Dear ASPS Community Friends,
The following March 20th Reuters news report provides important and relevant information regarding FDA's recommendations for Pazopanib (Votrient) and Ariad (Taltorvic) which are two drugs that have been in Clinical Trial for soft tissue sarcoma.:
WASHINGTON | Tue Mar 20, 2012 4:59pm EDT
WASHINGTON (Reuters) - A U.S. Food and Drug Administration advisory panel recommended GlaxoSmithKline Plc's Votrient for soft-tissue sarcoma on Tuesday, but did not recommend a treatment for the same malady developed jointly by Merck & Co Inc and Ariad Pharmaceuticals Inc.
The FDA committee of outside experts voted 11-2 in finding that Votrient's ability to improve short-term survival without worsening symptoms in patients who receive chemotherapy outweighed adverse risks and a lack of evidence that it can extend overall survival.
The same panel voted 13-1 not to recommend Merck's drug Taltorvic for soft-tissue and bone sarcoma after reviewing data that associated the drug with serious adverse effects but produced only small improvements in patients who had completed at least four cycles of chemotherapy.
The regulatory agency will now consider the committee's recommendations in reaching separate decisions on whether each drug should be approved for sale in the United States for soft-tissue sarcoma.
An FDA official said the agency could give Votrient accelerated approval to ensure further study of the drug's efficacy, including questions about patient quality of life, on patients with soft-tissue sarcoma. The drug is already approved for renal cell carcinoma.
Shares of GlaxoSmithKline closed 0.2 percent higher at 1433.5 pence in London trading after the panel made its recommendation for Votrient.
The committee's vote on Taltorvic occurred as share trading closed in New York, with Merck down 13 cents at $37.76 and Ariad shares off 18 cents at $15.05.
Soft-tissue sarcoma is a rare but aggressive form of cancer that afflicted about 11,000 Americans last year, 4,000 of whom died from the disease, according to the National Cancer Institute.
FDA committee members said they were willing to consider treatments shown in clinical trials to be only marginally effective because the disease is so aggressive and alternative treatments so few.
That was part of the rationale behind the panel's recommendation for Glaxo's Votrient, which was shown to allow patients to survive three months longer on average, without disease progression, compared with subjects who received a placebo, but showed no significant improvement in overall survival rates.
Committee members were less charitable toward Taltorvic, which is also known by the chemical name ridoforolimus, which was shown to improve survival without disease progression by only a matter of weeks but with adverse impacts including death and hospitalization.
Panelists noted findings that four out of five patients who participated in the Taltorvic study experienced adverse effects severe enough for the treatment to be scaled back or discontinued.
"How is it clinically meaningful to expose patients, for far longer than they should need to be, to a toxic drug for the benefit of three weeks?" asked the panel's chairman, Dr. Wyndham Wilson of the National Cancer Institute.
Adverse events from Talrovic included pneumonitis, renal failure, pneumonia and other infections as well as hyperglycemia.
Matthew Alsante, executive director of the Sarcoma Foundation of America, implored panel members to approve both drugs, saying sarcoma patients have few alternative treatments for fending off worsening symptoms and death.
(Reporting by David Morgan; Editing by Gary Hill)
With special caring thoughts and continued Hope,
Bonni
FDA recommendations for the drugs Pazopanib & Ariad
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Bonni Hess
- Senior Member
- Posts: 1677
- Joined: Mon Aug 14, 2006 11:32 pm
- Location: Sammamish, WA USA
Re: FDA recommendations for the drugs Pazopanib & Ariad
FDA Panel Backs Pazopanib for Sarcoma
BY ELIZABEtH MECHCATIE | 2012-03-20
SILVER SPRING, MARYLAND (EGMN) – A U.S. Food and Drug Administration advisory panel supports approval of the angiogenesis inhibitor pazopanib as a treatment for advanced soft-tissue sarcoma, despite some concerns about the degree of response in the main study considered for approval.
At its March 20 meeting, the Oncologic Drugs Advisory Committee (ODAC) voted 11-2 that pazopanib(Votrient) has a favorable risk-benefit profile as a treatment for advanced soft-tissue sarcoma (STS) in patients who have received prior chemotherapy, the new indication proposed by the manufacturer, GlaxoSmithKline.
In the pivotal placebo-controlled PALETTE study, the gain in median progression-free survival was 3 months, which was significant. The difference in median overall survival, a secondary end point, was 1.9 months, however, and this was not statistically significant.
Although panelists agreed that the effects of the drug were marginal, those voting in favor of approval said that they believed the effect was real. They reasoned that a 3-month benefit was meaningful to patients, as there are few options available for this rare tumor.
