Neglected by the pharmaceutical industry before the Orphan Drug Act of 1983, rare diseases are now front and center in pharma R&D. Approximately one-third of all new medicines approved by the FDA in the past 5 years were developed for the treatment of diseases that affect fewer than 200,000 Americans. Now, however, the increasing number and cost of orphan drugs are a growing concern to patients, providers and payers. The specter of ballooning drug costs should not, however, discredit the original purpose of the Orphan Drug Act: to encourage the development of new treatments for patients with rare diseases who had no hope of a cure or even symptomatic relief. 

 

A case in point is atypical hemolytic uremic syndrome (aHUS), a rare, life-threatening disease with an incidence of only 2 per million in the U.S. and 1.5-1.8 per million in Europe. When Danielle Williams was told that her son Justice, a previously growing and healthy boy, had aHUS, she was scared. She had never heard of aHUS before and didn’t know what, if any, treatments were available. It turns out that she had good reason for concern.

 

Had Justice been diagnosed just a year earlier, his options would have been very limited. Standard treatment was plasma exchange or infusion, which produced dismal results: within a year of diagnosis, 65% of all aHUS patients treated with plasma exchange or infusion died, required dialysis, or had permanent renal damage. Fortunately for the Williams family, and all the other patients with aHUS, Alexion Pharmaceuticals Inc., Cheshire, Conn., had developed a treatment for this devastating disease. The product of this commitment, a monoclonal antibody called Soliris, gave Justice a chance. Its availability was a “miracle,” said Williams.

 

But critics have been quick to point out that companies who develop orphan drugs may not purely be motivated by altruism. After all, there is a lot of money to be made in the rare disease space. Wall Street analysts estimate that at a cost of $400,000 per patient per year, Soliris could bring Alexion $2.6 billion in annual sales by 2017.

 

 

When asked to explain the cost of orphan drugs, Martin Mackay, EVP, Global Head of R&D, Alexion, said that companies developing these drugs “continue to invest in R&D programs to develop more innovative treatments for patients suffering with other severe and rare diseases. Additionally, we invest a great deal in disease education and other programs to ensure that patients with these devastating diseases receive optimal care. There are also several unique challenges when working in the rare disease setting, which are reflected in the cost.” 

 

Mackay sites the design of clinical trials as one such challenge, explaining that these trials are often without precedent, so there are no roadmaps to follow for the endpoints. Companies developing treatments for rare diseases have to fill this void. They are often pioneers in the assessment of the efficacy and safety of orphan drugs and must work closely with regulatory bodies around the world to ensure consensus. 

 

Patient recruitment in rare diseases is tough as well. Due to the small patient populations and challenges with diagnosis, patient recruitment requires a large and vast global network to enroll very small numbers of patients, explains Mackay.

 

As well, rare diseases are often poorly studied, and the pathophysiology of the disease is not well understood. This can make the search for the defect difficult, prolonged, and therefore costly. 

 

Despite these challenges, says Mackay, “We are driven to pursue therapeutic candidates that bring significant value to patients suffering with devastating diseases rather than incremental benefits. We aim to develop and deliver treatments that will dramatically transform their lives.”

 

 

Nobody can deny that orphan drugs can be profitable, and some question whether the costs are excessive. But many also maintain that providing desperately needed treatments for rare diseases is the right thing to do, despite the cost…that turning our backs on patients with rare diseases and their families, especially after the success of orphan drug incentives, is unethical. As more orphan drugs become available, the trick will be to ensure that the ethical obligation to treat patients with rare diseases is balanced by sustainable costs.