Treatments for rare diseases can vary from FDA-approved orphan drugs to diet and lifestyle changes to surgical intervention—or all of these choices.
To date, there are 600+ orphan drugs approved for rare diseases, and many conditions have multiple orphan drugs indicated for their treatment (see Appendix A). Quite a few of these orphan drugs also treat rare cancers.
In addition to the approved orphan drugs, many patients with rare conditions are prescribed medications for off-label uses to treat their symptoms. The research behind these drugs varies greatly, and clinicians are strongly encouraged to seek advice from leading experts of a given rare disease before prescribing any off-label medication.
Many patients with rare diseases require a restricted diet or other lifestyle change to manage their condition. For example:
Phenylketonuria is an inherited disorder that causes toxic levels of phenylalanine and may be managed with a phenylalanine-restricted diet in some patients (who may also benefit from the orphan drug Kuvan [sapropterin]).
Ménière’s disease is an abnormality of the inner ear that leads to vertigo and dizziness. In most cases, a restrictive diet (no salt) plus the possible use of antihistamines and/or diuretics are used to manage the condition.
Xeroderma pigmentosa is an inherited condition in which persons are extremely sensitivity to ultraviolet sunlight. It is managed by avoiding direct exposure to the sun and using sunscreen.
Surgery is another primary treatment option. For example, a patient with tetralogy of Fallot, a congenital heart defect, can be treated with open heart surgery, while a child with craniosynostosis can often lead a normal life following neurosurgery and plastic surgery if addressed early on in life.
Treatment vs Cure
Treatment options can be grouped into 3 categories:
Curative Treatmentsare uncommon for rare diseases and include treatment for most rare infections (eg, Tropheryma whipplei) or rare poisonings (eg, snakebites or cyanide). Surgery can also treat many anatomical defects, such as craniosynostosis or coarctation of the aorta.
Disease-Modifying Treatments may receive orphan drug approval to treat rare diseases. For example, enzyme replacement therapy (ERT) is approved for use in patients with Gaucher disease to possibly delay or stop the progression of the disease, although the disease is still present. In many cases, patients can lead normal lives following treatment even though the underlying disease is still present. For others, the treatment may delay disease progression but will not stop it.
Symptom-Modifying Treatmentmay or may not include approved orphan drugs, but it is necessary to treat the plethora of symptoms that result from a rare disease (eg, pain, nausea, gastrointestinal problems, anemia). A possible concerns associated with treating symptoms is that they may not be covered by insurance, and this can lead to major financial setbacks for a family—especially if surgery, complicated medical/communication devices, and/or physical therapy are necessary.
Long-Term Effects of Treatment
A new concern for many in the rare disease community comprises the long-term effects of treatment. Until the passing of the Orphan Drug Act, there were very few, if any, treatments for rare conditions. However, as orphan drugs have become available, patients who would otherwise not have lived very long are able to lead lengthy, productive lives. There are numerous natural history studies on the how a disease progresses without treatment, but now the rare disease community needs new studies to determine how patients will live and for how long and with what new adverse effects, following the administration of life-saving medications. For example children with early-onset or infantile Pompe disease seldom lived past their second or third birthday before an ERT was made available to them. Now, they are living much longer.
Earlier this year, Megan Crowley, a student at Notre Dame and a patient with infantile Pompe disease, was a special guest of President Trump’s first speech before the Senate and Congress. She remains severely disabled and requires constant assistance, but she is taking ERT and leading a full life.
It is not known how long ERT will be effective or what other organs may be impacted by the disease and the treatment over time. These lifesaving medications have created a new population of patients who need to be studied. Many patients with rare diseases are encouraged to enroll in patient registries and/or natural history studies to help advance the medical community’s understanding of each rare disease case.
As treatments for rare diseases have improved, many diseases have not remained death sentences. They have become chronic conditions.