Several were encouraged by the fact that 14% of patients in the study remained still on treatment after 1 year (compared with 1% of those on placebo). Panelists also said that having a noncytotoxic treatment option for soft-tissue sarcomas would be beneficial.
Pazopanib, a tyrosine kinase inhibitor, targets the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and stem cell growth factor. It was approved in 2009 for the treatment of advanced renal cell carcinoma.
In the double-blind, phase III study, patients with soft-tissue sarcoma who had progressed during or following prior chemotherapy (including anthracyclines) were randomized to pazopanib, 800 mg daily, in tablet formulation (246 patients) or placebo (123 patients). They were examined every 4 weeks during a 12-week period and then every 8 weeks until evidence of progression, death, excessive toxicity, or patient withdrawal.
A little more than half the patients were female, their median age was 51-56 years; most were from the European Union, 12% were from the United States. The most common histologies were leiomyosarcoma (40% on placebo and 44% on pazopanib) and synovial sarcoma (11% and 10%, respectively).
Median progression-free survival, the primary end point, reached 4.6 months among those on pazopanib, compared with 1.6 months among those on placebo, a statistically significant difference that represented a 65% reduced risk.
Treatment was not associated with a statistically significant improvement in overall survival, however. It reached 12.6 months among those on pazopanib and 10.7 months among those on placebo, for a reduced risk of 13%.
With a few exceptions, the safety profile in sarcoma trials was similar to the safety profile of patients in renal cell carcinoma studies, with adverse effects that included hepatoxicity, hypothyroidism, and hemorrhagic events.
“From my own experience of treating many sarcoma patients, this is a drug I would like to have in my armamentarium,” panelist Dr. Lee J. Helman, scientific director for clinical research, at the Center for Cancer Research at the U.S. National Cancer Institute, Bethesda, Maryland.
While he would have liked to see a greater impact on progression-free survival, he said, “It’s a little step ... but it’s a little step in a field that has had nothing.”
The company has proposed that the indication include the statement “Important limitations of use: The phase [III] STS trial population excluded patients with adipocytic STS or gastrointestinal stromal tumors.”
The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting.
Occasionally, a panelist may be given a waiver and at this meeting, Dr. Deborah K. Armstrong was granted a waiver to participate in the meeting, because of her expertise in STS. The conflict pertained to study grants received by her employer, the Sidney Kimmel Comprehensive Cancer Center in Philadelphia, according to the FDA.
BY ELIZABEtH MECHCATIE | 2012-03-20
SILVER SPRING, MARYLAND (EGMN) – A U.S. Food and Drug Administration advisory panel supports approval of the angiogenesis inhibitor pazopanib as a treatment for advanced soft-tissue sarcoma, despite some concerns about the degree of response in the main study considered for approval.
At its March 20 meeting, the Oncologic Drugs Advisory Committee (ODAC) voted 11-2 that pazopanib(Votrient) has a favorable risk-benefit profile as a treatment for advanced soft-tissue sarcoma (STS) in patients who have received prior chemotherapy, the new indication proposed by the manufacturer, GlaxoSmithKline.
In the pivotal placebo-controlled PALETTE study, the gain in median progression-free survival was 3 months, which was significant. The difference in median overall survival, a secondary end point, was 1.9 months, however, and this was not statistically significant.
Although panelists agreed that the effects of the drug were marginal, those voting in favor of approval said that they believed the effect was real. They reasoned that a 3-month benefit was meaningful to patients, as there are few options available for this rare tumor.
Several were encouraged by the fact that 14% of patients in the study remained still on treatment after 1 year (compared with 1% of those on placebo). Panelists also said that having a noncytotoxic treatment option for soft-tissue sarcomas would be beneficial.
Pazopanib, a tyrosine kinase inhibitor, targets the vascular endothelial growth factor receptor, the platelet-derived growth factor receptor, and stem cell growth factor. It was approved in 2009 for the treatment of advanced renal cell carcinoma.
In the double-blind, phase III study, patients with soft-tissue sarcoma who had progressed during or following prior chemotherapy (including anthracyclines) were randomized to pazopanib, 800 mg daily, in tablet formulation (246 patients) or placebo (123 patients). They were examined every 4 weeks during a 12-week period and then every 8 weeks until evidence of progression, death, excessive toxicity, or patient withdrawal.
A little more than half the patients were female, their median age was 51-56 years; most were from the European Union, 12% were from the United States. The most common histologies were leiomyosarcoma (40% on placebo and 44% on pazopanib) and synovial sarcoma (11% and 10%, respectively).
