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Non-Sedating AntihistaminesRx-to-OTC Switch

NDAC & PADAC Joint Meeting

Non-Sedating AntihistaminesRx-to-OTC Switch

NDAC & PADAC Joint Meeting

May 11, 2001

François Nader, MD

Senior Vice-President

Medical & Regulatory Affairs, North America

Aventis Pharmaceuticals, Inc.

May 11, 2001

François Nader, MD

Senior Vice-President

Medical & Regulatory Affairs, North America

Aventis Pharmaceuticals, Inc.

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OverviewOverview

• A switch of Allegra® (fexofenadine) from a prescription status to OTC would be premature

• Allegra is a relatively new product

• A switch of the 2nd generation antihistamines would be inappropriate, unnecessary, and potentially adverse to the interest of patient safety

• This process today is unprecedented and unwarranted

• A switch could have direct and indirect unintended patient safety and public health implications

• A switch of Allegra® (fexofenadine) from a prescription status to OTC would be premature

• Allegra is a relatively new product

• A switch of the 2nd generation antihistamines would be inappropriate, unnecessary, and potentially adverse to the interest of patient safety

• This process today is unprecedented and unwarranted

• A switch could have direct and indirect unintended patient safety and public health implications

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Allegra® Is Still a Relatively New ProductAllegra® Is Still a Relatively New Product

• Allegra launches:

– 1996: Allegra 60 mg bid

– 2000: Allegra 180 mg qd, Allegra 60 mg tabletPediatric use -- Allegra 30 mg

• Ongoing clinical development:

– Asthma, atopic dermatitis and additional pediatric development

– The FDA has asked us to assess unanticipated adverse reactions in pediatrics

– The FDA also asked us to run ECG’s on all pediatric patients included in the trials

• Ongoing post-approval safety and effectiveness trials

• Ongoing extensive safety monitoring of the post-marketing experience

• Allegra launches:

– 1996: Allegra 60 mg bid

– 2000: Allegra 180 mg qd, Allegra 60 mg tabletPediatric use -- Allegra 30 mg

• Ongoing clinical development:

– Asthma, atopic dermatitis and additional pediatric development

– The FDA has asked us to assess unanticipated adverse reactions in pediatrics

– The FDA also asked us to run ECG’s on all pediatric patients included in the trials

• Ongoing post-approval safety and effectiveness trials

• Ongoing extensive safety monitoring of the post-marketing experience

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Seldane: Over 10 Years on the Market & 24 Million

Patient Years Experience

Seldane: Over 10 Years on the Market & 24 Million

Patient Years Experience

• Marion Merrell Dow was evaluating the OTC switch of Seldane

• Neither the company nor the FDA believed there were any significant safety issues associated with the drug

• Signals on drug-drug interactions leading to serious cardiotoxicity when the drug was not used as labeled

• Seldane was withdrawn from the US market before it ever went OTC

• Conclusions:

– Process, time on the market, and patient exposure are critical

– Once a drug is sold OTC, the quality and quantity of adverse event reports are no longer reliable

– A switch would be premature

• Marion Merrell Dow was evaluating the OTC switch of Seldane

• Neither the company nor the FDA believed there were any significant safety issues associated with the drug

• Signals on drug-drug interactions leading to serious cardiotoxicity when the drug was not used as labeled

• Seldane was withdrawn from the US market before it ever went OTC

• Conclusions:

– Process, time on the market, and patient exposure are critical

– Once a drug is sold OTC, the quality and quantity of adverse event reports are no longer reliable

– A switch would be premature

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Unprecedented & UnwarrantedSwitch Process

Unprecedented & UnwarrantedSwitch Process

• Blue Cross has requested extraordinary action with respect to 3 distinct drug products

• The 3 manufacturers oppose the switch, in part, because of unanswered potential safety and public health questions

• The non-sedating antihistamines are chemically and pharmacologically different

• Traditionally, the manufacturer initiates a switch by filing a comprehensive NDA supplement. In this case,

– No supplement has been filed

– No studies have been performed

– No actual OTC use or labeling comprehension studies conducted

• Limited time and absence of guidance from the FDA

• Blue Cross has requested extraordinary action with respect to 3 distinct drug products

• The 3 manufacturers oppose the switch, in part, because of unanswered potential safety and public health questions

• The non-sedating antihistamines are chemically and pharmacologically different

• Traditionally, the manufacturer initiates a switch by filing a comprehensive NDA supplement. In this case,

– No supplement has been filed

– No studies have been performed

– No actual OTC use or labeling comprehension studies conducted

• Limited time and absence of guidance from the FDA

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The Switch Could Have Unintended Patient Health and Safety Consequences

The Switch Could Have Unintended Patient Health and Safety Consequences

• Difficult for patients to accurately diagnose their condition, identify their triggers, and determine the appropriate course of treatment

