This week on The CheckRare Brief, we are joined by Eugene Lee, Head of CMI Media Group’s Rare Disease Division, for an industry perspective on some of the biggest developments in rare disease.

New Rare Disease Center of Excellence

CMI Media Group recently launched a Specialized Rare Disease Center of Excellence to scale precision marketing to smaller pharmaceutical companies.  CMI is well known for its media and communications capabilities in the healthcare space for 37 years. CMI is now applying this longstanding commitment to the healthcare industry to rare conditions, which require a more targeted approach because patient populations and HCP audiences are smaller and highly specialized. CMI’s Centers of Excellence (COE) bring together CMI's data, technology, expertise, and experience to help clients navigate that complexity. 

The FDA approved Bravnesta (lutetium Lu 177 dotatate) to treat neuroendocrine disorders. 

The approval is for a generic version of Novartis’ radioligand therapy, Lutathera, to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The approval is largely based on showing the new generic drug, Bravnesta, has similar bioequivalence and therapeutic equivalence.  

Novartis’ therapy has been available since 2018 and, in that time, has provided great benefit to these patients, and those patients now have a generic option to assist them.

The FDA also approved Lyrfigtu (lirafugratinib) as second-line therapy for patients with cholangiocarcinoma.  

Cholangiocarcinoma is an aggressive cancer of the bile duct. Standard first-line therapy for the past 10 years has been gemcitabine and cisplatin, a chemotherapy combination used for many types of cancers. If that treatment is no longer effective, Lyrfigtu is an option. 

Lyrfigtu is a FGFR2 inhibitor, and FGFR2 is a protein often altered in cancers. The drug is also being tested for other solid tumors with FGFR2 fusions. The data supporting approval came from a phase 1/2 study in which median progression-free survival was 11 months.  Which, for this aggressive cancer, is very significant.

Second-line therapies, especially for rare cancers, are a common initial indication for new orphan drugs. First-line treatments are often well established, as is the case here, so replacing them requires a strong body of evidence. 

Finally, the FDA issued new guidelines for clinical trials involving rare diseases, and other diseases with diverse patient populations.

The new initiative is a statistical model that accounts for different symptoms and presentations in patients with the same disease. For example, in Fabry disease, some have poor kidney function, others have cardiac problems, others have neuropathic pain. To have a clinical trial that only include one of those symptoms as the baseline outcome measure, limits the patients who can enrol.

The new FDA model allows patients to enroll with different baseline levels for different outcome measures and subgroup them accordingly, but the final analysis combines those subgroups into a total group to see whether the drug is effective, statistically speaking.  It can also reduce the recruitment time for these small rare conditions from several years to several months. 

The rare disease space is known for its innovative research and it is nice to see that innovation also occurring at the regulatory level. 

Looking ahead

Several important FDA decisions are coming up, including:.

Elevar Therapeutics' therapy for cholangiocarcinoma and Praxis' therapy for SCN2A and SCN8A deficiencies.
Egetis Therapeutics' orphan drug to treat patients with  MCT8 deficiency.




References

CMI Media Group Launches Specialized Rare Disease Center of Excellence (COE) to Scale Precision Marketing for Niche Pharma

https://cmimediagroup.com/resources/cmi-media-group-launches-specialized-rare-disease-center-of-excellence-coe-to-scale-precision-marketing-for-niche-pharma/

FDA approves Lu177 dotatate for NETs

https://www.globenewswire.com/news-release/2026/09/22/3366274/0/en/lantheus-receives-final-fda-approval-for-bravnetsa-lutetium-lu-177-dotatate-the-only-radiopharmaceutical-fda-has-determined-to-be-bioequivalent-and-therapeutically-equivalent-to-lu.html 

FDA approves drug for 2nd line cholangiocarcinoma

https://www.globenewswire.com//news-release/2026/09/23/3367897/0/en/elevar-therapeutics-announces-fda-approval-of-lyrfigtu-lirafugratinib-as-second-line-cholangiocarcinoma-with-fgfr2-fusion-or-other-rearrangement-treatment-option.html

FDA Provides novel ways to design clinical trials for rare diseases while still be statistically compliant

https://www.fda.gov/drugs/regulatory-science-action/novel-stratum-specific-trial-design-improves-statistical-power-rare-diseases-heterogenous-clinical

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This week on The CheckRare Brief, we are joined by Eugene Lee, Head of CMI Media Group’s Rare Disease Division, for an industry perspective on some of the biggest developments in rare disease.

