Orphan Drug Designation is one of the most important ways for new mesothelioma treatments to reach patients. This special designation is granted by the U.S. Food and Drug Administration to drugs that show promise in treating rare diseases. The Orphan Drug Designation offers pharmaceutical companies valuable incentives to invest in research for rare conditions like mesothelioma, which might otherwise be overlooked due to small patient populations and limited financial benefit.
History of the Orphan Drug Designation
In 1983, the United States Congress passed the Orphan Drug Act (ODA), a law that provided incentives to pharmaceutical companies to develop drugs aimed specifically at treating rare diseases. These drugs are referred to as “orphan drugs” because earlier development efforts may have been dropped or “orphaned” due to a lack of funding or interest in drug development.[1]
Kevauver Harris Amendment
The law was created in response to a notable change in the way pharmaceutical companies invested in drug development following the 1962 passage of the Kefauver-Harris Amendment, a famous and far-reaching change to the original Federal Food, Drug, and Cosmetic Act. The amendment was crafted in response to the tragic result of the use of the drug thalidomide in the 1950s.[2]
Thalidomide is a drug that was originally developed as a sedative; it was also frequently used to treat morning sickness in pregnant women, which led to severe birth defects in those women’s infants, including limb malformations. The Kevauver-Harris amendment gave the Food and Drug Administration (FDA) the authority to require proof of both effectiveness and safety before approving a new drug.
This shift led to our current system, which requires phased clinical trials before a drug can be introduced to the market. It also significantly increased the cost of drug development. As a result, the pharmaceutical industry redirected its focus, attention, and investment to developing drugs that would be used for larger populations and that would generate more profits. Research into treatments for rare diseases like mesothelioma came to a virtual stop.[2]
The Orphan Drug Act
The Orphan Drug Act originally defined a rare disease as one that “occurs so infrequently in the United States that there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from the sales in the United States of such drug.” In 1984 it was revamped to define a rare disease as one affecting “less than 200,000 persons in the United States” or more than 200,000 persons, but for whom “there is no reasonable expectation that the cost of developing and making available in the United States a drug for such disease or condition will be recovered from the sale in the United States.”[2]
How Does a Drug Get Approved for Orphan Drug Designation?
To obtain orphan drug designation (ODD) in the United States, drug manufacturers apply to the FDA’s Office of Orphan Products Development. The application can be submitted at any point during the drug’s development, even before clinical trials begin, but there must be sufficient scientific rationale and preliminary data to support the application. Though this is often a challenge, early designation offers significant benefits, as the incentives connected to ODD exist throughout the development process.
Establishing the Disease as Rare
The application needs to include documentation from multiple sources, including medical literature, patient registries, and health databases, showing that the drug’s target disease meets the rare disease criteria. It also needs to include a detailed scientific justification for why their drug candidate is appropriate for treating the rare disease. This includes preclinical data, mechanism of action studies, and any available clinical evidence. The application should establish that the drug offers a potential therapeutic benefit for the target condition.
Establishing the Unmet Medical Need of the Disease
The submission must also establish that there is a significant unmet medical need for the rare disease. This involves documenting the current standard of care, existing treatment options, and their limitations. Companies must show how their drug could address the gaps in current therapy or provide better treatment outcomes.
Establishing the Financial Need
In addition to providing medical and scientific support for their application, a drug company seeking orphan drug designation needs to show that it can’t reasonably expect to recover its development costs without orphan drug incentives. This requires detailed financial projections, market analysis, and cost-benefit calculations. Companies need to establish that the small patient population and high development costs make recovering costs nearly impossible without the ODD’s additional support.
The FDA Review Process
Upon receiving an application, it typically takes the FDA about 90 days to go through its review process, evaluating all the materials that have been submitted. This review often involves the agency requesting additional information or clarification from the drug company before either granting or denying the application. If granted, the designation applies specifically to the drug for the particular rare disease indication. If denied, companies can appeal the decision or resubmit with additional supporting data.[1]
Maintaining Orphan Drug Designation
To maintain an orphan drug designation for a medication, drug companies need to continue meeting eligibility requirements throughout the drug’s development. If the disease becomes more prevalent or if multiple effective treatments become available, the designation may be reassessed and revoked.
Manufacturers also need to submit annual reports on their development progress and any changes in the drug’s development status or the target disease epidemiology. They are also required to complete the same clinical trials that other drugs do to demonstrate safety and efficacy, though the FDA may accept smaller clinical studies or alternative endpoints given the rarity of the disease and the small patient population.
Benefits of Orphan Drug Designation
Companies whose drugs are awarded orphan drug designation receive many benefits, including:[1]
- Financial benefits, including tax credits for clinical research expenses (up to 25% in the United States), reduced or waived regulatory fees, and potential grants for clinical development. These incentives help offset the high costs of drug development for small patient populations.
- Market exclusivity for seven years, during which no competing generic or similar drug can be approved for the same indication. This provides companies with protected market access to earn their investment back.
- Regulatory support, including more frequent meetings with the FDA’s regulatory staff, guidance on trial design, and potentially expedited review processes. This can significantly streamline the path to market approval.
