Science / Health

Canada lacking orphan drug policy for rare conditions

September 26, 2006 | Melanie Chambers

Some MDs go to bat for patients, but getting drugs covered a tough battle

TORONTO | Some doctors are having difficulty getting “orphan drugs” for their patients and say Canada is falling behind other countries in providing access and funding for expansive medications to treat rare disorders.

Physicians attempting to obtain expensive and rare medications for their patients find the process time-consuming and frustrating, but many are willing to go the extra mile because these treatments are often the only options available to treat potentially life-threatening disorders.

There are two separate and unrelated steps before patients get access to all prescription drugs. First, the drug must be approved by Health Canada after being submitted by the manufacturer for a formal review. Once the drug is approved, a completely separate process occurs; provincial drug programs, either by themselves or through the Common Drug Review (CDR) process, receive submissions from the drug manufacturer. Then, based on efficacy and cost-benefit, a decision about paying for the drug is made. For orphan drugs, which are used to treat rare disorders, patients and doctors often have to go to Health Canada’s Exceptional Drug Release program to gain approval and then must petition those running provincial formularies or the CDR to see if the provinces will fund use of orphan drugs.

Patient advocacy groups involved in obtaining and funding drugs see the system as being too slow and too cumbersome. “The Canadian health-care system was never designed to take care of people with rare disorders,” said Dr. Durhane Wong-Rieger (PhD), president of the Canadian Organization for Rare Disorders, an independent organization that supports these special patients.

She said the doctor’s role as advocate is crucial; often the first question decision-makers, drug reviewers or politicians ask is: “What does the physician recommend?” But not all physicians feel equipped to deal with rare disorder cases. Some feel the chances of getting approval are slim, and others are reluctant to be perceived as too political.

The interprovincial CDR process recommends new drugs for provincial funding. Based on the CDR recommendation, or on their own review, each province decides whether or not to pay for medication. The CDR’s criteria are safety, cost-effectiveness and efficacy of the drug. Provincial health administrators look at similar criteria—and their budget.

For rare disorders, adequate data to support these criteria are lacking or considered inadequate: Most rare medications have had randomized clinical trials but the rarity of the disorder means there are too few patients available to support a strong statistical evaluation. This gap then means many rare disorder medications never make it past the approval stage.

Other countries have gotten around this by establishing orphan drug policies that provide incentives to drug companies to develop drugs for rare disorders. Canada is the only developed country without an orphan policy, which means Canadians have access to fewer new drugs for rare disorders.

With only a few drug companies pursuing treatment options for rare disorders and only a few patients requiring treatment, medications can cost hundreds of thousands of dollars, a hefty price tag that becomes the major barrier for approval by the CDR.

“At $300,000 a year, these drugs will never be what we call cost-effective, so even if they did save lives, they would say it is not cost-effective because they cost too much per life,” said Dr. Michael West, head of nephrology at Dalhousie University in Halifax, who advocates for Fabry patients in Nova Scotia.

Fabry disease is a rare genetic disorder that affects about 200 patients in Canada. This progressive condition affects many areas of the body but most patients will develop renal failure, cardiomyopathy, cardiac arrhythmia and recurrent strokes.

Physicians may request treatment for rare diseases not approved by Health Canada through the federal Special Access Program (SAP). But physicians who request these unlicensed drugs must take full responsibility for the drugs’ use, requiring physicians to report back to the government on any adverse effects or problems.

“We have to justify as much as we can, the reason why we want to use it and that it is safe. Usually it’s a medication that may have been used somewhere else,” said Dr. Robin Casey, director of the Inherited Metabolic Diseases Clinic at Alberta Children’s Hospital in Calgary. Sometimes drug companies make the product available, but if they don’t, physicians must find reimbursement.

And again, when patients wish to be reimbursed by their provinces, it’s up to their individual physicians to request funding for “extraordinary” cases, which rare disease medications fall under. Each province, save for British Columbia and Quebec, has a program for individualized special access that is approved on a “case-by-case” basis.

But some of the doctors who use the federal SAP and/or provincial special request for funding have become disenchanted.