Median progression-free survival, the primary end point, reached 4.6 months among those on pazopanib, compared with 1.6 months among those on placebo, a statistically significant difference that represented a 65% reduced risk.
Treatment was not associated with a statistically significant improvement in overall survival, however. It reached 12.6 months among those on pazopanib and 10.7 months among those on placebo, for a reduced risk of 13%.
With a few exceptions, the safety profile in sarcoma trials was similar to the safety profile of patients in renal cell carcinoma studies, with adverse effects that included hepatoxicity, hypothyroidism, and hemorrhagic events.
“From my own experience of treating many sarcoma patients, this is a drug I would like to have in my armamentarium,” panelist Dr. Lee J. Helman, scientific director for clinical research, at the Center for Cancer Research at the U.S. National Cancer Institute, Bethesda, Maryland.
While he would have liked to see a greater impact on progression-free survival, he said, “It’s a little step ... but it’s a little step in a field that has had nothing.”
The company has proposed that the indication include the statement “Important limitations of use: The phase [III] STS trial population excluded patients with adipocytic STS or gastrointestinal stromal tumors.”
The FDA usually follows the recommendations of its advisory panels. Panelists have been cleared of potential conflicts of interest related to the topic of the meeting.
Occasionally, a panelist may be given a waiver and at this meeting, Dr. Deborah K. Armstrong was granted a waiver to participate in the meeting, because of her expertise in STS. The conflict pertained to study grants received by her employer, the Sidney Kimmel Comprehensive Cancer Center in Philadelphia, according to the FDA.
-
Bonni Hess
- Senior Member
- Posts: 1677
- Joined: Mon Aug 14, 2006 11:32 pm
- Location: Sammamish, WA USA
Re: FDA recommendations for the drugs Pazopanib & Ariad
Thank you for sharing the additional information Feng Zhou. I have also found another very recent article with similar, but additional information which I am posting here. It is very disappointing to read that the overall survival benefits of Pazopanib was only about two months, and that progression free survival for the patients in the study was only about three months, but it is unclear from this article whether any ASPS patients were involved in the study. As we know, each type of sarcoma is different and responds differently to different treatments, so my great Hope is that perhaps Pazopanib will prove to be significantly more successful for ASPS patients than it was for the patients in this study. Hopefully those ASPS patients who are currently taking Pazopanib and/or participating in a Pazopanib Clinical Trial will post and share their information on this Discussion Board in the Pazopanib topic so that we can all follow their treatment experience and results and all learn from each other with continued shared research and anecdotal experience information.
With special caring thoughts and continued Hope,
Bonni
The following is the related article:
GlaxoSmithKline: Masters of Innovation and Investment
Published Thu, Mar 22nd, 2012 Martin Denholm
3 Score one for innovation!
And emphatically, too.
By an 11 to 2 margin, the Food & Drug Administration’s Oncologic Drugs Advisory Committee just voted to pre-approve GlaxoSmithKline’s (NYSE: GSK) new cancer drug, Votrient.
At the same time, the panel unanimously rejected a similar drug by rival, Merck (NYSE: MRK) by 13 to 1.
Votrient treats patients with advanced soft-tissue sarcoma – a cancer that originates in bones, muscles, or tissues – and who’ve already undergone chemotherapy for the disease. These patients typically only survive about 12 to 18 months, according to the Associated Press.
It’s a somewhat niche area of medicine, too, because as Glaxo’s Senior Vice President of Oncology, Rafael Amado, states in the Philadelphia Business Journal:
“Treatment options for patients with advanced soft-tissue sarcoma are limited.”
This, despite the fact that the disease has a high fatality rate. The National Cancer Institute says there were 11,000 new diagnoses of soft-tissue sarcoma in 2011, resulting in 3,900 deaths.
And you can see why the panel pre-approved Votrient and rejected Merck’s offering…
What’s Three Months Worth to You?
Neither Votrient nor Merck’s drug, ridaforolimus, are intended to extend a patient’s life.
Well, not directly anyway.
Instead, they aim to improve “progression-free survival.” That is, slowing the rate at which the cancer regrows.
But the difference in success between Votrient and ridaforolimus was significant.
Studies showed that Votrient’s progression-free survival was 4.6 months, compared to just 1.6 months for the placebo – a three-month improvement.
By contrast, ridaforolimus only managed to extend the progression-free survival rate by a measly three weeks – from 14.6 weeks to 17.7 weeks. In addition, 60% of patients suffered side effects, which ranged from kidney damage, lung problems, high blood pressure and infection.
Hardly worth the risk, really. And 14% of patients agreed, electing to drop out of the study completely.