• Impact due to misdiagnosis and co-morbidities

• Impact on special populations such as pediatrics and the elderly

• Short-term gain as a result of a shift of medication costs to patients could increase overall healthcare cost substantially

• Difficult for patients to accurately diagnose their condition, identify their triggers, and determine the appropriate course of treatment

• Impact due to misdiagnosis and co-morbidities

• Impact on special populations such as pediatrics and the elderly

• Short-term gain as a result of a shift of medication costs to patients could increase overall healthcare cost substantially

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The Switch Could Have Unintended Patient Health and Safety Consequences

The Switch Could Have Unintended Patient Health and Safety Consequences

• The patient, not the doctor, will have to diagnose the condition

• The patient, not the doctor, will have to select what medications to take and how to take them

• The patient, not the insurance company, will have to pay for the medications

• Possible increased use of the less expensive sedating antihistamines

• The patient, not the doctor, will have to diagnose the condition

• The patient, not the doctor, will have to select what medications to take and how to take them

• The patient, not the insurance company, will have to pay for the medications

• Possible increased use of the less expensive sedating antihistamines

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Blue Cross of California PetitionBlue Cross of California Petition

• No evidence that a switch will benefit patient health and safety

• Blue Cross argues that the current sedating antihistamines available OTC are “dangerous”

– Yet, Blue Cross’ own formulary continues to reserve non-sedating antihistamines for patients “who have failed or are unable to tolerate over-the-counter therapy”

– In fact, the FDA has stated that the sedating antihistamines are safe as currently labeled, and therefore we do not believe there is a basis for the petition in the first place

• Blue Cross argues that patients are being denied access to non-sedating antihistamines

• No evidence that a switch will benefit patient health and safety

• Blue Cross argues that the current sedating antihistamines available OTC are “dangerous”

– Yet, Blue Cross’ own formulary continues to reserve non-sedating antihistamines for patients “who have failed or are unable to tolerate over-the-counter therapy”

– In fact, the FDA has stated that the sedating antihistamines are safe as currently labeled, and therefore we do not believe there is a basis for the petition in the first place

• Blue Cross argues that patients are being denied access to non-sedating antihistamines

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Liability ConcernsLiability Concerns

• Until we have confidence that a switch will not harm patients, we are not prepared to subject physicians, pharmacists, or the company to liability claims based on a premature entry into the OTC marketplace

• Until we have confidence that a switch will not harm patients, we are not prepared to subject physicians, pharmacists, or the company to liability claims based on a premature entry into the OTC marketplace

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In SummaryIn Summary

• Shifting the diagnosis responsibility, the treatment accountability and the cost burden from managed care to the patients may have direct and indirect patient-safety and public-health implications

• The patients could be playing a costly trial-and-error game with their health, their quality of life and their money

• Allergic rhinitis management could switch from a physician driven diagnosis and treatment and a reimbursed medication to a self-diagnosis, a self-chosen treatment and self payment

• There can be no substitute for a reliable process, time on the market, and patient exposure to characterize rare adverse events in a timely manner

• Shifting the diagnosis responsibility, the treatment accountability and the cost burden from managed care to the patients may have direct and indirect patient-safety and public-health implications

• The patients could be playing a costly trial-and-error game with their health, their quality of life and their money

• Allergic rhinitis management could switch from a physician driven diagnosis and treatment and a reimbursed medication to a self-diagnosis, a self-chosen treatment and self payment

• There can be no substitute for a reliable process, time on the market, and patient exposure to characterize rare adverse events in a timely manner

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FDA QuestionsFDA Questions

• Should fexofenadine be made available for OTC use?

– We believe that a switch would be premature

• What concerns should be addressed prior to OTC marketing?

– Continue assessing the post-marketing data

– Pursue the post-approval clinical trials to further characterize fexofenadine in a prescription environment

– When timely and appropriate, conduct additional studies to assess the impact of an OTC switch

• Should fexofenadine be made available for OTC use?

– We believe that a switch would be premature

• What concerns should be addressed prior to OTC marketing?

– Continue assessing the post-marketing data

– Pursue the post-approval clinical trials to further characterize fexofenadine in a prescription environment

– When timely and appropriate, conduct additional studies to assess the impact of an OTC switch

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Non-Sedating AntihistaminesRx-to-OTC Switch

NDAC & PADAC Joint Meeting

Non-Sedating AntihistaminesRx-to-OTC Switch

NDAC & PADAC Joint Meeting

May 11, 2001

François Nader, MD

Senior Vice-President

Medical & Regulatory Affairs, North America

Aventis Pharmaceuticals, Inc.

May 11, 2001

François Nader, MD

Senior Vice-President

Medical & Regulatory Affairs, North America

Aventis Pharmaceuticals, Inc.

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• Switching fexofenadine to OTC would be premature

• There are no compelling reasons to switch any of the non-sedating antihistamines

• Switching fexofenadine to OTC would be premature

• There are no compelling reasons to switch any of the non-sedating antihistamines