How to prove orphan drug cost-effectiveness and safety to secure market access

Andrew Mumford

CEO, Initiate Consultancy

Pharmaceutical market access — getting a drug paid for (or ‘reimbursed’) by a country’s healthcare system so it can be used by clinicians — is a complex process, especially in rare diseases.

Securing market access requires showing a drug to be safe, efficacious and cost-effective when compared to existing drugs for the disease in question.

Orphan drug access challenges

For orphan drugs, small patient populations mean there may not be sufficient clinical trial data to reach standard definitions of statistical significance, resulting in high levels of uncertainty regarding how effective a drug actually is. This, along with high prices, means that proving an orphan drug to be cost-effective is a difficult task.

Of course, lower quality clinical evidence does not equate to lower patient need; for many rare diseases, there are no approved treatment options despite high clinical burden. Some countries have recognised the unique challenges orphan drugs face by introducing specialised processes, such as the NICE highly specialised technology process in England or adapting their existing processes. Typically, these result in increased rates of positive recommendations for orphan drugs.

Pharmaceutical companies, agencies and
governments must continue to work
towards improving access to orphan drugs.

Orphan drug value demonstration strategies

Unfortunately, several markets still make no allowances for orphan status. Those that do vary significantly in the exact way they go about it. Pharmaceutical companies and the agencies that work with them are therefore forced to pursue novel ways of demonstrating an orphan drug’s value. In the absence of gold-standard randomised controlled trials, which compare a drug to existing (in rare disease, typically off-label) treatments, health economists can use statistical methods to conduct an indirect treatment comparison (ITC).

Alternatively, data from several trials or case studies can be pooled to increase sample sizes, which requires a systematic review of the existing literature on a disease. These reviews, as well as clinician engagement activities such as advisory boards, can provide a more well-rounded view of the existing treatment landscape.

Unified efforts for rare disease treatments

Regardless of the approach chosen, pharmaceutical companies, agencies and governments must continue to work towards improving access to orphan drugs so that patients with rare diseases can access the novel treatments they desperately need.