& stung by its own Advisory Committee--Natrecor should be strict

[Guest guest]

& stung by its own Advisory Committee--Natrecor

should be strictly limited

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

Promoting Openness, Full Disclosure, and Accountability

http://www.ahrp.org

FYI

Kudos go to Dr. Eugene Braunwald and the 10 members of the advisory

committee that he heads.

Contrary to & expectations, the committee recommended

extensive warnings to physicians against prescribing Natrecor to

outpatients.

When physicians begin to exercise honest professional judgement--

without regard for financial considerations--only then can trust be

restored to medicine!

Contact: Vera Hassner Sharav

212-595-8974

veracare@...

THE NEW YORK TIMES

August 9, 2005

Expert Panel Gives Advice That Surprises a Drug Maker

By STEPHANIE SAUL

Call it the advisory committee that keeps on giving advice.

After two medical studies questioned the safety of its popular heart

failure therapy Natrecor, the Scios unit of & turned

in April to a technique government and business often use to make

problems go away: it formed an outside advisory committee.

The company appeared to be taken aback in June, though, when it

learned just how fiercely independent its committee, led by Dr.

Eugene Braunwald of Harvard Medical School, turned out to be.

Rather than the milquetoast findings often returned by such advisory

panels, Dr. Braunwald's committee of 10 medical experts determined

that use of Natrecor, an expensive intravenous therapy, should be

strictly limited to acutely ill patients in hospitals. The committee

asked Scios to begin warning doctors against the drug's use in

outpatients, a treatment that had not been approved by the Food and

Drug Administration but that had helped turn Natrecor into a big

money maker.

The committee did not stop there. Over the last two months, some

members have expressed concern about the ways Scios has responded to

its recommendations. To register the committee's dissatisfaction, Dr.

Braunwald has sent Scios several letters and has gone so far as to

ask for changes in company-sponsored medical education presentations

about Natrecor, several members said.

" I think that, not surprisingly, the panel was concerned that the

recommendations be taken seriously, " said one member, Dr. C.

Burnett of the Mayo Clinic College of Medicine, who added that Dr.

Braunwald had recently told the committee that Scios was heeding its

concerns.

Dr. Braunwald, a renowned heart-failure specialist, did not respond

to several requests for an interview. Scios defended its response to

the Braunwald committee's recommendations and said it was preparing

to expand its physician outreach campaign warning doctors against

using Natrecor in outpatients.

The company also said that, as of July 29, it had revised a toll-free

telephone line that had coached doctors and their staffs on how to

file insurance claims for outpatient Natrecor infusions. Now, the

line warns against such use.

The original phone line helped spur accusations from several leading

cardiologists that Scios was promoting Natrecor for an unapproved

use. They sounded alarms after concluding that Natrecor might raise

the likelihood of potentially fatal kidney problems and questioning

whether the drug was worth its high cost - about $500 per infusion.

Although doctors can administer drugs to patients as they see fit, a

company's promotion of drugs for unapproved, or off-label, use is

illegal. Scios's Natrecor marketing program, and whether it actively

promoted an off-label use of the drug, is now the target of a Justice

Department investigation in Boston.

Financial analysts viewed Natrecor as a potential blockbuster when it

arrived on the market in 2001. But after the drug reached $400

million in sales last year, its sales are off 20 percent this year,

the company has said. The primary benefit of Natrecor, a manufactured

version of a naturally occurring cardiac hormone, is that it

temporarily makes breathing easier for a heart-failure patient.

Some committee members said that their concerns about Scios's

handling of their recommendations began soon after the panel reported

its findings to the company on June 13. The report's crucial finding

was unambiguous: Natrecor should not be used in outpatients.

But rather than simply disseminate the report, Scios created its own

prefacing news release. The committee's conclusion that Natrecor

should not be used in outpatient settings was not clearly stated

until the final page of the five-page company document. Instead, the

news release played up the panel's recommendation that Scios gather

further data by continuing with a clinical trial, called Fusion II,

to determine the drug's usefulness in outpatients.

" The press release emphasized a small aspect of our recommendations -

that clinical trials should continue; it de-emphasized or made little

mention of the more important take-home points of our

recommendations, " said Dr. Milton Packer, a cardiologist at the

University of Texas Southwestern Medical Center in Dallas who served

on the committee.

Dr. Packer also said that the committee members were shocked several

weeks later when they received invitations as part of a mass mailing

to enroll in a continuing medical education program, financed by

Scios, that seemed to promote the outpatient use of Natrecor, whose

chemical name is nesiritide.

" We were flabbergasted. " Dr. Packer said. " Scios was sponsoring

meetings to discuss nesiritide and its potential use in outpatients. "

The mailing, and a later one, provoked a request from the committee

that it be permitted to review the medical education presentations,

which are intended to provide doctors with educational credits to

keep their qualifications up to date.