CMI Media Group recently launched a Specialized Rare Disease Center of Excellence to scale precision marketing to smaller pharmaceutical companies.  CMI is well known for its media and communications capabilities in the healthcare space for 37 years. CMI is now applying this longstanding commitment to the healthcare industry to rare conditions, which require a more targeted approach because patient populations and HCP audiences are smaller and highly specialized. CMI’s Centers of Excellence (COE) bring together CMI's data, technology, expertise, and experience to help clients navigate that complexity. 

The FDA approved Bravnesta (lutetium Lu 177 dotatate) to treat neuroendocrine disorders. 
The approval is for a generic version of Novartis’ radioligand therapy, Lutathera, to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The approval is largely based on showing the new generic drug, Bravnesta, has similar bioequivalence and therapeutic equivalence.  

Novartis’ therapy has been available since 2018 and, in that time, has provided great benefit to these patients, and those patients now have a generic option to assist them.
The FDA also approved Lyrfigtu (lirafugratinib) as second-line therapy for patients with cholangiocarcinoma.  

Cholangiocarcinoma is an aggressive cancer of the bile duct. Standard first-line therapy for the past 10 years has been gemcitabine and cisplatin, a chemotherapy combination used for many types of cancers. If that treatment is no longer effective, Lyrfigtu is an option. 

Lyrfigtu is a FGFR2 inhibitor, and FGFR2 is a protein often altered in cancers. The drug is also being tested for other solid tumors with FGFR2 fusions. The data supporting approval came from a phase 1/2 study in which median progression-free survival was 11 months.  Which, for this aggressive cancer, is very significant.

Second-line therapies, especially for rare cancers, are a common initial indication for new orphan drugs. First-line treatments are often well established, as is the case here, so replacing them requires a strong body of evidence. 

Finally, the FDA issued new guidelines for clinical trials involving rare diseases, and other diseases with diverse patient populations. 

The new initiative is a statistical model that accounts for different symptoms and presentations in patients with the same disease. For example, in Fabry disease, some have poor kidney function, others have cardiac problems, others have neuropathic pain. To have a clinical trial that only includes one of those symptoms as the baseline outcome measure, limits the patients who can enrol.

The new FDA model allows patients to enroll with different baseline levels for different outcome measures and subgroup them accordingly, but the final analysis combines those subgroups into a total group to see whether the drug is effective, statistically speaking.  It can also reduce the recruitment time for these small rare conditions from several years to several months. 

The rare disease space is known for its innovative research and it is nice to see that innovation also occurring at the regulatory level. 

Looking ahead
Several important FDA decisions are coming up, including:.
Tlevar Therapeutics' therapy for cholangiocarcinoma and Praxis' therapy for SCN2A and SCN8A deficiencies.
Egetis Therapeutics' orphan drug to treat patients with  MCT8 deficiency.

References
CMI Media Group Launches Specialized Rare Disease Center of Excellence (COE) to Scale Precision Marketing for Niche Pharma
https://cmimediagroup.com/resources/cmi-media-group-launches-specialized-rare-disease-center-of-excellence-coe-to-scale-precision-marketing-for-niche-pharma/

FDA approves Lu177 dotatate for NETs
https://www.globenewswire.com/news-release/2026/09/22/3366274/0/en/lantheus-receives-final-fda-approval-for-bravnetsa-lutetium-lu-177-dotatate-the-only-radiopharmaceutical-fda-has-determined-to-be-bioequivalent-and-therapeutically-equivalent-to-lu.html 

FDA approves drug for 2nd line cholangiocarcinoma
https://www.globenewswire.com//news-release/2026/09/23/3367897/0/en/elevar-therapeutics-announces-fda-approval-of-lyrfigtu-lirafugratinib-as-second-line-cholangiocarcinoma-with-fgfr2-fusion-or-other-rearrangement-treatment-option.html

FDA Provides novel ways to design clinical trials for rare diseases while still be statistically compliant
https://www.fda.gov/drugs/regulatory-science-action/novel-stratum-specific-trial-design-improves-statistical-power-rare-diseases-heterogenous-clinical 

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Explore additional CME activities, physician interviews, podcasts, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for the latest rare disease education, expert interviews, an...

