ERDCA

Lobbying for the "Exceptionally Rare Diseases and Conditions Act"

- a unique pathway for new drugs for sarcoma patients

Mark Thornton, M.D., Ph.D.

President and Chairman

Sarcoma Foundation of America

The U.S. Food and Drug Administration has never approved a drug for use for sarcoma patients. Current chemotherapy regimens are from studies conducted over 20 years ago. Today, this has changed somewhat in that there are a couple of new drugs in development for sarcoma. But even these agents may end up benefiting only a small fraction of sarcoma patients, and leave many subtypes of sarcoma patients with no options and with nothing on the horizon. Therefore, an important legislative initiative for the sarcoma community is passage of the Exceptionally Rare Diseases and Conditions Act. This legislative initiative by the Sarcoma Foundation of America (SFA) would result in modest reform of the Food, Drug and Cosmetic Act to result in a unique pathway for drug development for patients with rare cancers and other extraordinarily rare diseases. This pathway could be utilized by a pharmaceutical company in situations where clinical trials are impossible to perform, yet clinical data and other supportive data present a compelling picture that the new agent would provide some benefit to the patient. The bill requires demonstration by the drug sponsor to the FDA that indeed clinical trials cannot be done, and are even incapable of utilizing the "accelerated approval" mechanisms that exist to help foster some types of drugs approvals. Because of the requirement for “surrogate endpoints” to be used for accelerated approval, and because of the lack of surrogate endpoints for all sarcomas except for GIST, the FDA is forced to require that sarcoma clinical trials have “overall survival” endpoints that require a clinical trial to be upwards of a thousand patients ( true “Catch-22 for sarcoma and other ultra-rare diseases).

The language in the bill sets very strict criteria that the drug company and FDA must follow, and has safeguards preventing abuse of approval based on more "relaxed" standards than normally seen. We appreciate how sensitive some advocacy groups and other bodies are to the perception of "lower" standards for efficacy approval for new agents for life-threatening diseases. Read the bill and judge for yourself. We feel that since the legislation completely empowers the FDA to decide whether the new drug is of overall value to the patient, we can trust them to make the right call for us. This unique pathway is envisioned for only extraordinary circumstances, but we feel that the pathway might occasionally provide some hope to some sarcoma patients who otherwise would die of their ailment without the therapies that could be approved utilizing this pathway.

If a significant number of people in a significant number of states and Congressional districts can be mobilized, this could make a difference in the success of this effort. If you are willing to gather lists of supporters through your networks, please email me. Let us know the names, Congressional district and contact information for such troops. As needed, the SFA would then coordinate and match volunteers to key lawmakers. All that would be required of volunteers is letter writing capability, and if desired the SFA could provide the volunteers with sample text for the letter. Our first effort is finding a member of Congress to introduce this legislation.

The DISCUSSION DRAFT of the proposed legislation follows

109th CONGRESS 2d Session

S. __

M_. ______ introduced the following bill; which was referred to the Committee on ______________

A BILL

To amend the Federal Food, Drug, and Cosmetic Act to accelerate the approval of drugs for patients with exceptionally rare diseases or conditions, and for other purposes.

SEC. 1. SHORT TITLE.

This Act may be cited as the "Exceptionally Rare Diseases and Conditions Act".

SEC. 2. FINDINGS.

Congress makes the following findings:

(1) There are populations of children and adults in the United States who suffer from exceptionally rare diseases and conditions. Those patients often lack approved treatments for those diseases and conditions due to the difficulties associated with conducting studies in extremely small patient populations.

(2) Existing mechanisms of the Food and Drug Administration for approval and licensure of drugs and biologics may deny the benefits of medical progress to individuals affected by exceptionally rare diseases and conditions. In particular, current mechanisms for approval or licensure of agents for exceptionally rare diseases and conditions typically necessitate curative or near-curative efficacy in order to obtain approval, inhibiting new drug and biologic development.

(3) In the case of individuals affected by exceptionally rare diseases and conditions, the measures for analysis of animal and human data can be adapted to allow a finding that a new product is effective, despite the difficulties associated with conducting clinical trials.

(4) Appropriate controls can be put in place to ensure that individuals affected by exceptionally rare diseases and conditions are protected from unreasonable risks, to prevent unapproved uses, and to ensure that, when feasible, confirmatory research is conducted on treatments approved or licensed under this provision.

