Jane Salmon, MD, Professor of Medicine at Weill Cornell Medical College, discusses antiphospholipid syndrome (APS), its impact on pregnancy, and emerging research into Cimzia (certolizumab pegol) as a potential approach to preventing serious pregnancy complications.

View the full interview at https://checkrare.com/fda-grants-breakthrough-therapy-designation-to-cimzia-for-pregnancy-complications-in-antiphospholipid-syndrome/

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Kyle Loh, PhD, Associate Professor at Stanford Medicine, discusses research that could help scientists better understand spinal muscular atrophy (SMA) by generating new motor neurons from human hindbrain cells in the laboratory.

View the full interview at https://checkrare.com/new-stem-cell-method-could-advance-research-into-spinal-muscular-atrophy/

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Keisha L. Gibson, MD, MPH, pediatric nephrologist at the UNC School of Medicine, discusses the approval of Gazyva (obinutuzumab) for patients with childhood-onset idiopathic nephrotic syndrome (INS).

INS is a rare, autoimmune kidney disease that is often managed by corticosteroids and/or mycophenolate mofetil. The disease and treatment however, is characterized by unpredictable relapses that cause fatigue, swelling, weight gain and increased susceptibility to infections and clotting. These flare-ups or relapses also lead to anxiety, depression and reduced self-esteem, brought on by the fear of relapse and social isolation. It is usually diagnosed in early childhood and is the most common form of primary glomerular disease in children.

Obinutuzumab is a humanized type II anti-CD20 monoclonal antibody that binds to the CD20 antigen, a proven target for CD20+ B cells. It is the first treatment option for INS to be approved in 70 years. It is currently indicated to reduce the risk of relapse in adult and pediatric patients 2 years of age and older with frequently relapsing or steroid dependent childhood-onset INS who are in complete remission.

The approval is based on results from the phase 3 INShore clinical trial (NCT05627557 (https://genentech-clinicaltrials.com/en/trials/kidney-disorder/childhood-nephrotic-syndrome/a-study-to-evaluate-the-efficacy-and-safety-of-obinutuz-25529.html) ). More obinutuzumab-treated patients experienced no relapses after week 8 and were in complete remission at one year (95%) compared with mycophenolate mofetil (MMF) (73%). Analysis of key secondary endpoints showed statistically significant and clinically meaningful benefits with obinutuzumab with an increase in those with overall relapse-free survival, median time to first relapse or death, and fewer relapses from baseline to week 52, all compared with MMF. Additionally, no new safety signals were observed.

This approval is significant to patients and families living with INS because it provides an alternative treatment option to daily oral medications and the toxicities associated with chronic steroid use.

For more information on this approval, visit https://www.gene.com/media/statements/ps_092526 or https://checkrare.com/fda-approves-gazyva-obinutuzumab-for-treatment-of-childhood-onset-idiopathic-nephrotic-syndrome/

To learn more about INS and other rare kidney conditions, visit https://checkrare.com/diseases/kidney-and-urinary-diseases/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

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Kyle Loh, PhD, Associate Professor at Stanford Medicine, discusses research that could help scientists better understand spinal muscular atrophy (SMA) by generating new motor neurons from human hindbrain cells in the laboratory.    

SMA is a genetic neuromuscular disorder characterized by the loss of motor neurons, causing progressive muscle weakness and loss of movement due to atrophy. SMA mainly affects the muscles involved in walking, sitting, arm movement, and head control. Breathing and swallowing may also become difficult as the disease progresses. SMA is caused by genetic mutations in the SMN1 gene. Extra copies of the nearby related gene, SMN2, modify the severity of SMA, with type 1 being the most severe and type 4 the least severe. 

The study by Dr. Loh and his colleagues examined how different parts of the brain develop and use that knowledge to create new ways to generate new cells, including motor neurons. While the brain is often viewed as a single organ originating from one source, it is actually built from two distinct sources: one creating the forebrain/midbrain and another creating the hindbrain. As Dr. Loh explains, this distinction is critical for understanding the evolution of the brain and for developing human neurons in a laboratory setting.