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Paz Vellanki, MD, PhD, Vice President of Clinical Development at Precision for Medicine, discusses the FDA CDER’s Accelerating Rare Disease Cures (ARC) Program.

The ARC Program was launched in 2022 with the goal of accelerating the development of safe and effective therapies for patients with high unmet need with rare diseases. The program has included a variety of initiatives, including several successful pilot programs, patient listening sessions, novel clinical trial design workshops, and a focus on patient-centric drug developments.

Dr. Vellanki explains that drug development for rare diseases is often more complex than common diseases, requiring a different approach from conventional trial designs, including the use of novel endpoints and biomarkers. To address these needs, the ARC Program’s initiatives encourage increased engagement between sponsors and the FDA to enhance formal meetings, an aspect that Dr. Vellanki says is important for small biotech companies who face challenges like small patient populations and complex endpoint selection.

Recently, CDER issued a five-year strategic map for the ARC Program, defining what the program was and what stage it is currently in. It analyzes the pilot programs and metrics on success, determining next steps and how to continue efforts across the FDA. Proposed advances focus on strategies to advance scientific and regulatory innovations, expand novel trial tools, and streamline approval pathways for rare disease therapies. Dr. Vellanki notes that many of the ongoing initiatives are focused in specific disease areas, but there is hope for expansion across rare disease categories.

To learn more about rare disease drug development, visit https://checkrare.com/drug-development/

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Amy Waldman, MD, pediatric neurologist and Medical Director of the Leukodystrophy Center at the Children’s Hospital of Philadelphia, discusses the approval of zilganersen to treat patients with Alexander disease.

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Neelam Goyal, MD, and Christyn Edmundson, MD, use case studies involving three different patients suspected of having MuSK Ab+, LRP4 Ab+, and Triple Seronegative Myasthenia Gravis to discuss how they assess those patients, ensure proper diagnosis, and decide which treatment option is most appropriate for the individual patient.

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Karen A. Jones, EdD, President and CEO of wAIHA Warriors, discusses the approval of Imaavy (nipocalimab) and its impact on patients with warm autoimmune hemolytic anemia (wAIHA).

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My name is Dr. Joshua Zeidner, and I’m a Professor of Medicine and Chief of Leukemia Research at the University of North Carolina Lineberger Cancer Center. I’m here today to raise awareness around an active global, phase 3, double-blind trial evaluating a combination regimen for participants with a specific type of acute myeloid leukemia or AML.

Disclaimer: This material is intended for healthcare practitioners only. This use of Revumenib is under investigation and has not been approved by the FDA or any other regulatory agency worldwide. No conclusions of safety or efficacy can be drawn. Patient eligibility criteria apply.

1. Can you describe the REVEAL-Newly Diagnosed NPM1m trial?
The REVEAL-ND NPM1m trial is evaluating whether the addition of revumenib, a menin inhibitor, to standard chemotherapy improves outcomes in newly diagnosed patients with NPM1-mutated AML compared with chemotherapy alone. It is a global, phase 3, double-blind, trial in which participants will be randomized to receive standard intravenous chemotherapy with either oral revumenib or placebo.

2. What is the trial evaluating?
The trial is designed to assess whether this combination improves key clinical outcomes. The dual primary endpoints are event-free survival and measurable residual disease -negative complete response rate in the bone marrow. A key secondary endpoint is overall survival. Other secondary endpoints include overall response rate, complete response rate, composite complete remission, duration of response, safety and tolerability, and patient-reported fatigue.

3. What is the study design?
Participants are randomized 1:1 to receive oral revumenib 270 mg Q12 without a strong CYP3A4 inhibitor or revumenib 160 mg Q12 with a strong CYP3A4 inhibitor or placebo in combination with intensive chemotherapy during Induction and Consolidation followed by Maintenance. Intensive chemotherapy consists of cytarabine and daunorubicin or idarubicin in the Induction Phase and cytarabine alone in the Consolidation Phase. The Maintenance Phase will consist of revumenib or placebo given twice daily as monotherapy. Oral revumenib or placebo administration will continue for up to 2 years from Induction Cycle 1 Day 1. Bone marrow aspirates/biopsies will be collected to assess response. Participants may undergo hematopoietic stem cell transplant after initial induction chemotherapy or after consolidation and may resume maintenance thereafter.

