Rare diseases have become a focal point in the pharmaceutical world ever since the Orphan Drug Act, or ODA, was signed into law a little over 30 years ago. In fact, the ODA catalyzed the development of more than 400 new treatments for rare diseases in the United States alone.
Source: Wikimedia Commons.
The trick has been that the ODA confers a number of significant benefits to drugmakers, such as extended market exclusivity, tax credits, accelerated regulatory reviews, waivers of regulatory fees, and the ability to apply for grants from the Food and Drug Administration and National Institutes of Health to offset development costs.
As a result, the orphan-drug space has absolutely blossomed and is currently on track to grow to a stunning $130 billion market by 2020. Put simply, orphan drugs are now one of the largest and fastest-growing markets within the entire pharmaceutical industry.
What's truly staggering, however, is that we've still barely made a dent in the immense rare-disease landscape. As our understanding of the genetics of disease has improved, we've come to realize that there are literally thousands of extremely rare disorders, many of which have horrifying complications that doctors are simply unable to do much about at present.
With this in mind, here is a look at three "ultra-rare" diseases with no approved treatments -- despite their nightmarish symptoms -- that clearly illustrate the vast unmet medical need for orphan indications in general.
Adult-onset Still's disease
The mascot for ultra-rare Still's disease, which afflicts less than 1 in 1,000,000 adults, is a dragon. Why? Because one of the most common symptoms is a daily fever that often exceeds 104 degrees F, making your body feel as if it's on fire.
Still's disease is believed to be an extreme form of arthritis. It was first described in children but is now known to occur in adults, although on a far less frequent basis. The disease is characterized by high fevers, salmon-colored rashes, and extreme inflammation in the joints.
Source: www.stillsdisease.org.
Fortunately, some of the biological-based drugs indicated for rheumatoid arthritis, such as Amgen's (AMGN +3.26%) Enbrel and Johnson & Johnson's (JNJ +0.75%) Remicade, do provide symptom relief in a decent portion of patients. Nevertheless, there are no truly disease-modifying treatments available, meaning that those afflicted with Still's remain locked in a lifelong struggle to control their devastating symptoms.
Berlin breakage syndrome
Berlin breakage syndrome, or Nijmegen breakage syndrome, is an extremely rare autosomal recessive syndrome characterized by an abnormally small head, short stature, a poor immune system, and, worst of all, a predisposition to blood-based cancers. Studies have shown that about 40% of Berlin breakage patients end up developing some form of fatal blood-based disorder.
Source: Creative Commons.
Because Berlin breakage patients also have a compromised immune system, they are prone to respiratory infections that are frequently fatal.
On the treatment front, there's little that can be done for these patients, aside from being monitored by an immunologist and an oncologist. However, the disease does appear amenable to a gene-therapy approach that would correct the mutation in the underlying NBN gene that's responsible for the syndrome.
Fatal familial insomnia
Can't sleep? Perhaps you have what is known as fatal familial insomnia -- a super-rare genetically based disease that's known to affect only 25 families in the entire world. This fatal sleep disorder is caused by a mutated protein in the brain that makes it impossible for people to sleep. In fact, sleep aids actually make the condition worse.
Source: Flickr user Alyssa L. Miller.
The odd part is that it tends to manifest later in life. So a person wakes up one day and then never sleeps again. Death comes about a year and a half later.
Although vitamin therapy and sensory deprivation have helped in some cases, the disease is always fatal, and an effective treatment remains elusive.
Key takeaways
The pharmaceutical industry has made great strides in advancing important new treatments for dozens of rare and ultra-rare diseases over the past three decades. BioMarin (BMRN +0.87%), for instance, has successfully brought five products to market for rare diseases, such as Aldurazyme for the life-threatening lysosomal disorder mucopolysaccharidosis I. And the company now has an experimental treatment, drisapersen, under regulatory review for Duchenne muscular dystrophy.
Nevertheless,the scope of the problem, as these examples illustrate, is astounding. Pfizer's (PFE +1.77%) Dr. Brenda Cooperstone perhaps summed up the problem best at the World Orphan Drug Congress in 2013, stating that it could take hundreds of years to tackle the scourge of rare diseases at our current rate of innovation.
To speed up the process of discovery and drug development, pharma companies far and wide have been teaming up to collaborate on a diversity of rare conditions. For example, Celgene Corp. (CELG +0.00%) joined forces with the rare disease specialist Acceleron Pharma (XLRN +0.00%) recently to develop luspatercept as a potential treatment for two rare blood diseases, namely beta-thalassemia and myelodysplastic syndromes.
But the sheer size of the unmet medical need in this area is so monstrous that new, innovative solutions will need to be brought to bear before we see any significant progress.