Neurons in the hindbrain have received less attention than the well-studied spinal cord motor neurons. However, these hindbrain neurons are essential for life-sustaining functions, including eating, swallowing, speech, and facial movements. To study these neurons, specific genes that mark different progenitor cells were identified: OTX2 for forebrain/midbrain and GBX2 for the hindbrain. By directing stem cells toward these specific progenitor states, hindbrain motor neurons can be generated in a petri dish.

This study includes the creation of human induced pluripotent stem cell lines from patients with type 1 SMA to observe how the condition affects the growth of hindbrain motor neurons.

Dr. Loh is also interested in exploring the pathophysiology of SMA further. For example, the SMN1 gene is ubiquitously expressed in every cell in the body, its loss specifically impacts a small subset of motor neurons in patients with SMA. Further work is also needed to investigate why certain motor neurons, such as those innervating the diaphragm, appear resilient in  patients with SMA while muscles nearby are impacted. Understanding this natural resilience could offer a new approach to therapy that moves beyond simply replacing the missing gene.

For more information, visit https://www.nature.com/articles/s41593-026-02433-7

To learn more about SMA and other rare neurological conditions, visit https://checkrare.com/diseases/neurology-nervous-system-diseases/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

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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

To learn more about AML and other rare cancers, visit https://checkrare.com/diseases/cancers/

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.



Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional phys...

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Jorge Nieva, MD, Associate Professor at the Keck School of Medicine, discusses new analyses from the TRUST studies evaluating taletrectinib in patients with ROS1-positive non-small cell lung cancer (NSCLC).

ROS1-positive NSCLC is a rare molecular subtype of non-small cell lung cancer in which changes involving the ROS1 gene can drive tumor growth. Identifying ROS1-positive disease is important because these patients may benefit from targeted therapies designed to inhibit ROS1 signaling.

Taletrectinib is a next-generation ROS1 tyrosine kinase inhibitor being evaluated for the treatment of patients with advanced ROS1-positive NSCLC. At the 2026 World Conference on Lung Cancer, investigators presented new analyses from the TRUST studies examining the efficacy of taletrectinib across key patient subgroups.

The analyses demonstrated consistent efficacy across the evaluated subgroups, with responses showing durability in patients with advanced ROS1-positive NSCLC. These findings provide additional insight into the potential clinical benefit of taletrectinib across a range of patient characteristics and treatment histories.

Dr. Nieva discusses the TRUST study findings and explains the importance of evaluating both the magnitude and durability of response when considering treatment options for patients with ROS1-positive NSCLC.

The safety profile of taletrectinib was also evaluated in the TRUST studies. Dr. Nieva reviews the most commonly reported adverse events and discusses considerations for managing treatment-related toxicities in clinical practice.

As targeted therapies continue to evolve for patients with ROS1-positive NSCLC, the TRUST findings provide additional information about the efficacy and safety of taletrectinib and its potential role in the treatment of this rare form of lung cancer.

To learn more about NSCLC and other rare lung conditions, visit https://checkrare.com/diseases/lung-diseases/

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

Explore additional physician interviews, podcasts, CME activities, and rare disease resources at CheckRare.com.

Subscribe to the CheckRare Podcast Network for expert conversations, weekly news, accredited education, and the latest advances across the rare disease community.

Part of the CheckRare Podcast Network: Trusted conversations, news, education, and expert insights across the rare disease community.

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In this episode, we discuss Ultragenyx’s Priority Review Voucher that sold for $210 million, the efficacy of newborn screening on MLD, and ethical considerations needed to design and conduct clinical trials. 

This past week, Ultragenyx sold its Priority Review Voucher for $210 million.
The company received a PRV for the approval of their glycogen storage disease type Ia treatment, which was approved earlier this year.

As we have discussed on this podcast, the priority review voucher, or PRV, is an initiative the FDA introduced over a decade ago to encourage companies to develop therapies for pediatric conditions. And that program seems to be effective. 

We have followed several PRV transactions for years, and $210 million is toward the high end of the range, which has often been around $100 million to $150 million range. 

What's interesting is why these vouchers are so valuable. They allow a company to shorten the FDA review period from 10 months to 6 months. In a competitive market, getting a product approved four months sooner can be worth a tremendous amount of money.
For smaller biotech companies, selling a voucher can also provide meaningful capital to support broader development programs. So this is more than a regulatory story—it's also a story about how the economics of rare disease drug development work.