4. Who is eligible for the trial?
Individuals from all backgrounds and communities are welcome to take part in the trial. Participants may be eligible if they have newly diagnosed, previously untreated, centrally confirmed NPM1 mutated AML and are eligible to receive intensive chemotherapy. Adolescents and adults ≥12 years of age are eligible. Participants must have adequate liver, kidney, and cardiac function.
Key exclusions include pregnancy or breastfeeding, active acute promyelocytic leukemia, active central nervous system (CNS) disease, gastrointestinal (GI) disease that affects drug absorption or indigestion, AML with FLT3-ITD mutation with a variant allele frequency of ≥5%, or if FLT3 inhibitor use is indicated.

5. Where is REVEAL-ND NPM1m enrolling?
The trial plans to enroll approximately 468 patients globally. Recruitment is planned across North America, Latin America, Europe, the Middle East, and the Asia-Pacific region.

6. If our viewers have participants who would potentially benefit from participating in the REVEAL-ND trial, how should they inquire about study enrollment?
The study has an Email address for potential participant enrollment: [email protected].

7. How about if a hospital/healthcare organization would like to participate in the REVEAL-ND trial?
The center should contact the study managers, through the same Email address: [email protected].

Use of revumenib in this setting is investigational and is not approved for this use by the FDA or any health authority worldwide.

References:
https://clinicaltrials.gov/study/NCT07211958#study-plan
Stein E, Issa G, Rego E, et al. A Phase 3 Study of Revumenib in Combination With Intensive Chemotherapy in Patients With Newly Diagnosed NPM1-Mutated Acute Myeloid Leukemia (REVEAL- ND NPM1): Trial in Progress. TPS6602 Poster presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL

Disclaimer: This presentation is sponsored by Syndax. The speaker is being compensated by Syndax for his time and participation in this presentation. The information contained herein is intended solely for educational and informational purposes © 2026 Syndax Pharmaceuticals, Inc. All rights reserved. MED-REV-260086 09/2026.

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The FDA announced the approval of Isembyld (apitegromab-mstn) to treat patients 2 yrs and older with spinal muscular atrophy who are currently receiving SMN2-targeted therapy.

SMA is a genetic condition in which patients lose spinal muscle function due to a mutation in the SMN1 gene. There are three therapies for this condition: one is a gene therapy that replaces the SMN1 gene, and the other two, significantly cheaper therapies, increase the activity of a backup gene, SMN2, to increase the missing SMN protein. 

This new drug is an add-on therapy to those two latter therapies that target SMN2. 

It will be interesting to see how payers and physicians decide where this fits, particularly when you're treating a relatively small patient population with very expensive therapies.

There's another interesting piece to this approval. Scholar Rock received a pediatric priority review voucher. These vouchers are intended to encourage companies to develop treatments for children, something that historically has been more difficult because pediatric clinical trials can be challenging to conduct. We're seeing pharmaceutical companies increasingly pursue these opportunities.

The FDA also approved a gene therapy for MPS IIIa, also referred to as Sanfilippo syndrome type A.  
MPS IIIa is a devastating disease. These children start out looking very healthy, but as toxic levels of heparin sulfate accumulates in their cells, these children begin a cognitive and behavioural decline that completely disrupts the family.

The results from the study leading to the approval is impressive. Instead of the typical cognitive decline seen in these children, adding gene therapy stabilized or improved their cognitive abilities.
The therapy is priced at $3.9 million for a single treatment. That's obviously an enormous dollar amount, and payers generally don't like paying that kind of cost upfront, even when a one-time therapy could potentially be less expensive over the long term than years of continuous treatment.

It's also an important moment for Ultragenyx. This is their second FDA approval in the last month, and they've established 25 centers capable of delivering the gene therapy, with plans to expand that to 40.
So this isn't just about getting therapy approved. It's also about building the infrastructure to actually get these therapies to patients.

The FDA's Center for Devices and Radiological Health (CDHR) introduced its Rare Disease Impact Initiative. 
While we tend to focus on drug therapies to manage patients with rare conditions, there are many diseases that rely on medical devices to manage and/or monitor patients. At last count, the FDA listed over 2000 devices that are being used to help people with rare conditions. 
The FDA's Rare Disease Impact Initiative is designed to help medical-device developers work more directly with the FDA as they develop products for rare disease populations.
It's another part of the rare disease ecosystem that we think deserves more attention.