A spokesman for Scios, Mark Wolfe, said that although a grant from

Scios financed the Natrecor presentations, they were run by an

independent company, which was responsible for their content. Mr.

Wolfe also said that the program had been authorized months before

the Braunwald committee recommendations.

Dr. Burnett of the Mayo Clinic said that Scios had sent Dr. Braunwald

review copies of the presentations, which he had distributed to other

committee members.

One cardiologist whose continuing medical education work was vetted

by Dr. Braunwald's committee, Dr. Mandeep Mehra, took exception to

the review.

" It is not appropriate for a panel of individuals to change a C.M.E.-

based presentation and exercise influence, " said Dr. Mehra, the

chairman of cardiology at the University of land Medical Center

in Baltimore.

Dr. Mehra, whose presentation in July was part of a videotaped

webcast, said the Braunwald committee had succeeded in having one

slide added to his presentation, emphasizing the panel's opposition

to outpatient Natrecor use.

Some Braunwald committee members were also troubled by what they saw

as an overly dense " Dear Doctor " letter sent to physicians on July

13, the first step in a company physician education program to tell

doctors that Natrecor should not be used in outpatients.

While the letter highlighted the panel's findings more prominently

than the news release had, Dr. Packer said the 11-page packet was too

long and " impossible for any doctor to get through. "

Dr. Burnett said that he had found the letter satisfactory but that

some members of the panel were dissatisfied with it. " Busy doctors

aren't going to sit there and page through this thing, " he said.

For Scios, the good news in the panel's report was the recommendation

that the Fusion II clinical trial of outpatient use of the drug

should continue. But Mr. Wolfe, the Scios spokesman, confirmed

yesterday that bad publicity about the drug had made enrolling

patients in Fusion II more difficult.

And regulators in India recently shot down an effort by a contract

research organization to enroll patients in Fusion II. They ruled in

July that the trials could not be conducted on Indian volunteers

because " there were several adverse reports about the product and it

was also not meant for use in India. "

In a statement yesterday, Scios said it still hoped that Indian

officials would eventually approve Fusion II study sites there.

Copyright 2005 The New York Times Company

FAIR USE NOTICE: This may contain copyrighted (© ) material the

use

of which has not always been specifically authorized by the copyright

owner. Such material is made available for educational purposes, to

advance understanding of human rights, democracy, scientific, moral,

ethical, and social justice issues, etc. It is believed that this

constitutes a 'fair use' of any such copyrighted material as provided

for in Title 17 U.S.C. section 107 of the US Copyright Law. This

material is distributed without profit.

[Guest guest]

& stung by its own Advisory Committee--Natrecor

should be strictly limited

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)

Promoting Openness, Full Disclosure, and Accountability

http://www.ahrp.org

FYI

Kudos go to Dr. Eugene Braunwald and the 10 members of the advisory

committee that he heads.

Contrary to & expectations, the committee recommended

extensive warnings to physicians against prescribing Natrecor to

outpatients.

When physicians begin to exercise honest professional judgement--

without regard for financial considerations--only then can trust be

restored to medicine!

Contact: Vera Hassner Sharav

212-595-8974

veracare@...

THE NEW YORK TIMES

August 9, 2005

Expert Panel Gives Advice That Surprises a Drug Maker

By STEPHANIE SAUL

Call it the advisory committee that keeps on giving advice.

After two medical studies questioned the safety of its popular heart

failure therapy Natrecor, the Scios unit of & turned

in April to a technique government and business often use to make

problems go away: it formed an outside advisory committee.

The company appeared to be taken aback in June, though, when it

learned just how fiercely independent its committee, led by Dr.

Eugene Braunwald of Harvard Medical School, turned out to be.

Rather than the milquetoast findings often returned by such advisory

panels, Dr. Braunwald's committee of 10 medical experts determined

that use of Natrecor, an expensive intravenous therapy, should be

strictly limited to acutely ill patients in hospitals. The committee

asked Scios to begin warning doctors against the drug's use in

outpatients, a treatment that had not been approved by the Food and

Drug Administration but that had helped turn Natrecor into a big

money maker.

The committee did not stop there. Over the last two months, some

members have expressed concern about the ways Scios has responded to

its recommendations. To register the committee's dissatisfaction, Dr.

Braunwald has sent Scios several letters and has gone so far as to

ask for changes in company-sponsored medical education presentations

about Natrecor, several members said.

" I think that, not surprisingly, the panel was concerned that the

recommendations be taken seriously, " said one member, Dr. C.

Burnett of the Mayo Clinic College of Medicine, who added that Dr.

Braunwald had recently told the committee that Scios was heeding its

concerns.

Dr. Braunwald, a renowned heart-failure specialist, did not respond

to several requests for an interview. Scios defended its response to

the Braunwald committee's recommendations and said it was preparing

to expand its physician outreach campaign warning doctors against

using Natrecor in outpatients.