A recent publication looked at the efficacy of newborn screening to detect and treat metachromatic leukodystrophy, or MLD, in Europe. 

MLD is a rare neurodegenerative disorder. Children with the condition are born looking healthy but as toxins buildup and reach a threshold, cognitive, motor,  and behaviour abilities quickly decline. MLD does have a treatment available, but it is only indicated for patients who are diagnosed before that decline occurs. Which creates a bit of a catch-22; the baby looks healthy, so there is no reason to test them for this very rare condition. And once symptoms appear, it is too late to start treatment. Hence the need for newborn screening.

The study from Europe, shows that newborn screening dramatically changes the outcomes in these children. They found 7 babies with early onset MLD. All seven were treated and so far, their neurological functions are normal. That only happens if they get treated before symptoms appear. The treatment, developed by Orchard Therapeutics is an ex vivo gene therapy. And Orchard Therapeutics is working, along with several advocacy groups, to get MLD on NBS panels.

Identify patients that can benefit from treatment is a major challenge in rare disease. 
That's especially true for conditions like MLD, where treatment may be most effective before symptoms appear and irreversible neurological damage occurs.

Newborn screening can help close that gap by identifying affected babies before they become visibly ill. But getting a disease added to screening programs requires evidence, coordination, and time. The bigger lesson is that developing a treatment is only one part of the equation. We also need systems that identify patients early enough for that treatment to make a difference.

Another publication by the International Society of CNS Clinical Trials and Methodology (ISCTM) Orphan Diseases Working Group looked at ethical considerations needed to design and conduct clinical trials. 

This working group has its work cut out for it, but it's necessary. There are many ethical dilemmas for rare neurological diseases, especially those involving children.  

For example, we all want these trials to be placebo-controlled studies, but that can be difficult, or perceived to be unethical, if there is no standard treatment to act as the control group.  Other considerations, such as age and cognitive abilities, can also create ethical concerns that need to be addressed. 

Developing a therapy for an ultra-rare disease is already difficult because patient populations are small, recruitment is challenging, and the evidence base may be limited.

Companies also need a clear understanding of what constitutes an acceptable and scientifically meaningful clinical trial. Without that guidance, they face greater uncertainty about whether a study will generate evidence regulators can use to evaluate a treatment.

The goal isn't to lower the standards for evidence. It's to develop approaches that are both ethically sound and practical for these very small patient populations. That can help researchers generate meaningful results and give companies greater confidence to invest in diseases that might otherwise be overlooked.

References
Ultragenyx sells PRV for $210M
https://www.globenewswire.com/news-release/2026/10/07/3376457/20739/en/ultragenyx-enters-into-agreement-to-sell-rare-pediatric-disease-priority-review-voucher-for-210-million.html  

CheckRare’s Priority Review Voucher 
https://checkrare.com/priority-review-voucher/

Metachromatic leukodystrophy and newborn screening
https://link.springer.com/article/10.1186/s13023-026-04620-y 

Ethical considerat...

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In this episode, we discuss Ultragenyx’s Priority Review Voucher that sold for $210 million, the efficacy of newborn screening on MLD, and ethical considerations needed to design and conduct clinical trials.

This past week, Ultragenyx sold its PRV for $210 million.

The company received a PRV for the approval of their glycogen storage disease type Ia treatment, which was approved earlier this year.

As we have discussed on this podcast, the priority review voucher, or PRV, is an initiative the FDA introduced over a decade ago to encourage companies to develop therapies for pediatric conditions. And that program seems to be effective.

We have followed several PRV transactions for years, and $210 million is toward the high end of the range, which has often been around $100 million to $150 million range.

What's interesting is why these vouchers are so valuable. They allow a company to shorten the FDA review period from 10 months to 6 months. In a competitive market, getting a product approved four months sooner can be worth a tremendous amount of money.

For smaller biotech companies, selling a voucher can also provide meaningful capital to support broader development programs. So this is more than a regulatory story—it's also a story about how the economics of rare disease drug development work.

