Most rare diseases have no FDA-approved treatment, but legitimate rare disease treatment options still exist. Doctors can prescribe approved drugs off-label, patients can search ClinicalTrials.gov, and physicians can seek investigational drugs through FDA expanded access or the federal Right to Try Act. With a prescription, compounding pharmacies can prepare discontinued drugs or forms and strengths not sold commercially. Compounded drugs are not FDA-approved, so every decision belongs with a knowledgeable prescriber.
An estimated 95% of rare diseases have no FDA-approved treatment, according to the National Center for Advancing Translational Sciences (NCATS). About 10,000 rare diseases together affect roughly 30 million Americans, nearly 10% of the population. Understanding the full range of rare disease treatment options matters, because “no approved drug” is not the same as “nothing can be done.”
This article is a map, not a promise. It explains why the gap exists, how each path works, where compounded medications fit (and where they do not), and how to build a plan with your care team. Every path runs through a physician, and none comes with guarantees.
The Treatment Gap: Why Most Rare Diseases Have No Approved Drug
In the United States, a rare disease is one that affects fewer than 200,000 people. Because each patient group is small and often scattered, developing and testing a new drug is hard to fund and hard to study, which is why most rare diseases still lack an approved treatment.
The FDA’s rare disease page estimates that more than 30 million Americans, about 1 in 10, live with one of these conditions. NCATS reports that of the more than 10,000 known rare diseases, only a few hundred have safe, effective treatments.
How the Orphan Drug Act Changed the Picture, and What It Didn’t Fix
Congress passed the Orphan Drug Act in 1983 to encourage drug development for small patient populations. According to the FDA, it offers tax credits for clinical testing, waivers of certain user fees, and up to seven years of market exclusivity.
A StatPearls review of orphan drug laws notes that only about ten drugs for orphan diseases were available before 1983, and by 2015 the FDA had approved more than 550 orphan drugs and granted over 3,600 orphan designations. Even so, with roughly 10,000 rare diseases and effective treatments for only a few hundred, thousands of conditions still have none.
The story of cysteamine eye drops shows how long the road can be. Cystinosis affects about 600 children and young adults in the U.S. and can cause crystals to build up in the cornea. As the National Human Genome Research Institute recounts, patients received experimental drops through a National Eye Institute study beginning in 1986, and the FDA approved the product, Cystaran, on October 3, 2012. That is 26 years of access through research before approval.
Off-Label Prescribing: Using Approved Drugs in New Ways
Off-label use means a doctor prescribes an FDA-approved drug for a disease, dose, or route that is not on its label. It is legal and can be medically appropriate, especially when no approved treatment exists, but the FDA has not determined that the drug is safe and effective for that specific use.
The FDA’s patient guide to off-label use encourages patients to ask what evidence supports the choice, what the risks and benefits are, and whether a clinical trial might be an option. Insurance may not cover a drug used off-label, so it helps to ask about coverage before starting.
Off-label prescriptions sometimes run into a different problem: the drug exists, but not in the strength or form a patient needs.
Clinical Trials, Expanded Access, and the Right to Try
When no approved or off-label option fits, investigational drugs may be reachable in three ways: joining a clinical trial, a physician requesting FDA expanded access, or the federal Right to Try Act. Each path needs a physician’s involvement, and in every case the drug company must be willing to provide the drug.
Clinical Trials and ClinicalTrials.gov
ClinicalTrials.gov, a database from the National Institutes of Health, lets patients and doctors search studies by condition and location. The Genetic and Rare Diseases Information Center (GARD) offers free help from information specialists who can point you toward experts and trials.
Expanded Access (Compassionate Use)
Expanded access, often called compassionate use, lets a patient receive an investigational drug outside a trial. Under the FDA’s process for physicians, the doctor secures the manufacturer’s agreement, submits Form FDA 3926, and obtains ethics board approval and the patient’s informed consent. Emergency requests can even be authorized by phone.
The FDA allows more than 99% of the single-patient requests it receives to proceed, but those requests already have a manufacturer’s agreement, so the company’s decision is often the real hurdle.
The Right to Try Act
The federal Right to Try Act, enacted in 2018, offers another route. According to the FDA’s Right to Try page, it applies to patients with a life-threatening disease who have exhausted approved options, cannot join a trial, and give written informed consent. The drug must have completed Phase 1 testing and remain in active development.
The FDA does not review these requests, and manufacturers are not required to provide the drug. Rare diseases that are serious but not life-threatening may not qualify, and no pathway guarantees access or benefit.
Where Compounding Fits in Rare Disease Treatment Options
Compounding cannot create a cure that does not exist. What it can do, with a prescription, is prepare a medication that has been discontinued, is in shortage, or is not made in the strength, form, or allergen-free version a particular patient needs.
Discontinued Drugs and Unavailable Forms
Our page on how compounding works explains how a pharmacist can prepare a medication for an individual patient when a needed drug is in shortage or discontinued altogether.
Under FDA guidance for 503A pharmacies, a drug that is discontinued and no longer marketed, or on the FDA drug shortage list, is not considered commercially available. When a commercial product does exist, the prescriber can document a significant difference for the patient, such as needing a liquid form or avoiding a dye allergy.