Why Do Mesothelioma Treatments Qualify for Orphan Drug Status?
In the United States, mesothelioma is newly diagnosed in approximately 3,000 people each year. This qualifies it as a rare disease, with an extremely small patient population. Without the incentives offered by orphan drug designation, pharmaceutical companies would face significant challenges in moving forward with drug development. These challenges include:
- The small patient population makes it impossible to conduct the large-scale clinical trials typically required for drug approval.
- High development costs combined with small market potential create financial barriers for pharmaceutical investment.
- Mesothelioma’s complex biology requires extensive research and expertise that may not be as available for more common cancers.
How Orphan Drug Designation Has Impacted Treatment for Mesothelioma
Mesothelioma is an extremely challenging disease to treat. It has proven resistant to traditional cancer treatments and continues to be considered a terminal illness. Still, orphan drug designation has facilitated the introduction of some of the most promising mesothelioma treatments, including:
- Pemetrexed: Pemetrexed received orphan drug status in 2001 and gained FDA approval for treating pleural mesothelioma in 2004. Combining it with cisplatin is one of the most common and effective chemotherapy regimens for mesothelioma patients.
- Opdivo and Yervoy: The combination of Opdivo (nivolumab) and Yervoy (ipilimumab) represents the first and only FDA-approved immunotherapy for mesothelioma. This drug combination received orphan designation for mesothelioma treatment in 2017 and gained full approval in 2020.
Recent Orphan Drug Designations for Mesothelioma
The FDA continues to grant orphan drug designation to promising new mesothelioma treatments, including the following:
SynKIR-110 CAR T-Cell Therapy
The FDA recently granted orphan drug status to SynKIR-110, a novel CAR T-cell therapy specifically designed for mesothelioma treatment. This cutting-edge approach represents a new frontier in personalized cancer treatment.
IK-930 Fast Track Designation
IK-930 from Ikena Oncology received both orphan drug designation and Fast Track designation, which provides expedited FDA review. The medication’s approval came for its use in pleural mesothelioma patients who are deficient in a specific tumor suppressor gene, allowing their cancer to progress and mutate more rapidly. This deficiency is present in roughly 40% of mesothelioma patients. The IK-930 drug targets the pathway associated with tumor growth in these patients.
ISM6331 Pan-TEAD Inhibitor
In August 2024, the FDA granted ISM6331 orphan drug designation. This innovative therapeutic agent is a small-molecule inhibitor that targets a specific protein family known to play a key role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. The orphan drug designation came after the FDA was presented with proof that the drug had provided a broad anti-tumor effect in the lab and in animal studies.
MVdeltaC
In June 2025, the FDA granted orphan drug designation to MVdeltaC, a treatment for pleural mesothelioma that relies on a modified form of the measles virus that replicates within tumor cells, induces cell death, and reactivates the body’s response within tumors that have become invisible to the immune system.
ONCOFID-P
Italian manufacturer Fidia Farmaceutici received orphan drug designation for ONCOFID-P in July 2021. This anticancer drug combines the drug paclitaxel with hyaluronic acid, allowing it to bind to specific mesothelioma cells to increase the concentration of the cancer drug within mesothelioma cells, boosting its effectiveness.
The Future of Orphan Drugs in Mesothelioma Treatment
The FDA continues granting orphan drug designations for mesothelioma treatments, and this suggests that researchers continue to believe that better outcomes for mesothelioma patients are possible. The financial incentives provided by orphan status help spur pharmaceutical companies’ interest in developing treatments for the small but deserving patient population that has been afflicted by exposure to asbestos and the negligence of asbestos companies.
As understanding of mesothelioma’s development and molecular biology improves and new therapeutic approaches emerge, orphan drug designation is likely to continue playing an essential role in bringing innovative treatments to patients who desperately need them.
How to Access Orphan Drug Treatments
If you or someone you love has been diagnosed with mesothelioma and you’re interested in accessing orphan drug treatments, there are several options and resources available to you:
- Specialty cancer treatment centers are often involved in the clinical trials that follow orphan drug designation. These facilities both have access to the newest state-of-the-art treatments and may offer the ability to be treated with orphan drugs as part of standard care.
- The National Cancer Institute’s online platform includes a comprehensive database of ongoing studies exploring innovative mesothelioma therapies as well as a clinical trial search platform where you can look up specific information such as participant criteria and sites where research is being conducted.
- The Center for Information and Study on Clinical Research Participation (CISCRP) is an organization that can help you identify suitable clinical studies.
- Patient advocacy groups can provide you with information about available treatments and how to access them.
The Importance of Continued Support
The success of orphan drug designation in mesothelioma treatment makes clear the importance of continued support for rare disease research. Patient advocacy, fundraising efforts, and awareness campaigns are all crucial to encouraging researchers to continue their work on this challenging disease, and making patients aware of the existence of orphan drug designation and what it means helps patients, caregivers, and healthcare providers understand all the options available and assist them as they make informed treatment decisions.
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