A recent publication looked at the efficacy of newborn screening to detect and treat metachromatic leukodystrophy, or MLD, in Europe.

MLD is a rare neurodegenerative disorder. Children with the condition are born looking healthy but as toxins buildup and reach a threshold, cognitive, motor, and behaviour abilities quickly decline. MLD does have a treatment available, but it is only indicated for patients who are diagnosed before that decline occurs. Which creates a bit of a catch-22; the baby looks healthy, so there is no reason to test them for this very rare condition. And once symptoms appear, it is too late to start treatment. Hence the need for newborn screening.

The study from Europe, shows that newborn screening dramatically changes the outcomes in these children. They found 7 babies with early onset MLD. All seven were treated and so far, their neurological functions are normal. That only happens if they get treated before symptoms appear. The treatment, developed by Orchard Therapeutics is an ex vivo gene therapy. And Orchard Therapeutics is working, along with several advocacy groups, to get MLD on NBS panels.

Identify patients that can benefit from treatment is a major challenge in rare disease.

That's especially true for conditions like MLD, where treatment may be most effective before symptoms appear and irreversible neurological damage occurs.

Newborn screening can help close that gap by identifying affected babies before they become visibly ill. But getting a disease added to screening programs requires evidence, coordination, and time. The bigger lesson is that developing a treatment is only one part of the equation. We also need systems that identify patients early enough for that treatment to make a difference.

Another publication by the International Society of CNS Clinical Trials and Methodology (ISCTM) Orphan Diseases Working Group looked at ethical considerations needed to design and conduct clinical trials.

This working group has its work cut out for it, but it's necessary. There are many ethical dilemmas for rare neurological diseases, especially those involving children.

For example, we all want these trials to be placebo-controlled studies, but that can be difficult, or perceived to be unethical, if there is no standard treatment to act as the control group. Other considerations, such as age and cognitive abilities, can also create ethical concerns that need to be addressed.

Developing a therapy for an ultra-rare disease is already difficult because patient populations are small, recruitment is challenging, and the evidence base may be limited.

Companies also need a clear understanding of what constitutes an acceptable and scientifically meaningful clinical trial. Without that guidance, they face greater uncertainty about whether a study will generate evidence regulators can use to evaluate a treatment.

The goal isn't to lower the standards for evidence. It's to develop approaches that are both ethically sound and practical for these very small patient populations. That can help researchers generate meaningful results and give companies greater confidence to invest in diseases that might otherwise be overlooked.

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Andrew Dauber, MD, MMsc, Chief of Endocrinology at Children’s National, discusses the efficacy of vosoritide to treat persons with hypochondroplasia.

Hypochondroplasia is a rare skeletal disease characterized by very short stature, similar to achondroplasia, but with milder features. People with hypochondroplasia usually have very short stature, large head, accentuated lordosis, short arms and legs, and broad, short hands and feet. Other features include a limited range of motion in the elbows, lordosis, and bowed legs. Uncommon symptoms may include learning difficulties and convulsions. Hypochondroplasia is often caused by genetic changes in the FGFR3 gene.

Vosoritide is a C-type natriuretic peptide analogue being investigated for the treatment of hypochondroplasia. It is currently approved for the treatment of achondroplasia.

In the phase 3, multicenter CANOPY-HCH-3 (NCT06455059) clinical trial, children with hypochondroplasia who were 3 to less than 18 years of age were randomly assigned to receive once-daily subcutaneous injections of vosoritide or placebo for 52 weeks per weight-band dosing regimen.

A total of 81 participants were randomly assigned to receive vosoritide or placebo. At week 52, the least squares mean (LSM) change from baseline in annualized growth velocity was 1.95 cm/year with vosoritide versus −0.39 cm/year with placebo. Dr. Dauber also explains that patients in the vosoritide group also showed an increase in arm span of more than a centimeter compared to the placebo group.

87.8% of participants in the vosoritide group and 72.5% of the placebo group experienced at least one adverse event. There were no reports of grade 3 or higher adverse events, adverse events leading to treatment discontinuation, or deaths.

For more information, visit The New England Journal of Medicine Evidence.

To learn more about hypochondroplasia and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-diseases/

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