Nona Baker, Co-Chair of MPN Voice and patient, discusses her journey with essential thrombocythemia (ET) and polycythemia vera (PV), including diagnosis and treatment.

ET is a condition characterized by an overproduction of platelets. Abnormal blood clotting is common in these patients and may cause strokes or temporary stroke-like episodes, leg pain, swelling, pulmonary embolism, chest pain and difficulty breathing. A paradoxical problem in ET is abnormal bleeding, such as excessive nosebleeds, bleeding gums, or bleeding in the gastrointestinal tract. Other signs and symptoms include splenomegaly, weakness, headaches, or a sensation in the skin of burning, tingling, or prickling. Some people with ET have episodes of severe pain, redness, and swelling, which commonly occur in the hands and feet.

PV is a condition characterized by an increased production of red blood cells. Affected people may also have excess white blood cells and platelets. The excess cell levels lead to thicker blood and increased risk for serious thrombotic events and stroke. PV occurs more frequently in men than it does in women. The condition has been associated with genetic changes in the JAK2 and TET2 genes. Both conditions are considered myeloproliferative neoplasms (MPNs).

Ms. Baker’s symptoms first presented as painful feet/legs and extreme fatigue. After bouncing a few doctors who gave her orthopedic insoles and believed she had an alcohol problem, a retest of her bloodwork led to a hematology referral. She was finally diagnosed with essential thrombocythemia (ET) in 1991 and polycythemia vera (PV) in 2004, a time where information on these disorders was scarce. At the time, she was told she had 15 years to live. She notes that her story is similar to a lot of other patients.

After diagnosis, Ms. Baker was first treated with a chemotherapy pill and regular venesections. Now, she goes every 8-9 weeks for monitoring and receives treatment whenever her levels become unstable. However, side effects from the medications have caused skin problems, including actinic keratosis and, more recently, basal-cell carcinomas. This highlights the need for further research and treatment options for patients with ET and PV.

Ms. Baker stresses that education is key. The more people are aware of MPNs, and know what signs to look for, the faster patients can be referred to hematologists and receive an earlier diagnosis. MPN Voice works to increase education through their mission to provide clear and accurate information and emotional support to everyone who has been diagnosed with an MPN and their families/friends. The organization’s “Buddy Programme” connects newly diagnosed patients with those who have already gone through the challenges of diagnosis and beginning treatment.

To learn more about MPNs and other rare hematologic disorders, visit https://checkrare.com/diseases/hematologic-disorders/

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On September 28th, the FDA approved Emcitate, or tiratricol, from Egetis Therapeutics. It's the first-ever treatment for MCT8 deficiency, a condition also known as Allan-Herndon-Dudley syndrome. 

MCT8 deficiency is a rare genetic disorder that mostly affects boys because the gene is on the X chromosome. The gene here makes a transporter protein called MCT8, which carries thyroid hormone into cells. When that transporter doesn't work, it creates two problems. One is central, and one is peripheral. On the central side, the brain is starved of thyroid hormone, and this leads to numerous developmental concerns. On the peripheral side, excess thyroid hormone builds up in the bloodstream and can be toxic, creating chronic stress on the heart and metabolism.

Emcitate lowers excess thyroid hormone circulating in the blood, which is what this approval targets: peripheral toxicity.  The FDA based its decision on two studies that showed reductions in excess thyroid hormone levels in the blood, along with improvements in heart rate and blood pressure.

Emcitate received five major FDA designations, including orphan drug, rare pediatric disease, fast track, breakthrough therapy, and priority review. That's a pretty strong signal of how seriously the FDA viewed this condition.

On September 25th, the FDA approved Gazyva, or obinutuzumab, from Genentech to reduce the risk of relapse in patients ages 2 years and older with frequently relapsing or steroid-dependent childhood-onset idiopathic nephrotic syndrome who are in complete remission. Genentech is calling it the first FDA-approved treatment option for this condition in 70 years.  

Nephrotic syndrome happens when the kidney's filter starts leaking large amounts of protein into the urine. As protein is lost, albumin levels in the blood drop, fluid shifts into the tissues, and patients develop swelling, often first around the eyes and in the legs. They also have high cholesterol and a higher risk of infections and blood clots.  

Steroids are the first-line treatment and usually work, but more than 70% of patients relapse, and long term use of steroids has its own set of problems.

Gazyva is a monoclonal antibody that targets CD20 on B cells. In the Phase 3 INShore study, 95 percent of patients on Gazyva stayed in complete remission without relapse through week 52.

Gazyva actually started in blood cancers, where it targets B cells. Then it moved into lupus nephritis, and now it's approved for another kidney disease. So we're seeing Gazyva move from cancer into autoimmune diseases.

And Genentech isn't stopping there. It's studying Gazyva in other disorders. So once a drug proves it can target a particular mechanism, companies can look for other diseases where that same approach might work.

The Myasthenia Gravis Foundation of America held its 2026 Scientific Session on September 29th in Orlando, alongside the AANEM Annual Meeting. And industry showed up in force for myasthenia gravis: Johnson & Johnson had 26 abstracts, argenx had 18, Alexion and AstraZeneca had 15, UCB had 5, and Amgen had 2.  

