In this episode, endocrinologist Margarita Ochoa-Maya, MD, speaks with endocrinologist Katherine Arakay, MD, of the University of California, Los Angeles (UCLA), about clinical trials for rare endocrine disorders. The conversation examines clinical trials from three perspectives: patients, clinical researchers, and sponsors.

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Naji Gehchan, MD, MBA, Chief Medical and Development Officer at Kyverna Therapeutics, discusses one-year data showing sustained benefits of KYV-101 (mivocabtagene autoleucel ; Miv-cel) in stiff person syndrome (SPS), along with longer-term follow-up data in generalized myasthenia gravis (gMG).

SPS and gMG are rare neurological and neuromuscular disorders:

SPS: SPS is a rare, progressive neurological autoimmune disease that causes muscle stiffness and painful spasms that can affect walking and mobility. Up to 80% of patients lose their mobility over time, and there are currently no FDA-approved treatments. 

gMG: gMG is a rare autoimmune neuromuscular disease characterized by muscle weakness and fatigue. As the disease progresses, it can interfere with daily activities, such as speaking, chewing, swallowing, and breathing. 

Positive one-year topline data from the KYSA-8 clinical trial (NCT06588491) were announced on September 24, 2026. KYSA-8 was a registrational, phase two, open-label, single-arm, multicenter study of miv-cel.

Miv-cel is a fully human, autologous, CD19-targeting CAR T-cell therapy with CD28 co-stimulation. It’s designed to achieve deep B-cell depletion, reset the immune system, and deliver durable drug-free, disease-free remission in autoimmune diseases with a single dose. 

A total of 26 adult patients who had an inadequate response to at least one immunotherapy treatment participated in the study. Each participant received a single dose of miv-cel. Among patients who achieved a clinically meaningful improvement in the timed 25-foot walk at primary analysis, 95% maintained that benefit at 12 months. Of the 12 patients who needed a walking aid before treatment, 67% still did not require assistance at the 12-month follow-up. Furthermore, 92% of patients remained off chronic immunotherapies for SPS. 

Also announced were longer-term follow-up data for its KYSA-6 trial (NCT06193889). KYSA-6 is a phase 2/3 trial evaluating miv-cel, administered as a single dose, in patients with gMG.  

A total of seven adult patients participated in the study. Follow-up now extends to one year and beyond (up to 1.5 years) in five patients, with one patient at 9 months and another at 6 months. All seven participants achieved clinically meaningful improvements in both the Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores at 24 weeks, while all five participants with at least one year of follow-up maintained clinically meaningful improvements. Additionally, six of the seven patients remained off immunosuppressant therapies at their latest follow-up.   

Miv-cel continued to be well-tolerated in both studies. In the KYSA-8 trial, no high-grade cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) and no cases of immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS) were reported through the 12-month follow-up.

In the KYSA-6  trial, no high-grade CRS, no ICANS, and no cases of IEC-HS were reported during the available follow-up.

For more information, visit: https://ir.kyvernatx.com/news-releases/news-release-details/kyverna-therapeutics-reports-positive-one-year-data

To learn more about stiff person syndrome, myasthenia gravis, and other rare neurological and neuromuscular disorders, visit: https://checkrare.com/diseases/neurology-nervous-system-diseases/

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View the full interview at https://checkrare.com/z-basivarsen-shows-functional-improvements-in-one-year-data-for-myotonic-dystrophy-type-1/

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Laurie Gutmann, MD, professor of neurology at Indiana University, discusses data showing functional improvements with zeleciment basivarsen (z-basivarsen; DYNE-101) in patients with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1), also known as Steinert disease, is a rare, inherited type of muscular dystrophy. Its estimated worldwide prevalence is approximately 1 in 20,000 people (https://www.ncbi.nlm.nih.gov/books/NBK1165/) . DM1 impacts the muscles and other body systems, including the heart, eyes, endocrine system, and central nervous system. 

There are three forms of the disease: mild form, classic form, and congenital form (present at birth). The mild form typically causes the least severe symptoms, and patients generally have a normal lifespan. The classic form causes muscle weakness and wasting, myotonia, cataracts, and, in many cases, abnormal heart function. Adults with the classic form may become physically disabled and have a shortened lifespan. The congenital form is characterized by severe generalized weakness at birth, often accompanied by breathing complications that can be life-threatening.