The company also said that, as of July 29, it had revised a toll-free

telephone line that had coached doctors and their staffs on how to

file insurance claims for outpatient Natrecor infusions. Now, the

line warns against such use.

The original phone line helped spur accusations from several leading

cardiologists that Scios was promoting Natrecor for an unapproved

use. They sounded alarms after concluding that Natrecor might raise

the likelihood of potentially fatal kidney problems and questioning

whether the drug was worth its high cost - about $500 per infusion.

Although doctors can administer drugs to patients as they see fit, a

company's promotion of drugs for unapproved, or off-label, use is

illegal. Scios's Natrecor marketing program, and whether it actively

promoted an off-label use of the drug, is now the target of a Justice

Department investigation in Boston.

Financial analysts viewed Natrecor as a potential blockbuster when it

arrived on the market in 2001. But after the drug reached $400

million in sales last year, its sales are off 20 percent this year,

the company has said. The primary benefit of Natrecor, a manufactured

version of a naturally occurring cardiac hormone, is that it

temporarily makes breathing easier for a heart-failure patient.

Some committee members said that their concerns about Scios's

handling of their recommendations began soon after the panel reported

its findings to the company on June 13. The report's crucial finding

was unambiguous: Natrecor should not be used in outpatients.

But rather than simply disseminate the report, Scios created its own

prefacing news release. The committee's conclusion that Natrecor

should not be used in outpatient settings was not clearly stated

until the final page of the five-page company document. Instead, the

news release played up the panel's recommendation that Scios gather

further data by continuing with a clinical trial, called Fusion II,

to determine the drug's usefulness in outpatients.

" The press release emphasized a small aspect of our recommendations -

that clinical trials should continue; it de-emphasized or made little

mention of the more important take-home points of our

recommendations, " said Dr. Milton Packer, a cardiologist at the

University of Texas Southwestern Medical Center in Dallas who served

on the committee.

Dr. Packer also said that the committee members were shocked several

weeks later when they received invitations as part of a mass mailing

to enroll in a continuing medical education program, financed by

Scios, that seemed to promote the outpatient use of Natrecor, whose

chemical name is nesiritide.

" We were flabbergasted. " Dr. Packer said. " Scios was sponsoring

meetings to discuss nesiritide and its potential use in outpatients. "

The mailing, and a later one, provoked a request from the committee

that it be permitted to review the medical education presentations,

which are intended to provide doctors with educational credits to

keep their qualifications up to date.

A spokesman for Scios, Mark Wolfe, said that although a grant from

Scios financed the Natrecor presentations, they were run by an

independent company, which was responsible for their content. Mr.

Wolfe also said that the program had been authorized months before

the Braunwald committee recommendations.

Dr. Burnett of the Mayo Clinic said that Scios had sent Dr. Braunwald

review copies of the presentations, which he had distributed to other

committee members.

One cardiologist whose continuing medical education work was vetted

by Dr. Braunwald's committee, Dr. Mandeep Mehra, took exception to

the review.

" It is not appropriate for a panel of individuals to change a C.M.E.-

based presentation and exercise influence, " said Dr. Mehra, the

chairman of cardiology at the University of land Medical Center

in Baltimore.

Dr. Mehra, whose presentation in July was part of a videotaped

webcast, said the Braunwald committee had succeeded in having one

slide added to his presentation, emphasizing the panel's opposition

to outpatient Natrecor use.

Some Braunwald committee members were also troubled by what they saw

as an overly dense " Dear Doctor " letter sent to physicians on July

13, the first step in a company physician education program to tell

doctors that Natrecor should not be used in outpatients.

While the letter highlighted the panel's findings more prominently

than the news release had, Dr. Packer said the 11-page packet was too

long and " impossible for any doctor to get through. "

Dr. Burnett said that he had found the letter satisfactory but that

some members of the panel were dissatisfied with it. " Busy doctors

aren't going to sit there and page through this thing, " he said.

For Scios, the good news in the panel's report was the recommendation

that the Fusion II clinical trial of outpatient use of the drug

should continue. But Mr. Wolfe, the Scios spokesman, confirmed

yesterday that bad publicity about the drug had made enrolling

patients in Fusion II more difficult.

And regulators in India recently shot down an effort by a contract

research organization to enroll patients in Fusion II. They ruled in

July that the trials could not be conducted on Indian volunteers

because " there were several adverse reports about the product and it

was also not meant for use in India. "

In a statement yesterday, Scios said it still hoped that Indian

officials would eventually approve Fusion II study sites there.

Copyright 2005 The New York Times Company

FAIR USE NOTICE: This may contain copyrighted (© ) material the

use

of which has not always been specifically authorized by the copyright

owner. Such material is made available for educational purposes, to

advance understanding of human rights, democracy, scientific, moral,

ethical, and social justice issues, etc. It is believed that this

constitutes a 'fair use' of any such copyrighted material as provided

for in Title 17 U.S.C. section 107 of the US Copyright Law. This

material is distributed without profit.