Myasthenia gravis is an autoimmune disease in which a person's own antibodies attack the junction where nerves signal muscles to contract, most often by targeting the acetylcholine receptor.  

Myasthenia gravis is also a great model for studying autoimmune diseases. Researchers have a better understanding of the pathophysiology, the chain of events that creates these immune overreactions,  and how to measure outcomes reliably. 

Right now there are three main approaches for myasthenia gravis. The first is FcRn blockers. The second is complement inhibitors. The third approach goes further upstream and targets the B cells that make the antibodies.  So you have drugs that remove the antibodies, drugs that block the damage they cause, and drugs that reduce their production. 

None target the ACHR antibody exactly, but they do target the immune system that produces those autoantibodies. And that knowledge is transferable to other autoimmune conditions, ones that are not as fully understood as myasthenia gravis. 

For patients with other rare autoimmune diseases, that's encouraging. A therapy developed and validated in one disease may ultimately give researchers a faster path to treating another.

References

FDA Approves First Treatment for MCT8 Deficiency https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-mct8-deficiency 

FDA Approves Gazyva for Idiopathic Nephrotic Syndrome in Patients Aged 2 and Older https://www.gene.com/media/statements/ps_092526 

2026 MGFA Scientific Session https://myasthenia.org/events/2026-scientific-session/ 

FDA Approves Uplizna for the Treatment of Generalized Myasthenia Gravis https://checkrare.com/fda-approves-uplizna-for-the-treatment-of-generalized-myasthenia-gravis/

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On September 28th, the FDA approved Emcitate, or tiratricol, from Egetis Therapeutics. It's the first-ever treatment for MCT8 deficiency, a condition also known as Allan-Herndon-Dudley syndrome.

MCT8 deficiency is a rare genetic disorder that mostly affects boys because the gene is on the X chromosome. The gene here makes a transporter protein called MCT8, which carries thyroid hormone into cells. When that transporter doesn't work, it creates two problems. One is central, and one is peripheral. On the central side, the brain is starved of thyroid hormone, and this leads to numerous developmental concerns. On the peripheral side, excess thyroid hormone builds up in the bloodstream and can be toxic, creating chronic stress on the heart and metabolism.

Emcitate lowers excess thyroid hormone circulating in the blood, which is what this approval targets: peripheral toxicity. The FDA based its decision on two studies that showed reductions in excess thyroid hormone levels in the blood, along with improvements in heart rate and blood pressure.

Emcitate received five major FDA designations, including orphan drug, rare pediatric disease, fast track, breakthrough therapy, and priority review. That's a pretty strong signal of how seriously the FDA viewed this condition.

On September 25th, the FDA approved Gazyva, or obinutuzumab, from Genentech to reduce the risk of relapse in patients ages 2 years and older with frequently relapsing or steroid-dependent childhood-onset idiopathic nephrotic syndrome who are in complete remission. Genentech is calling it the first FDA-approved treatment option for this condition in 70 years.

Nephrotic syndrome happens when the kidney's filter starts leaking large amounts of protein into the urine. As protein is lost, albumin levels in the blood drop, fluid shifts into the tissues, and patients develop swelling, often first around the eyes and in the legs. They also have high cholesterol and a higher risk of infections and blood clots.

Steroids are the first-line treatment and usually work, but more than 70% of patients relapse, and long term use of steroids has its own set of problems.

Gazyva is a monoclonal antibody that targets CD20 on B cells. In the Phase 3 INShore study, 95 percent of patients on Gazyva stayed in complete remission without relapse through week 52.

Gazyva actually started in blood cancers, where it targets B cells. Then it moved into lupus nephritis, and now it's approved for another kidney disease. So we're seeing Gazyva move from cancer into autoimmune diseases.

And Genentech isn't stopping there. It's studying Gazyva in other disorders. So once a drug proves it can target a particular mechanism, companies can look for other diseases where that same approach might work.


The Myasthenia Gravis Foundation of America held its 2026 Scientific Session on September 29th in Orlando, alongside the AANEM Annual Meeting. And industry showed up in force for myasthenia gravis: Johnson & Johnson had 26 abstracts, argenx had 18, Alexion and AstraZeneca had 15, UCB had 5, and Amgen had 2.

Myasthenia gravis is an autoimmune disease in which a person's own antibodies attack the junction where nerves signal muscles to contract, most often by targeting the acetylcholine receptor.

Myasthenia gravis is also a great model for studying autoimmune diseases. Researchers have a better understanding of the pathophysiology, the chain of events that creates these immune overreactions, and how to measure outcomes reliably.

Right now there are three main approaches for myasthenia gravis. The first is FcRn blockers. The second is complement inhibitors. The third approach goes further upstream and targets the B cells that make the antibodies. So you have drugs that remove the antibodies, drugs that block the damage they cause, and drugs that reduce their production.

None target the ACHR antibody exactly, but they do target the immune system that produces those autoantibodies. And that knowledge is transferable to other autoimmune conditions, ones that are not as fully understood as myasthenia gravis.