SEC. 3. DRUGS TO TREAT EXCEPTIONALLY RARE DISEASES AND CONDITIONS.

(a) In general.--Subchapter B of chapter V of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360aa and following) is amended by adding at the end the following:

"SEC. 529. DRUGS TO TREAT EXCEPTIONALLY RARE DISEASES OR CONDITIONS.

"(a) In General.--Notwithstanding any other provision of law, the sponsor of a drug or biologic for treatment of an exceptionally rare disease or condition that is designated under section 526 may submit an application to the Secretary under section 505(b) of this Act or section 351 of the Public Health Service Act for approval or licensure in accordance with this section.

“(b) Exceptionally Rare Disease or Condition.-- The term "exceptionally rare disease or condition" means any rare disease or condition for which the application of standard or surrogate measures of efficacy is not reasonably feasible due to the exceptionally small number of individuals affected. A disease or condition which affects less than 4000 individuals in the United States shall be presumed to be exceptionally rare.

“(c) Approval process.--

"(1) Content of application.--Any application under section 505(b) of this Act or section 351 of the Public Health Service Act for approval or licensure of a new drug or biologic to treat an exceptionally rare disease or condition shall include the following:

"(A) all available clinical data and information on use of the drug or biologic in the population affected by the exceptionally rare disease or condition;

“(B) epidemiological or other evidence demonstrating that the disease or condition treated by the drug or biologic is exceptionally rare;

"(C) a demonstration that adequate and well-controlled trials establishing efficacy, including trials establishing an effect on surrogate endpoints or clinical endpoints other than survival or irreversible morbidity, are not reasonably feasible due to the size of the patient population;

“(D) a demonstration that the safety of the product has been established;

“(E) a demonstration that there is a reasonably well-understood biological basis for the effectiveness of the drug or biologic in treating the exceptionally rare disease or condition;

“(F) studies in animals, data on kinetics and pharmacodynamics, and other information demonstrating that the product would be expected to provide a reasonably meaningful clinical benefit over any existing treatments; and

"(G) a plan providing assurance that a system of controls over the product can be maintained in order to both prevent unapproved uses and gain additional information on the safety and efficacy of the product.

"(2) Approval.--

"(A) The Secretary may grant approval or licensure for a new drug or biologic product to treat an exceptionally rare disease or condition if the Secretary determines that the application for such approval or licensure meets the requirements of paragraph (1) and the product can be expected to provide a reasonably meaningful clinical benefit over any existing treatments. In approving or licensing any such product, the Secretary may establish conditions of approval or licensure as set forth in subparagraph (B).

"(B) Conditions of approval or licensure.--As conditions of approval or licensure, the Secretary may require that the sponsor—

"(i) conduct appropriate post-approval clinical studies to further verify and characterize the efficacy of the product when feasible in light of scientific developments and the size and distribution of the patient population;

“(ii) maintain a patient registry associated with surveillance measures necessary to gain additional information about the safety and efficacy of the product;

“(iii) impose controls over the distribution of the product to the extent necessary to prevent unapproved uses;

"(iv) submit copies of all advertising and promotional materials related to the drug to the Secretary at least 30 days prior to the dissemination of the materials;

"(v) prominently disclose the limited data supporting the effectiveness of the drug in any advertising and promotional materials; and

"(vii) disseminate advertising or promotional material only upon written notification from the Secretary that the advertising or promotional material complies with the Act.

"(3) Inapplicability of user fees.--Notwithstanding any other provision of this Act, parts 2 and 3 of subchapter C of chapter VII shall not apply to applications and approvals for drugs to treat exceptionally rare diseases or conditions as described under this section.".

Where can one learn about the drug approval process in the U.S.?

The National Cancer Institute maintains a webpage "Understanding the Approval Process for New Cancer Treatments". Note, in particular the five links at the top of the left hand column of this webpage: FDA's Role, Clinical Trials, Special Needs, Q&A: Off-Label Drugs, and History.

The mission Center for Drug Evaluation and Research (CDER) of the U.S. Food and Drug Administration (FDA) has the mission to assure that safe and effective drugs are available to the American people.

	"The CDER Handbook" contains a section on "New Drug Development and Review.
	You can also download the complete CDER Handbook by clicking on the "Print Handbook" icon on the above webpage.
	There are an extensive number of useful links related to drugs on CDER's webpage, "Information about the Products We Regulate".

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