Dr. Joe Clarke, director of the Genetic Metabolic Diseases Program at the Hospital for Sick Children at the University of Toronto, began helping patients with Gaucher disease obtain funding about 15 years ago. Although he’s used Ontario’s special request forms (referred to as Section 8 forms), he said these forms alone cannot solve the problems associated with rare disorder funding.

“Sometimes you’ll get a positive answer for one situation and in another might get a negative answer. There seems to be a lack of guidelines for Section 8 applications,” said Dr. Clarke.

Some doctors resort to more creative ways to secure access and funding. They search for clinical trials where they can enrol patients in need of orphan drugs. Not only can taking part in clinical trials result in free access to drugs, but these trials provide much-needed scientific data about rare disorders.

However, to enter a clinical trial, patients must fit into a narrow range of disease criteria. And even if they manage to find a trial, only half of the clinical trial patients typically receive free medication for the duration of the trial, as others are on a placebo. And when the trial ends, so does the drug supply.

To circumvent this predicament, some physicians try to find evidence about treatments for similar conditions to support their special access applications. This can be a challenge because there’s no clear evidence that the drug is of value to the patient with the rare disorder.

Another temporary option for doctors is to ask drug companies to supply a drug on a compassionate basis. But, this is not a realistic solution because it’s not the manufacturers’ responsibility to supply free drugs.

In Nova Scotia, about 23 Fabry patients, through dedicated work from doctors and support groups, were able to secure enzyme replacement therapies (ERT), the only treatment available for Fabry disease, either through participation in a clinical trial or from compassionate use medications. For five years, the pharmaceutical company Genzyme provided Fabrazyme while Shire Human Genetic Therapies provided Replagal. But when the trials ended and the drug companies cut off the drug supply, the patients went off medications.

Meanwhile, in 2004, when ERT did become licensed in Canada, there was still no provincial funding established.

The CDR then recommended against reimbursement from the provinces because of a lack of long term clinical outcomes.

And while some provinces, including Nova Scotia with a major portion of Fabry patients in Canada, took this recommendation and didn’t fund therapies, some other provinces, such as Alberta, part of Quebec and British Columbia, did fund ERT. This was both distressing for the patients and the doctors who had worked tirelessly for their patients for years and had seen patient improvement on ERT.

In many cases, it’s the patients who find therapies through their own research. When Betty McPhee of Ontario was diagnosed with Waldenstrom’s macroglobulinemia, a rare form of non-hodgkins lymphoma, her doctor used a SAP to provide therapy for a time.

More recently, through her own research efforts and the recommendation and help of Waldenstrom’s specialist, Dr. Steven Treon at the Dana Farber Cancer Institute in Boston, she wanted to try another therapy called Maintenance Rituxan. This time, while open to MR, her Ontario doctor refused to fill out a SAP application. He said there was no way it would be approved for Waldenstrom as it isn’t funded for other lymphoma patients.

While McPhee’s therapy isn’t a matter of life or death, it’s a quality of life issue, she says. “The challenges I have encountered in getting funding for this treatment highlight the need for special funding for rare disorders and for an orphan drug policy in Canada.”

However, there may be hope on the horizon. In an unprecedented move, federal and provincial governments and industry are creating a tripartite funding agreement to provide enzyme replacement for Fabry patients for three years while data are collected on its efficacy.

“It was done because of the recognition by government that there was a need to deal with this disease, and these incredibly expensive drugs, and that it wasn’t going to be dealt with by the common drug review,” said Dr. West.

Dr. Casey is optimistic, however, that “the problem we’re facing is there are more drugs of this sort that have already been approved in Canada, but for which there is no mechanism for funding. We hope something like the tripartite agreement will become at least a pointed direction for dealing with these other medications.”

And in September 2004, the federal, provincial and territorial ministers of health established the National Pharmaceutical Strategy. One of the nine objectives of this strategy is to review expensive drug reimbursements for rare disorders. “The framework is expected to improve Canadians’ understanding of rare diseases,” said Carole Saindon, a Health Canada spokesperson. “This will ultimately align the current regulatory and reimbursement programs and processes.”