DM1 is caused by an abnormal expansion of repeated DNA sequences in the DMPK gene.

Zeleciment basivarsen is an investigational therapy consisting of an antisense oligonucleotide (ASO) conjugated to an antigen-binding fragment (Fab) that binds to the transferrin receptor 1 (TfR1) to enable delivery to muscle and the central nervous system. It’s designed to improve function in individuals living with DM1 by reducing toxic DMPK RNA, releasing splicing proteins, and allowing normal mRNA processing.

Z-basivarsen has been granted Breakthrough Therapy, Orphan Drug, and Fast Track designations by the U.S. Food and Drug Administration (FDA)

Additional one-year efficacy data from the multiple ascending dose (MAD) portion of the phase 1/2 ACHIEVE trial (NCT05481879 (https://clinicaltrials.gov/study/NCT05481879) ) were announced on September 29, 2026 (https://www.globenewswire.com/news-release/2026/09/29/3371326/0/en/dyne-therapeutics-announces-additional-one-year-clinical-data-from-phase-1-2-achieve-trial-of-z-basivarsen-dyne-101-for-myotonic-dystrophy-type-1-dm1.html) , and presented at the 2026 World Muscle Society Congress and the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting. ACHIEVE is a randomized, placebo-controlled, double-blind, phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of z-basivarsen in patients with DM1.

The pooled analysis included 25 to 26 participants from three dose groups: 3.4 mg/kg every four weeks, 5.4 mg/kg every eight weeks, and 6.8 mg/kg every eight weeks. Some participants initially received a placebo before switching to active treatment. Only 8 of the 26 participants received the selected 6.8/kg dose for the full 12 months.

The pooled data showed improvements in several areas, including:

Hand myotonia: At six months, video hand opening time improved by 3.2 seconds from baseline in the pooled treatment group, compared with a 0.4-second increase in the placebo group.

Physical function: At 12 months, participants improved their five-times sit-to-stand test by 1.2 seconds and their 10-meter walk/run test by 0.3 seconds relative to baseline.

Muscle strength: Quantitative muscle testing showed improvements in both the total score and hand grip, with each increasing by 4.8% relative to baseline.

Patient-reported outcomes: The Myotonic Dystrophy Health Index total score improved by 25.2% relative to baseline.No treatment-related serious adverse events were identified.

The ACHIEVE trial's registrational expansion cohort is fully enrolled, with topline results expected in the first quarter of 2027. The study's primary endpoint is the change in video hand opening time after six months of treatment.

Dyne Therapeutics plans to use these results to support a potential U.S. accelerated approval submission in the third quarter of 2027.Dyne Therapeutics is also conducting the phase 3 HARMONIA trial to further evaluate z-basivarsen. The HARMONIA trial is intended to confirm the treatment's benefits and support a potential application for traditional FDA approval.

For more information, visit: https://www.globenewswire.com/news-release/2026/09/29/3371326/0/en/dyne-therapeutics-announces-additional-one-year-clinical-data-from-phase-1-2-achieve-trial-of-z-basivarsen-dyne-101-for-myotonic-dystrophy-type-1-dm1.html

To learn more about myotonic dystrophy type 1 and other rare neurological and neuromuscular disorders, 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 exper...

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Laurie Gutmann, MD, professor of neurology at Indiana University, discusses data showing functional improvements with zeleciment basivarsen (z-basivarsen; DYNE-101) in patients with myotonic dystrophy type 1. 

Myotonic dystrophy type 1 (DM1), also known as Steinert disease, is a rare, inherited type of muscular dystrophy. Its estimated worldwide prevalence is approximately 1 in 20,000 people. DM1 impacts the muscles and other body systems, including the heart, eyes, endocrine system, and central nervous system. 

There are three forms of the disease: mild form, classic form, and congenital form (present at birth). The mild form typically causes the least severe symptoms, and patients generally have a normal lifespan. The classic form causes muscle weakness and wasting, myotonia, cataracts, and, in many cases, abnormal heart function. Adults with the classic form may become physically disabled and have a shortened lifespan. The congenital form is characterized by severe generalized weakness at birth, often accompanied by breathing complications that can be life-threatening.

DM1 is caused by an abnormal expansion of repeated DNA sequences in the DMPK gene.

