctors can use the cancer med to treat the eye disease. "The question is whether the VA is comfortable from this point onwards using an off-label product that needs to be compounded by the pharmacy," Yaron Werber, an analyst with Citigroup, told Bloomberg. The analyst added that new regulations for the compounding process could also affect the drug's off-label use.
Source : Fierce Pharma
Link to Source
More eye patients go blind after Avastin injections
There's another cluster of eye infections, some causing blindness, in patients using Avastin for macular degeneration. This time, the cases cropped up at a Veterans Affairs facility in Los Angeles; 5 people who were injected with Avastin lost vision in the treated eye.
The Genentech cancer drug isn't approved for use in the eye. But ophthalmologists have turned to it as a cheaper alternative to Genentech's Lucentis drug for wet age-related macular degeneration. It costs around $50 per injection, compared with $2,000 or so for the purpose-built drug.
The four LA infections join four at a VA hospital in Nashville and another cluster of 12 in the Miami area. As Reuters notes, Genentech--now owned by Roche--has for years argued that repackaging Avastin into doses small enough for eye use risked contamination. The company moved several years ago to restrict distribution to cut down on Avastin repackaging, but compounding pharmacies continue to prepare doses for ophthalmic use.
That could change, and given the big price difference, it could be a boon for Genentech, but a cost burden for Medicare, which saves big bucks thanks to this off-label Avastin use. The Los Angeles VA has already suspended use of Avastin for macular degeneration and is turning to Lucentis instead, the New York Times reports.
Source : Fierce Pharma
Link to Source
FDA panel: Revoke drug's breast cancer approval
A panel of cancer experts has ruled for a second time that Avastin, the best-selling cancer drug in the world, should no longer be used in breast cancer patients, clearing the way for the government to remove its endorsement from the drug.
The unprecedented vote Wednesday by the Food and Drug Administration advisory panel comes less than a year after the same panel reached the same conclusion.
The six members of the FDA oncology drug panel voted unanimously that Avastin is ineffective, unsafe and should have its approval for breast cancer withdrawn.
"I think we all wanted Avastin to succeed but the reality is that these studies did not bear out that hope," said Natalie Compagni-Portis, the lone patient representative on the panel.
The vote is not binding and FDA Commissioner Margaret Hamburg will make the final decision sometime after July 28. The drug is approved for multiple cancers and will still be available for breast cancer, though insurers are expected to drop coverage if it loses FDA approval.
The FDA began steps to remove Avastin's breast cancer approval in December, but Roche took the rare step of appealing that decision and lobbied the agency and Congress for a second hearing.
The dramatic, contentious tone of the two-day hearing underscored the difficulty of removing an option for cancer patients, even when backed by scientific evidence.
Immediately after the final vote, patients in the audience erupted in shouts against the FDA and its experts.
"What do you want us to take!? We have nothing else!" shouted Christi Turnage, of Madison, Miss. Turnage said her cancer has been undetectable for more than two years since starting therapy with Avastin.
A spokesman for the Abigail Alliance, which advocates for access to experimental medicine, said the vote should be overruled.
"This was a kangaroo court," said Steven Walker, the group's co-founder. "There wasn't one dissenting thought up there, let alone one dissenting vote."
Assuming the FDA follows through on the withdrawal, drugmaker Roche could lose up to $1 billion in revenue for its best-selling product, which generates over $6 billion per year. Avastin is FDA-approved for various types of colon, lung, kidney and brain cancer, which are not part of the debate. Doctors will still be allowed to prescribe Avastin for breast cancer, though insurers may not pay for it. When administration fees are included, a year's treatment of Avastin can cost $100,000.
Roche's Genentech unit argued the drug should remain available while it conducts more research on which patients benefit most from the injectable drug. The drug is approved for breast cancer that has spread, or metastasized, to other parts of the body. Such cancer is generally considered incurable.
"The data tell us it is better for women diagnosed with metastatic breast cancer to have Avastin as an approved treatment option," said Hal Barron, Roche executive vice president.
Wednesday's vote came after two days of hearings that often resembled a courtroom trial, complete with testimony, cross-examination and a final jury verdict. In a public comment period Tuesday, Avastin patients and their families took the role of witnesses against the FDA.
"Make no mistake, this hearing is a death trial, not of Avastin but of these women who rely on Avastin to stay alive," said Terry Kalley, whose wife takes Avastin for breast cancer.
Kalley formed a group called Freedom of Access to Medicines to protest and lobby the FDA. He says the group does not receive funding from Roche.
