Expanded Access Programs May Facilitate Prelaunch Market Access in Canada

Neelima Firth, M.B.A.

Introduction

Oftentimes, patients with serious or immediately life-threatening diseases or conditions, who have tried approved therapies without success, are interested in investigational therapies. These patients and their treating physicians are very interested in accessing drugs under development, especially if the early results of clinical trials are encouraging.  Notably, several organizations, including the Abigail Alliance, have lobbied governments to make access to investigational medicines easier for these patients and their physicians.

The most common way for a patient to receive an investigational medicine is as a registered participant in an approved clinical trial.  However, many patients are not eligible to participate in a clinical trial due to the trial’s inclusion and/or exclusion criteria or because of geographic location.  Through expanded access programs, drug companies can provide appropriate patients with drug therapies that are still under investigation.

What are Expanded Access Programs

Expanded access programs provide patients who are not eligible to participate in a clinical trial with early access to investigational or unavailable drugs.  Expanded access programs are sometimes termed early access protocols, ‘compassionate use’ programs, named patient programs or single person INDs.

Key Benefits

Expanded access programs enable companies to provide early market access to important medicines before obtaining regulatory approval for these drugs. When a drug is in the prelaunch phase or has been approved and launched in the United States, the drug’s manufacturer is likely to receive requests for the drug from around the world. The company can fulfill this demand, when appropriate, by using an expanded access program. Expanded access programs can also provide a company with additional revenue, insight into the product’s value to physicians and patients, and new relationships with key opinion leaders across the globe.

There has been one analysis that concluded that an expanded access program had a significant impact on the market share of a drug within the first year of launch.(2)

Some companies  also use these programs as a cost efficient distribution channel for products with small numbers of patients in that country, even after they are approved.

Canada’s Special Access Programme (SAP) provides access to non-marketed products. In some cases, these products are on the market in the United States or EU but, for business reasons, the manufacturer has decided not to market the product in Canada. The SAP gives physicians access to non-marketed products for patients with serious or life-threatening illnesses. The SAP also allows manufacturers to sell the products

Special Access Programme in Canada (SAP)

Under Canada’s Food and Drugs Act, Health Canada (the Canadian government’s health ministry) is authorized to regulate the safety, efficacy, and quality of therapeutic products.  Patient access to an investigational or unauthorized drug is usually limited to participants in clinical trials sponsored by a manufacturer and authorized by Health Canada through a clinical trial application.

However, Health Canada has permitted the sale of unauthorized drugs for medical emergencies since 1966. In the 1990s, Health Canada expanded the term ‘medical emergency’ to include serious and life-threatening conditions. Before then, it was limited to: ‘an injury or condition that poses an immediate threat to a person\\\'s health or life which requires medical intervention’.  When a drug is not available to a patient through a clinical trial, Health Canada may allow an exemption from the Food and Drugs Act to permit the sale of an unauthorized drug for a medical emergency.  According to the Food and Drugs Act, companies may provide the drugs for free or they may charge patients for these drugs. (3,4)

The types of drugs authorized for use under the SAP include pharmaceutical, biologic and radiopharmaceutical products that are not for sale in Canada.  Most of these drugs treat patients with life threatening diseases or serious conditions such as intractable depression, epilepsy, transplant rejection, hemophilia and other blood disorders, terminal cancers and AIDS.  The SAP is also designed to help in response to specific public health crises, such as the outbreak of a communicable disease, by providing a mechanism for access to nonmarketed drugs.

Practioners treating patients with serious or life-threatening conditions request Special Access in cases where conventional therapies have failed, are unavailable or are unsuitable.  Emergency access is intended to be exceptional.

Roles and Responsibilities

Health Canada

The SAP decides whether to authorize or deny SAP requests from doctors on a case-by-case basis. The agency takes into account the nature of the medical emergency, the availability of currently marketed alternatives, and the safety and efficacy of the requested medicine.  

The SAP grants access to only a limited quantity of the requested drug and for a limited time period (usually six months of treatment is authorized).  Additional or repeat treatments must be ordered through the SAP request process.  Access to drugs that are currently undergoing regulatory review is  limited until the review is complete.

Physician or Practitioner

The physician initiates a request and ensures that the decision to prescribe the drug is supported by credible evidence from clinical publications, investigator brochures, or manufacturer. The treating physician is  required to account for all drug supplied and to report to the SAP and the manufacturer the outcomes of the drug’s usage and any adverse events.

Manufacturer

The key decision for a manufacturer is to consider if they wish to sell the drug to physicians through the SAP. A manufacturer is under no obligation to sell an unauthorized drug and the SAP cannot compel a manufacturer to do so. The manufacturer also decides the price of the drug or may decide to provide it free and may consult with Canada’s Patented Medicine Prices Review Board, if necessary.  They can also impose conditions on the drug’s sale to ensure that it is used in accordance with the latest information available. Manufacturers may:

Historic Examples of Applications of the Expanded Access Programs

Erbitux® (cetuximab) was available through the SAP prior to its commercialization in Canada in October 2008. Although Health Canada approved the product in 2005, Erbitux did not enter the Canadian market at that time because the Patented Medicine Prices Review Board and Bristol-Myers Squibb could not agree on the price for the drug. While that discussion was ongoing, some patients had access to the product through the SAP.(5,6)

Generex Biotechnology Corporation received SAP authorization from the Therapeutic Products Directorate of Health Canada for a patient-specific, physician-supervised treatment of type 1 diabetes mellitus with Generex Oral-lyn™ (oral insulin). Generex regarded this information as important enough to list in its U.S. Securities and Exchange Commission filing in May 2008.(7)