Zeleciment basivarsen is an investigational therapy consisting of an antisense oligonucleotide (ASO) conjugated to an antigen-binding fragment (Fab) that binds to the transferrin receptor 1 (TfR1) to enable delivery to muscle and the central nervous system. It’s designed to improve function in individuals living with DM1 by reducing toxic DMPK RNA, releasing splicing proteins, and allowing normal mRNA processing. 

Z-basivarsen has been granted Breakthrough Therapy, Orphan Drug, and Fast Track designations by the U.S. Food and Drug Administration (FDA).

Additional one-year efficacy data from the multiple ascending dose (MAD) portion of the phase 1/2 ACHIEVE trial (NCT05481879) were announced on September 29, 2026, and presented at the 2026 World Muscle Society Congress and the American Association of Neuromuscular & Electrodiagnostic Medicine annual meeting. ACHIEVE is a randomized, placebo-controlled, double-blind, phase 1/2 clinical trial evaluating the safety, tolerability, and efficacy of z-basivarsen in patients with DM1.

The pooled analysis included 25 to 26 participants from three dose groups: 3.4 mg/kg every four weeks, 5.4 mg/kg every eight weeks, and 6.8 mg/kg every eight weeks. Some participants initially received a placebo before switching to active treatment. Only 8 of the 26 participants received the selected 6.8/kg dose for the full 12 months.

The pooled data showed improvements in several areas, including:

Hand myotonia: At six months, video hand opening time improved by 3.2 seconds from baseline in the pooled treatment group, compared with a 0.4-second increase in the placebo group.

Physical function: At 12 months, participants improved their five-times sit-to-stand test by 1.2 seconds and their 10-meter walk/run test by 0.3 seconds relative to baseline.

Muscle strength: Quantitative muscle testing showed improvements in both the total score and hand grip, with each increasing by 4.8% relative to baseline.

Patient-reported outcomes: The Myotonic Dystrophy Health Index total score improved by 25.2% relative to baseline.

No treatment-related serious adverse events were identified.

The ACHIEVE trial's registrational expansion cohort is fully enrolled, with topline results expected in the first quarter of 2027. The study's primary endpoint is the change in video hand opening time after six months of treatment. Dyne Therapeutics plans to use these results to support a potential U.S. accelerated approval submission in the third quarter of 2027.

Dyne Therapeutics is also conducting the phase 3 HARMONIA trial to further evaluate z-basivarsen. The HARMONIA trial is intended to confirm the treatment's benefits and support a potential application for traditional FDA approval.

For more information, visit: https://www.globenewswire.com/news-release/2026/09/29/3371326/0/en/dyne-therapeutics-announces-additional-one-year-clinical-data-from-phase-1-2-achieve-trial-of-z-basivarsen-dyne-101-for-myotonic-dystrophy-type-1-dm1.html

To learn more about myotonic dystrophy type 1 and other rare neurological and neuromuscular disorders, visit: https://checkrare.com/diseases/neurology-nervous-system-diseases/

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Andrea Callaway, president and founder of The Nephrotic Syndrome Foundation, discusses the FDA approval of Gazyva (obinutuzumab) for idiopathic nephrotic syndrome (INS) and what the approval means for affected families. 

INS is a rare autoimmune kidney disease that’s commonly diagnosed in early childhood. It causes the kidneys to leak large amounts of protein into the urine, which can result in weight gain, swelling, and fatigue. Patients may also experience an increased risk of complications, such as infections and blood clots. 

Steroids have traditionally been used to treat patients with INS, but between 60% and 90% (https://www.ovid.com/jnls/jasn/fulltext/10.1681/asn.20213210s1609b~rates-of-idiopathic-childhood-nephrotic-syndrome-relapse) of patients experience relapse. Furthermore, steroid-related side effects can make long-term treatment challenging.

On September 25, 2026 (https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-treat-idiopathic-nephrotic-syndrome-patients-2-years-and-older) , obinutuzumab received FDA approval to reduce the risk of relapse in adults and children ages two years and older with frequently relapsing or steroid-dependent childhood-onset INS who are in complete remission. It’s the first treatment approved for INS in more than 70 years.

Obinutuzumab is a monoclonal antibody that targets B cells involved in immune activity. It’s designed to help INS patients maintain remission and lower the risk of relapses. 