Panelists said Avastin's ability to slow tumor growth _ measured through medical imaging scans _ has not translated into meaningful benefit for breast cancer patients.
"I think as treating clinicians we have to ask ourselves: What are we doing in terms of helping patients? Simply delaying a change in a CT scan for a month or two is not significant unless it's accompanied by other improvements in how the patients are doing or overall survival improvement," said panelist Dr. Wyndam Wilson of the National Cancer Institute.
The FDA granted Avastin accelerated approval in 2008 based on one study in which it slowed growth of breast cancer tumors for more than five months when combined with chemotherapy.
But that delay shrunk to less than three months in follow-up studies when the drug was paired with other types of chemotherapy. Across all studies, patients taking Avastin did not live any longer and suffered side effects like infection, high blood pressure and blood clots.
Most cancer experts say the drug should remain available for patients who are already responding well, even if its approval is withdrawn.
"I think the FDA is doing the right thing since the drug has some serious complications," said Dr. Stephanie Bernik of Lenox Hill Hospital in New York. "However, there are definitely patients who are benefiting from the drug and if the FDA completely withdraws approval those patients may find it hard to get access."
One potential option to keep the drug available would be for Roche to pay for it when patients have no other option. The company already provides the drug for free to patients who meet certain financial criteria or don't have health coverage.
Roche has suggested that Avastin works differently depending on which chemotherapy drug it is paired with. The drugmaker essentially asked the FDA for time to repeat its initial study that had the strongest results, theorizing that Avastin works best with the chemotherapy paclitaxel. Such a study would not be completed before 2016.
But the FDA rejected that argument, saying there is no evidence Avastin interacts differently with various chemotherapies, and that continuing approval cannot be justified based on one study completed six years ago.
"No trial has shown that patients treated with Avastin lived longer than those not treated with Avastin," said FDA's director for new drugs, Dr. John Jenkins. "All clinical trials show an increase in serious adverse events."
The Avastin review will have broad repercussions for patients and the pharmaceutical industry.
Since the early 1990s the FDA has granted accelerated approval to dozens of drugs based on promising early results, on the condition that their effectiveness is confirmed in later studies. That policy has been praised by patients with HIV, cancer and other deadly diseases where access to experimental treatments can mean life or death.
But the flipside of the program means removing drugs from the market if their initial promise isn't confirmed by later studies. And until last year the agency had never removed a drug from the market because of incomplete or unconvincing follow-up data.
With the removal of that leukemia drug from Pfizer, and now the proceedings over Avastin, analysts say the FDA is poised to crack down on drugs whose effectiveness hasn't been confirmed in later studies.
Source: NC Times (June 2011)
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U.S. delays breast cancer ruling for Roche's Avastin
U.S. regulators have extended by three months a review of Roche Holding AG's blockbuster drug Avastin in breast cancer, the company said on Friday.
The Food and Drug Administration has made no decision on whether to revoke Avastin's approval for treating breast cancer patients as an advisory panel has recommended, the FDA and the company said.
Roche unit Genentech said it had submitted additional information to the FDA on two applications to expand Avastin's approved breast cancer uses to include combining the drug with other types of chemotherapy.
The new information prompted the FDA to extend the review of those uses until December 17, a Genentech statement said.
An FDA advisory panel that met in July urged the agency to reject those applications and to remove the drug's current approval for breast cancer. There is no set timeline for an FDA ruling on whether to revoke the breast cancer approval, Genentech spokeswoman Charlotte Arnold said.
Avastin won U.S. clearance for breast cancer in 2008 based on a study showing the drug stalled cancer growth by 5.5 months. The FDA required Roche to run follow-up studies to confirm the drug worked. Later studies found only a one- to three-month delay in breast cancer growth.
No studies showed Avastin extended the lives of patients with advanced breast cancer.
About $1 billion of Avastin's more than $6 billion in yearly sales come from breast cancer uses, analysts estimate. The product is Roche's top-selling drug, accounting for 13 percent of 2009 sales.
If the FDA pulls the breast cancer approval, the drug would remain on the market with clearance for colon, lung, brain and kidney cancers.
Doctors still could prescribe Avastin for breast cancer but sales likely would fall. Insurers may refuse to pay Avastin's $8,000-a-month pricetag for breast cancer patients without FDA approval.
Cancer patients and some advocacy groups have lobbied the FDA to keep the breast cancer approval, saying patients need options.
FDA spokeswoman Erica Jefferson said the agency "will be reviewing the additional data submitted by the company to make a science-based decision with the best interest of patients in mind."
SOURCE : Reuters 17.9.2010
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