In some cases, a product that is not licensed in Canada is routinely used in that country to treat serious diseases, such as cancers. An example is Eloxatin® (oxaliplatin), a chemotherapy drug that has become the standard of care for colorectal cancer. The manufacturer, Sanofi-Aventis, has distributed this product in Canada since 1999 through the SAP program. It was only in 2007, that Sanofi-Aventis decided to seek a license from Health Canada to market the drug. (8)

Thalidomide is an example of the importance of administering expanded access programs appropriately.  Thalidomide has been available in Canada through the SAP for treating multiple myeloma. Because the drug was not licensed and was only available in Canada through the SAP, the price was not regulated. By 2008, the price had increased nine-fold. That same year, Canada’s Patented Medicine Prices Review Board ruled that it had jurisdiction over the drug and determined that its price was excessive. The board therefore imposed retroactive price controls on thalidomide. (9)

Best-In-Class Recommendations and Challenges

Expanded access programs can provide a number of important benefits to patients, physicians, and drug manufacturers. These programs offer early access to potentially life-saving or life-improving drug therapies for appropriate patients before these therapies receive regulatory approval. The programs also provide market access to orphan drugs for patients with rare disorders.

An expanded access program should be considered as part of a market access strategy for a product or portfolio. A company’s decision to offer such a program needs to take into consideration:

The strategic consideration should also include any pre-market conditioning that can support the eventual launch of the product. Some companies also use these programs to ensure global access to products where it would not be economically viable to go through a full regulatory strategy.

Once a company decides to create an expanded access program, it needs to establish clear business rules, such as which drugs to make available, the criteria for providing the drugs, and whether to charge for the drugs or offer them at no cost to patients. If a company plans to charge for a product, it must decide on the appropriate price as part of its worldwide pricing strategy.

Any expanded access program exists in a highly regulated environment. Manufacturers must review important legal, regulatory, and clinical information for each drug with regard to the specific dictates of each expanded access program under consideration. Companies should adopt standard operating processes for reviewing and approving product requests and for shipping the products. Because companies must review and approve product requests on a case-by-case basis, they need clear and adequate documentation at each step of the process.  

Companies that choose to utilize expanded access programs also need a distribution process for the products; such processes are often outside a company’s normal ordering and shipping channels.

Because of the mandated legal, regulatory, and clinical frameworks that exist around the use of these programs, companies must report, monitor, and audit their processes on a regular basis to ensure that their processes are in alignment with all of the requirements. It is important that manufacturers allocate adequate internal resources to their expanded access programs and work with vendor and consultancies who are experienced in successfully working in this environment.

Expanded access programs require significant management to establish. The decision to implement such a program must therefore take into account the company’s clinical, regulatory, and market access strategy for its products. Companies stand to gain many benefits from providing early access to a product, including the creation of a group of patients and physicians who are already aware of the product’s benefits and can support launch activities, as well as an early revenue stream.

Conclusions

An expanded access program is an important part of a manufacturer’s global commercialization strategy. The benefits of such programs to manufacturers include expanded global reach, the potential for the creation of new revenue streams, and the ability to gather important clinical experience and insight. Patients value these programs because they receive potentially life-saving or life-improving treatment for serious diseases or conditions, after having exhausted the use of approved or authorized treatments. Many governments support the use of these programs as a means of providing their citizens with access to important treatments that may otherwise be unavailable.

The Aequitas Group is a San Diego based healthcare consulting firm that helps companies develop global reimbursement and commercialization strategies. The Aequitas Group has expertise in evaluating and successfully executing a range of expanded access patient programs for drug manufacturing clients. .

References

1.     Charging For Investigational Drugs Under An Investigational New Drug Application; Expanded Access To Investigational Drugs For Treatment Use, Final Rule Federal Register 71 (13 August 2009):40873-40945

2.         Implementing a pre-launch named patient programme: Evidence of increased market share
AK Bates. Journal of Medical Marketing, 2008, 8(4):1745-7904

3.        Health Canada. Special Access Programme for Drugs. Guidance Document for Industry and Practitioners. Effective date: January 28, 2008.
http://www.hc-sc.gc.ca/dhp-mps/acces/drugs-drogues/sapg3_pasg3-eng.php#4

4.    Health Canada. Special Access Programme. Special Access Request Form A, and Future Use Request Form B, Follow-up Form C.
    http://www.hc-sc.gc.ca/dhp-mps/acces/drugs-drogues/index-eng.php

5.    Bristol Myers Squibb. BMS Canada Commercializes Erbitux for Advanced Colorectal Cancer. Press release. October 29, 2008
http://www.bmscanada.ca/bms/news/?news_id=2454

6.    FiercePharma. BMS Swallows Canada’s Erbitux Price. April 29, 2008.
http://www.fiercepharma.com/story/bms-swallows-canada-s-erbitux-price/2008-04-29#ixzz0PEvgqYNZ

7.    Steffens RJ. Generex Biotech’s Oral-lyn granted special access authorization by Health Canada. Seeking Alpha.  May 5, 2008.
http://seekingalpha.com/article/75652-generex-biotech-s-oral-lyn-granted-special-access-authorization-by-health-canada

8.    Priest L. Trade gambit doubles cost of cancer medicine. Reprinted from the Globe and Mail, May 25, 2007, by the Colorectal Cancer Association of Cancer.
    http://www.colorectal-cancer.ca/en/news-and-resources/trade-medicine/

9.    Priest L. Ottawa moves to reduce price of drug after cancer patients complain of gouging. Reprinted from the Globe and Mail, January 31, 2008, by Myeloma Canada.
http://www.myelomacanada.ca/docs/ottawa%20moves%20to%20reduce%20price%20of%20drug%20013108.pdf