SILVER SPRING, Md.—The U.S. Food and Drug Administration (FDA) has made life a bit more difficult for three Big Pharma players with rulings in regard to tanezumab and Avastin, but the ripples may be felt beyond merely the sting of potential wasted efforts and lost revenue, according to global analysis and opinion firm Datamonitor and other market watchers.
First came Pfizer's announcement earlier in the summer that it had suspended clinical trials of its pain drug tanezumab—at the request of the FDA—in patients with osteoarthritis after several patients taking the experimental drug experienced worsening of the osteoarthritis, leading to joint replacement.
More recent was the issuance of an FDA advisory committee's suggestion to revoke the approval of Avastin, from Roche and Genentech, for treating breast cancer, with the committee voting 12-1 in late July after new studies presented to the panel showed more side effects among women being treated with Avastin and no overall survival benefit, though they did show women taking the drug had an extra month to 2.9 months of progression-free survival. In this decision, it is not clear whether the FDA will rule according to the committee's advice—though it typically does—but even so the drug still should be marketable for treating colon, lung and other cancers.
Long-term with tanezumab
Looking at the Pfizer blow, Simon King, a healthcare analyst at Datamonitor, calls the FDA decision a "worrying development for Pfizer" in part because after having acquired rival company Wyeth in late 2009, Pfizer's research and development spending is projected to reach $9.9 billion in 2010 compared to a Big Pharma average of $6.3 billion, based on Datamonitor forecasts.
With this in mind, King says, the decision is potentially a big problem for Pfizer after having "faced an accumulation of negative news flow regarding its pipeline over the last 18 months. This follows the recent confirmation that the acute myeloid leukemia therapy Mylotarg is to be withdrawn from the U.S. market," he notes.
"While difficulties associated with successful R&D-to-market transition are clear and such setbacks remain common place across the industry landscape, Pfizer remains in a period of notable portfolio transition," King adds. "It desperately requires the translation of R&D investment into revenues if it is to offset losses associated with expiry-exposed products such as Lipitor which will lose patent exclusivity in 2011."
Latest Datamonitor forecasts suggest that just 10 percent of Pfizer's 2015 sales will be derived from new launches, suggesting that the company will continue to face competitive threats associated with a mature product offering.
On the "glass half full" side of the issue for Pfizer, severe reactions to tanezumab have not been observed in non-osteoarthritis patient populations taking tanezumab, according to Pfizer.
A Daily Finance article notes that "Several in the media recently questioned the reason Pfizer stock has remained so depressed and out of favor with Wall Street. Certainly, Pfizer is about to lose patent protection on its biggest selling drug—the cholesterol treatment Lipitor—and has yet to come up with other drugs that would replace revenue lost to generic competition. Yet some felt that fundamentally the company is worth more than its current price levels. But this recent development perhaps puts more weight in Pfizer's bear camp."
According to EP Vantage, the future of tanezumab may not all that hangs in the balance, and the FDA decision may have a ripple effect that could extend to other companies with anti-NGF candidate antibodies under development.
"While relatively few are in the pipeline, a who's who of Big Pharma are potentially implicated by the outcome of these analyses," EP Vantage reports. "The outcome of the FDA and Pfizer's review of the adverse event data is therefore a pivotal step in the overall development of this class of antibody. Should the effect be drug-specific, the death knell for tanezumab predicted by some analysts could be music to the ears of sanofi-aventis and Regeneron. However, should a class effect emerge, the other players will have some awkward development decisions to take."
Avast ye! Avastin
The most immediate effect of the FDA advisory panel ruling—should FDA follow the advice—for Avastin is that it will present a setback for Roche and Genentech in terms of growth opportunities for Avastin, according to Rashmi Wadehra, a healthcare analyst at Datamonitor.
But in addition, "Breast cancer incidence continues to rise in women with an estimated 500,000 cases reported annually in the seven major markets. Current treatment options are restricted to patients with HER2 positive metastatic breast cancer rather than HER2 negative patients that are fairly underserved. The FDA's decision will therefore have a significant bearing on the overall commercial success of Avastin, although continued success in CRC and NSCLC should allow it to retain its leading position in the oncology market with company-reported sales of $5.7 billion in 2009."