“No approved drug rarely means no options; it means the right questions matter more.”
Orphan Formulations in Practice
A 2018 review in the Orphanet Journal of Rare Diseases, written from a European perspective, described compounded preparations for rare diseases such as cysteamine eye drops, 3,4-diaminopyridine capsules, and sildenafil oral liquid for children with pulmonary hypertension.
Several of those medicines later gained approved versions. The eye drops became Cystaran, and 3,4-diaminopyridine, known as amifampridine, was approved by the FDA as Firdapse in November 2018 as the first treatment for Lambert-Eaton myasthenic syndrome. Once an approved product is on the market, compounding a copy is restricted unless a prescriber documents a significant difference, so these examples show compounding as a bridge rather than a permanent substitute.
The Honest Limits
The FDA states that compounded drugs are not FDA-approved, which means the agency does not verify their safety, effectiveness, or quality before they are marketed. The Orphanet authors likewise noted that compounded medications lack randomized trial evidence for quality, safety, and efficacy and called for standardized formulations.
That is why compounding always starts with a prescription and a physician’s judgment. A compounding pharmacist works alongside your doctor, never in place of one.
Complex Conditions, Sensitive Patients, and the Role of a Specialty Pharmacy
Rare diseases are not the only place standard medications fall short. Many people with complex or hard-to-treat conditions face similar access problems: no form they can tolerate, a reaction to fillers or dyes, or a need for a strength no manufacturer makes.
As a functional medicine pharmacy in Irvine, King’s Pharmacy and Compounding Center prepares compounded medications for mast cell activation syndrome (MCAS), such as ketotifen and cromolyn sodium, as capsules, liquids, or topicals that can leave out gluten, soy, dyes, preservatives, and sugars.
Our Lyme disease medication support includes custom-dosed antibiotics for children and adults, along with liquid, topical, or other non-pill forms for patients who have trouble swallowing. Each preparation requires a prescription and is made for one patient.
Prescribers facing a discontinued drug or an unavailable form can find resources for prescribers and talk directly with our pharmacists about whether a formulation is possible.
Next Steps: Exploring Rare Disease Treatment Options With Your Care Team
A strong plan usually starts with a specialist or rare disease center. From there, ask about the evidence for off-label options, look for active trials, connect with a patient advocacy group, and, if a medication exists but not in a form you can use, ask whether a compounding pharmacist can help.
Useful questions include whether you qualify for trials on ClinicalTrials.gov, whether a manufacturer offers expanded access, and how insurance would handle each choice.
Outside the clinic, GARD’s information specialists, the National Organization for Rare Disorders (NORD), and disease-specific advocacy groups can help you find experts. Keep a written record of every medication you have tried and how you responded, so each new doctor can see the full picture.
The Gap Is Real, and So Are the Options
When NCATS estimates that 95% of rare diseases lack an FDA-approved treatment, it describes a real gap, but the map of rare disease treatment options is bigger than it looks. Off-label use, trials, expanded access, and the right to try all run through a prescriber. Compounding is one more tool, best suited to discontinued drugs, unavailable strengths or forms, and patients who cannot tolerate commercial ingredients.
Have questions about whether a compounded medication is right for you? Talk to your prescribing physician, then connect with the pharmacists at King’s Pharmacy and Compounding Center in Irvine, CA, to get started.
Request a Refill or Contact King’s Pharmacy at 949.387.0780.
Medical disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice. Compounded medications require a valid prescription, and treatment decisions should always be made with your physician.
Frequently Asked Questions
What are my options if there is no FDA-approved treatment for my condition?
Rare disease treatment options can include an approved drug used off-label, a clinical trial, or an investigational drug requested through FDA expanded access or the Right to Try Act. If a needed medication is discontinued or not made in a form you can use, a compounding pharmacy may be able to prepare it with a prescription.
What is the difference between expanded access and the Right to Try Act?
With expanded access, a physician submits a request to the FDA, and treatment requires ethics board approval and informed consent. The Right to Try Act, enacted in 2018, does not involve FDA review but applies only to patients with life-threatening diseases who have exhausted approved options and cannot join a trial. In both cases, the manufacturer must agree to provide the drug.
Is off-label prescribing legal and safe?
Off-label prescribing is legal, and the FDA recognizes it can be medically appropriate, especially when no approved treatment exists. However, the FDA has not determined that the drug is safe and effective for that specific use. Ask your doctor about the evidence, the risks and benefits, and whether insurance will cover it.
Can a compounding pharmacy make a medication that has been discontinued?
In some cases, yes. Under FDA guidance, a drug that has been discontinued and is no longer marketed is not considered commercially available, so a 503A compounding pharmacy may be able to prepare it with a valid prescription. Your prescriber and pharmacist can confirm whether a specific medication can be compounded.
Are compounded medications FDA-approved?
No. The FDA states that compounded drugs are not FDA-approved, which means it does not verify their safety, effectiveness, or quality before they are marketed. Compounded medications require a prescription and are prepared for individual patients.