While Votrient also showed side effects, the panel said the “risk benefit assessment” swung more positively towards the drug, given that its progression-free survival improvement was much greater and because the drug also attacks another protein that causes cancerous tumors to grow, according to The Wall Street Journal.
As Dr. Mikkael Sekeres, of the Cleveland Clinic, told the Associated Press:
“There are no drugs approved by the FDA specifically for this indication and that’s what drove my decision to vote yes.”
So with Votrient already approved for kidney cancer and now pre-approval granted for soft-tissue sarcoma, it’s the first successful step for Glaxo’s strong drug pipeline this year. Typically, the FDA usually rubber stamps full approval to drugs that its advisory panels have previously recommended. The scheduled approval date is May 6.
With special caring thoughts and continued Hope,
Bonni
The following is the related article:
GlaxoSmithKline: Masters of Innovation and Investment
Published Thu, Mar 22nd, 2012 Martin Denholm
3 Score one for innovation!
And emphatically, too.
By an 11 to 2 margin, the Food & Drug Administration’s Oncologic Drugs Advisory Committee just voted to pre-approve GlaxoSmithKline’s (NYSE: GSK) new cancer drug, Votrient.
At the same time, the panel unanimously rejected a similar drug by rival, Merck (NYSE: MRK) by 13 to 1.
Votrient treats patients with advanced soft-tissue sarcoma – a cancer that originates in bones, muscles, or tissues – and who’ve already undergone chemotherapy for the disease. These patients typically only survive about 12 to 18 months, according to the Associated Press.
It’s a somewhat niche area of medicine, too, because as Glaxo’s Senior Vice President of Oncology, Rafael Amado, states in the Philadelphia Business Journal:
“Treatment options for patients with advanced soft-tissue sarcoma are limited.”
This, despite the fact that the disease has a high fatality rate. The National Cancer Institute says there were 11,000 new diagnoses of soft-tissue sarcoma in 2011, resulting in 3,900 deaths.
And you can see why the panel pre-approved Votrient and rejected Merck’s offering…
What’s Three Months Worth to You?
Neither Votrient nor Merck’s drug, ridaforolimus, are intended to extend a patient’s life.
Well, not directly anyway.
Instead, they aim to improve “progression-free survival.” That is, slowing the rate at which the cancer regrows.
But the difference in success between Votrient and ridaforolimus was significant.
Studies showed that Votrient’s progression-free survival was 4.6 months, compared to just 1.6 months for the placebo – a three-month improvement.
By contrast, ridaforolimus only managed to extend the progression-free survival rate by a measly three weeks – from 14.6 weeks to 17.7 weeks. In addition, 60% of patients suffered side effects, which ranged from kidney damage, lung problems, high blood pressure and infection.
Hardly worth the risk, really. And 14% of patients agreed, electing to drop out of the study completely.
While Votrient also showed side effects, the panel said the “risk benefit assessment” swung more positively towards the drug, given that its progression-free survival improvement was much greater and because the drug also attacks another protein that causes cancerous tumors to grow, according to The Wall Street Journal.
As Dr. Mikkael Sekeres, of the Cleveland Clinic, told the Associated Press:
“There are no drugs approved by the FDA specifically for this indication and that’s what drove my decision to vote yes.”
So with Votrient already approved for kidney cancer and now pre-approval granted for soft-tissue sarcoma, it’s the first successful step for Glaxo’s strong drug pipeline this year. Typically, the FDA usually rubber stamps full approval to drugs that its advisory panels have previously recommended. The scheduled approval date is May 6.
Re: FDA recommendations for the drugs Pazopanib & Ariad
Yes，“FDA committee members said they were willing to consider treatments shown in clinical trials to be only marginally effective because the disease is so aggressive and alternative treatments so few.”
According to a Nature review report,Pazopanib on synovial sarcoma with high efficiency.
The most disappointing is not to recommend Merck's drug Taltorvic (AP23573,ridoforolimus）! On Aug. 18,2005, the FDA approved orphan drug and fast-track status for a non-prodrug rapamycin analog (AP23573 injection, made by ARIAD Pharmaceuticals, Inc.) for the treatment of soft-tissue and bone sarcomas.
According to a Nature review report,Pazopanib on synovial sarcoma with high efficiency.
The most disappointing is not to recommend Merck's drug Taltorvic (AP23573,ridoforolimus）! On Aug. 18,2005, the FDA approved orphan drug and fast-track status for a non-prodrug rapamycin analog (AP23573 injection, made by ARIAD Pharmaceuticals, Inc.) for the treatment of soft-tissue and bone sarcomas.