Looking Ahead
Several important FDA decisions are coming up.
September 26: Mirum's therapy for fibrodysplasia ossificans progressiva, or FOP.
September 27: Tlevar Therapeutics' therapy for cholangiocarcinoma and Praxis' therapy for SCN2A and SCN8A deficiencies.
September 28: Egetis Therapeutics' orphan drug to treat patients with  MCT8 deficiency.

References
FDA approves new SMA drug
https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-therapy-target-muscle-loss-spinal-muscular-atrophy

FDA approves gene therapy for MPS IIIA
https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-pediatric-patients-sanfilippo-syndrome-type 

CDRH Rare Disease Impact Initiative
https://www.fda.gov/about-fda/center-devices-and-radiological-health/cdrh-rare-disease-impact-initiative 


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Explore additional CME activities, physician interviews, podcasts, and rare disease resources at CheckRare.com. Subscribe to the CheckRare Podcast Network for the latest rare disease education, expert interviews, and weekly news.

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This week we discuss the FDA's approval of Isembyld for SMA, the approval of a gene therapy for MPS IIIA, and the FDA's Center for Devices and Radiological Health new Rare Disease Impact Initiative.

Approval of Isembyld for Spinal Muscular Atrophy

The FDA announced the approval of Isembyld (apitegromab-mstn) to treat patients 2 yrs and older with spinal muscular atrophy who are currently receiving SMN2-targeted therapy.

SMA is a genetic condition in which patients lose spinal muscle function due to a mutation in the SMN1 gene. There are three therapies for this condition: one is a gene therapy that replaces the SMN1 gene, and the other two, significantly cheaper therapies, increase the activity of a backup gene, SMN2, to increase the missing SMN protein.

This new drug is an add-on therapy to those two latter therapies that target SMN2.

It will be interesting to see how payers and physicians decide where this fits, particularly when you're treating a relatively small patient population with very expensive therapies.

There's another interesting piece to this approval. Scholar Rock received a pediatric priority review voucher. These vouchers are intended to encourage companies to develop treatments for children, something that historically has been more difficult because pediatric clinical trials can be challenging to conduct. We're seeing pharmaceutical companies increasingly pursue these opportunities.

Gene Therapy Approved for MPS IIIA

The FDA also approved a gene therapy for MPS IIIa, also referred to as Sanfilippo syndrome type A.

MPS IIIa is a devastating disease. These children start out looking very healthy, but as toxic levels of heparin sulfate accumulates in their cells, these children begin a cognitive and behavioural decline that completely disrupts the family.

The results from the study leading to the approval is impressive. Instead of the typical cognitive decline seen in these children, adding gene therapy stabilized or improved their cognitive abilities.

The therapy is priced at $3.9 million for a single treatment. That's obviously an enormous dollar amount, and payers generally don't like paying that kind of cost upfront, even when a one-time therapy could potentially be less expensive over the long term than years of continuous treatment.

It's also an important moment for Ultragenyx. This is their second FDA approval in the last month, and they've established 25 centers capable of delivering the gene therapy, with plans to expand that to 40.

So this isn't just about getting therapy approved. It's also about building the infrastructure to actually get these therapies to patients.

Rare Disease Impact Initiative

The FDA's Center for Devices and Radiological Health (CDHR) introduced its Rare Disease Impact Initiative.

While we tend to focus on drug therapies to manage patients with rare conditions, there are many diseases that rely on medical devices to manage and/or monitor patients. At last count, the FDA listed over 2000 devices that are being used to help people with rare conditions.

The FDA's Rare Disease Impact Initiative is designed to help medical-device developers work more directly with the FDA as they develop products for rare disease populations.

It's another part of the rare disease ecosystem that we think deserves more attention.

Looking Ahead

Several important FDA decisions are coming up.

September 26: Mirum's therapy for fibrodysplasia ossificans progressiva, or FOP.

September 27: Tlevar Therapeutics' therapy for cholangiocarcinoma and Praxis' therapy for SCN2A and SCN8A deficiencies.

September 28: Egetis Therapeutics' orphan drug to treat patients with MCT8 deficiency.

References

FDA approves new SMA drug

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-therapy-target-muscle-loss-spinal-muscular-atrophy

FDA approves gene therapy for MPS IIIA

https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapy-pediatric-patients-sanfilippo-syndrome-type

CDRH Rare Disease Impact Initiative

https://www.fda.gov/about-fda/center-devices-and-radiological-health/cdrh-rare-disease-impact-initiative

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