Results from the INShore clinical trial (NCT05627557 (https://clinicaltrials.gov/study/NCT05627557?viewType=Card&term=NCT05627557&rank=1) ) were announced by Roche on October 28, 2025 (https://www.roche.com/media/releases/med-cor-2025-10-28) . The INShore study was a phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of obinutuzumab compared to mycophenolate mofetil (MMF) in patients with childhood-onset INS.

The study found that 95% of participants receiving  obinutuzumab experienced no relapses after week 8 and were in complete remission by week 52, compared with 73% of participants receiving MMF. 
Secondary endpoints included statistically significant and clinically meaningful benefits in overall relapse-free survival, median time to first relapse or death, and the number of relapses through week 52, all compared with MMF. 

No new safety signals were observed with obinutuzumab.

For more information, visit: https://www.gene.com/media/statements/ps_092526

To learn more about idiopathic nephrotic syndrome and other rare kidney and urinary diseases, 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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Andrea Callaway, president and founder of The Nephrotic Syndrome Foundation, discusses the FDA approval of Gazyva (obinutuzumab) for idiopathic nephrotic syndrome (INS) and what the approval means for affected families.

INS is a rare autoimmune kidney disease that’s commonly diagnosed in early childhood. It causes the kidneys to leak large amounts of protein into the urine, which can result in weight gain, swelling, and fatigue. Patients may also experience an increased risk of complications, such as infections and blood clots.

Steroids have traditionally been used to treat patients with INS, but between 60% and 90% of patients experience relapse. Furthermore, steroid-related side effects can make long-term treatment challenging.

On September 25, 2026, obinutuzumab received FDA approval to reduce the risk of relapse in adults and children ages two years and older with frequently relapsing or steroid-dependent childhood-onset INS who are in complete remission. It’s the first treatment approved for INS in more than 70 years.

Obinutuzumab is a monoclonal antibody that targets B cells involved in immune activity. It’s designed to help INS patients maintain remission and lower the risk of relapses.

Results from the INShore clinical trial (NCT05627557) were announced by Roche on October 28, 2025. The INShore study was a phase 3, open-label, randomized clinical trial evaluating the efficacy and safety of obinutuzumab compared to mycophenolate mofetil (MMF) in patients with childhood-onset INS.

The study found that 95% of participants receiving obinutuzumab experienced no relapses after week 8 and were in complete remission by week 52, compared with 73% of participants receiving MMF.

Secondary endpoints included statistically significant and clinically meaningful benefits in overall relapse-free survival, median time to first relapse or death, and the number of relapses through week 52, all compared with MMF.

No new safety signals were observed with obinutuzumab.

For more information, visit: https://www.gene.com/media/statements/ps_092526

To learn more about idiopathic nephrotic syndrome and other rare kidney and urinary diseases, visit:
https://checkrare.com/diseases/kidney-and-urinary-diseases/

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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 (https://clinicaltrials.gov/ct2/show/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 (https://evidence.nejm.org/doi/full/10.1056/EVIDoa2600257) .

To learn more about hypochondroplasia and other rare musculoskeletal conditions, visit https://checkrare.com/diseases/musculoskeletal-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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Researchers at Vanderbilt and the Undiagnosed Diseases Network have published a study in Nature Digital Medicine on an AI tool called RARE-PHENIX.

It focuses on diagnosing patients faster. Diagnosing a rare disease can take a long time. The authors of the paper note that the average delay is four to eight years. , and those delays are filled with misdiagnoses, inappropriate treatments, and unnecessary tests.

RARE PHENIX is focused on organizing the symptoms that physicians write down when examining a patient. Those symptoms may include symptoms that may or may not be part of rare condition. Patients, even if they have a rare condition, can have other symptoms due to comorbidities, aging, etc. Looking for patterns in the plethora of symptoms can be difficult. RARE-PHENIX organizes that chaos. It first uses a large language model to convert those listed symptoms into standardized terms. And then it ranks them as to whether they are likely due to a rare condition or not.

Testing showed the model was twice as good as ChatGPT.

An interesting aspect of this model is that it mirrors how clinicians approach a diagnosis. That produced substantially better results than a single-prompt ChatGPT approach.

Just as importantly, the tool doesn't make the diagnosis. It helps organize and prioritize the clinical clues for a physician to review. That’s a promising role for AI: helping clinicians see patterns they might otherwise miss while keeping clinical judgment a human process.

View the full podcast at

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