Wadehra points out that the panel ruling doesn't necessarily mean that the FDA will follow the recommendation.
"The FDA has gone against the advisory committee in the past, most notably when recommending Tarceva in the maintenance therapy of non small cell lung cancer in spite of 12-1 ruling against it," Wadehra notes. "Indeed, this was also the case when the FDA granted accelerated approval for Avastin in breast cancer in 2008. At the time, the FDA advisory panel voted 5-4 against approving the drug for breast cancer. The FDA went against its recommendation and granted accelerated approval."
However, "even if the FDA follows a similar approach with Avastin—allowing its use in breast cancer—the drug's uptake is likely to be limited based on current clinical data," Wadehra notes.
On the more inflammatory end of the analysis would be Republican Sen. David Vitter of Louisiana, who calls the FDA panel decision "essentially government rationing."
"I shudder at the thought of a government panel assigning a value to a day of a person's life," Vitter said in a statement. "It is sickening to think that care would be withheld from a patient simply because their life is not deemed valuable enough." In a letter to the FDA cancer division leader, Richard Pazdur, Vitter said the committee's vote appeared to be based on cost effectiveness, not safety issues.
"I am not suggesting that Avastin is a perfect drug, but it has a proven record of effective treatment for some patients when used along with chemotherapy," he wrote. Of course, it should be noted that Vitter's mother-in-law died of breast cancer, and he also has spoken out against new U.S. Preventive Services Task Force mammogram guidelines that said yearly tests shouldn't be automatic for most women under 50.
A New York Times editorial says the recent "flameout" of the breast cancer drug Avastin "will pose a critical test" on whether FDA will "have the courage to reverse course when a medical treatment that it approved based on preliminary evidence flops badly in follow-up studies."
As the Times editorial notes, a single clinical trial showed that when used with another drug, Avastin could slow breast cancer's progression but "did not significantly extend patients' lives … Now two follow-up trials by the manufacturer have failed to confirm even those meager gains."
As such, the Times sees the panel ruling as very sensible, but notes that FDA "has rarely removed drugs that were given accelerated approval and sometimes has failed even to compel completion of follow-up studies."
First came Pfizer's announcement earlier in the summer that it had suspended clinical trials of its pain drug tanezumab—at the request of the FDA—in patients with osteoarthritis after several patients taking the experimental drug experienced worsening of the osteoarthritis, leading to joint replacement.
More recent was the issuance of an FDA advisory committee's suggestion to revoke the approval of Avastin, from Roche and Genentech, for treating breast cancer, with the committee voting 12-1 in late July after new studies presented to the panel showed more side effects among women being treated with Avastin and no overall survival benefit, though they did show women taking the drug had an extra month to 2.9 months of progression-free survival. In this decision, it is not clear whether the FDA will rule according to the committee's advice—though it typically does—but even so the drug still should be marketable for treating colon, lung and other cancers.
Long-term with tanezumab
Looking at the Pfizer blow, Simon King, a healthcare analyst at Datamonitor, calls the FDA decision a "worrying development for Pfizer" in part because after having acquired rival company Wyeth in late 2009, Pfizer's research and development spending is projected to reach $9.9 billion in 2010 compared to a Big Pharma average of $6.3 billion, based on Datamonitor forecasts.
With this in mind, King says, the decision is potentially a big problem for Pfizer after having "faced an accumulation of negative news flow regarding its pipeline over the last 18 months. This follows the recent confirmation that the acute myeloid leukemia therapy Mylotarg is to be withdrawn from the U.S. market," he notes.
"While difficulties associated with successful R&D-to-market transition are clear and such setbacks remain common place across the industry landscape, Pfizer remains in a period of notable portfolio transition," King adds. "It desperately requires the translation of R&D investment into revenues if it is to offset losses associated with expiry-exposed products such as Lipitor which will lose patent exclusivity in 2011."
Latest Datamonitor forecasts suggest that just 10 percent of Pfizer's 2015 sales will be derived from new launches, suggesting that the company will continue to face competitive threats associated with a mature product offering.
On the "glass half full" side of the issue for Pfizer, severe reactions to tanezumab have not been observed in non-osteoarthritis patient populations taking tanezumab, according to Pfizer.
A Daily Finance article notes that "Several in the media recently questioned the reason Pfizer stock has remained so depressed and out of favor with Wall Street. Certainly, Pfizer is about to lose patent protection on its biggest selling drug—the cholesterol treatment Lipitor—and has yet to come up with other drugs that would replace revenue lost to generic competition. Yet some felt that fundamentally the company is worth more than its current price levels. But this recent development perhaps puts more weight in Pfizer's bear camp."
According to EP Vantage, the future of tanezumab may not all that hangs in the balance, and the FDA decision may have a ripple effect that could extend to other companies with anti-NGF candidate antibodies under development.
"While relatively few are in the pipeline, a who's who of Big Pharma are potentially implicated by the outcome of these analyses," EP Vantage reports. "The outcome of the FDA and Pfizer's review of the adverse event data is therefore a pivotal step in the overall development of this class of antibody. Should the effect be drug-specific, the death knell for tanezumab predicted by some analysts could be music to the ears of sanofi-aventis and Regeneron. However, should a class effect emerge, the other players will have some awkward development decisions to take."
Avast ye! Avastin
The most immediate effect of the FDA advisory panel ruling—should FDA follow the advice—for Avastin is that it will present a setback for Roche and Genentech in terms of growth opportunities for Avastin, according to Rashmi Wadehra, a healthcare analyst at Datamonitor.
But in addition, "Breast cancer incidence continues to rise in women with an estimated 500,000 cases reported annually in the seven major markets. Current treatment options are restricted to patients with HER2 positive metastatic breast cancer rather than HER2 negative patients that are fairly underserved. The FDA's decision will therefore have a significant bearing on the overall commercial success of Avastin, although continued success in CRC and NSCLC should allow it to retain its leading position in the oncology market with company-reported sales of $5.7 billion in 2009."
Wadehra points out that the panel ruling doesn't necessarily mean that the FDA will follow the recommendation.
"The FDA has gone against the advisory committee in the past, most notably when recommending Tarceva in the maintenance therapy of non small cell lung cancer in spite of 12-1 ruling against it," Wadehra notes. "Indeed, this was also the case when the FDA granted accelerated approval for Avastin in breast cancer in 2008. At the time, the FDA advisory panel voted 5-4 against approving the drug for breast cancer. The FDA went against its recommendation and granted accelerated approval."
However, "even if the FDA follows a similar approach with Avastin—allowing its use in breast cancer—the drug's uptake is likely to be limited based on current clinical data," Wadehra notes.
On the more inflammatory end of the analysis would be Republican Sen. David Vitter of Louisiana, who calls the FDA panel decision "essentially government rationing."
"I shudder at the thought of a government panel assigning a value to a day of a person's life," Vitter said in a statement. "It is sickening to think that care would be withheld from a patient simply because their life is not deemed valuable enough." In a letter to the FDA cancer division leader, Richard Pazdur, Vitter said the committee's vote appeared to be based on cost effectiveness, not safety issues.
"I am not suggesting that Avastin is a perfect drug, but it has a proven record of effective treatment for some patients when used along with chemotherapy," he wrote. Of course, it should be noted that Vitter's mother-in-law died of breast cancer, and he also has spoken out against new U.S. Preventive Services Task Force mammogram guidelines that said yearly tests shouldn't be automatic for most women under 50.
A New York Times editorial says the recent "flameout" of the breast cancer drug Avastin "will pose a critical test" on whether FDA will "have the courage to reverse course when a medical treatment that it approved based on preliminary evidence flops badly in follow-up studies."
As the Times editorial notes, a single clinical trial showed that when used with another drug, Avastin could slow breast cancer's progression but "did not significantly extend patients' lives … Now two follow-up trials by the manufacturer have failed to confirm even those meager gains."
As such, the Times sees the panel ruling as very sensible, but notes that FDA "has rarely removed drugs that were given accelerated approval and sometimes has failed even to compel completion of follow-up studies."