For patients with other rare autoimmune diseases, that's encouraging. A therapy developed and validated in one disease may ultimately give researchers a faster path to treating another.

References
FDA Approves First Treatment for MCT8 Deficiency
https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-mct8-deficiency

FDA Approves Gazyva for Idiopathic Nephrotic Syndrome in Patients Aged 2 and Older
https://www.gene.com/media/statements/ps_092526

2026 MGFA Scientific Session
https://myasthenia.org/events/2026-scientific-session/

FDA Approves Uplizna for the Treatment of Generalized Myasthenia Gravis
https://checkrare.com/fda-approves-uplizna-for-the-treatment-of-generalized-myasthenia-gravis/

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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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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/

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Michael Benatar, MD, PhD, Department of Neurology and ALS Center, University of Miami Miller School of Medicine, discusses the use of plasma proteomics in predicting clinical manifestations of amyotrophic lateral sclerosis (ALS).

ALS is a rare motor neuron disease characterized by problems with muscle control and movement. Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or difficulty chewing or swallowing. There are various types of ALS depending on symptoms, and sometimes, genetic cause. Most people with ALS have a sporadic form of ALS. It is believed that these cases are caused by an interaction between genetic and environmental factors. Familial ALS may be caused by genetic changes in any one of several genes and the pattern of inheritance varies depending on the gene involved.

A study published in Nature Medicine looked at longitudinal plasma proteomics to predict phenoconversion to clinically manifest ALS. The study was conducted in patients with pre-symptomatic ALS to predict which unaffected carriers of ALS-associated pathogenic variants will phenoconvert to clinically manifest disease and when, with the hopes of designing more effective disease prevention trials.

A total of 516 serially collected plasma samples from 33 phenoconverters, 35 patients with ALS, 10 pre-symptomatic pathogenic variant carriers, and 59 controls were included. 92 proteins were then identified with concentrations that changed before phenoconversion and the longitudinal trajectory of these proteins was characterized. A core panel of 19 proteins was identified which, collectively, predicted phenoconversion over the 0.5-year to 5-year time horizons and resulted in estimates of time to phenoconversion with a mean absolute error of 1.6 years.

These findings were partially replicated in UK Biobank data, confirming pre-symptomatic increases in several proteins (including NEFL, EDA2R and CA3) and that a multi-protein panel outperformed NEFL alone in estimating time to phenoconversion.

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

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Lukasz Jarzyna, Vice President of Rare Disease at LEO Pharma, discusses the Priority Review for dersimelagon in the treatment of erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP).

EPP and XLP are rare congenital metabolic disorders characterized by an inborn error of porphyrin-heme biosynthesis. Signs and symptoms include painful cutaneous photosensitivity that results in tingling, burning, pain, and itching within minutes of sun/light exposure and may be accompanied by swelling and redness. Other symptoms may include erythrodontia, red discoloration of urine, hemolytic anemia, and splenomegaly.

On September 18, the US Food and Drug Administration (FDA) announced Priority Review to the New Drug Application (NDA) for dersimelagon for the treatment of EPP and XLP, with a PDUFA date of February 2027. Dersimelagon is an investigational, once-daily oral small-molecule MC1R agonist being developed for EPP and XLP. Under a Priority Review designation, the FDA aims to take action on an application within 6 months, compared to 10 months under standard review. LEO Pharma also announced an acquisition of worldwide rights to dersimelagon from Tanabe Pharma.

Earlier this year, Tanabe Pharma announced results from the global, randomized, double-blind, placebo-controlled phase 3 INSPIRE clinical trial (NCT06144840). Dersimelagon demonstrated statistically significant and clinically meaningful outcomes across primary and secondary endpoints, including a significant prolongation of average daily sunlight exposure time to first prodromal symptoms.

If approved, dersimelagon could become the first oral treatment for EPP and XLP. Dersimelagon has not yet been approved by the FDA or any other regulatory authority, and its safety and efficacy have not been established by any regulatory authority.

For more information, visit https://leo-pharma.com/media-center/news/leo-pharma-announces-fda-acceptance-of-dersimelagon-nda-with-priority-review-and-closes-acquisition-from-tanabe-pharma/

To learn more about EPP and XLP and other rare skin conditions, visit https://checkrare.com/diseases/skin-conditions/

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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 (https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/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/

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.

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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 Zanvastro (zilganersen) to treat patients with Alexander disease.

Alexander disease is a rare leukodystrophy that impairs neuronal signalling. Most cases of Alexander disease begin before age 2 and are described as the infantile form. Signs and symptoms of the infantile form typically include an enlarged brain and head size, seizures, stiffness in the arms and/or legs, intellectual disability, and developmental delay. Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers. These deposits are found in specialized cells called astroglial cells, which support and nourish other cells in the central nervous system.

Zilganersen is an antisense oligonucleotide that binds to RNA and is designed to inhibit production of excess glial fibrillary acidic protein (GFAP) that accumulates as a result of pathogenic variants in the GFAP gene. It is the first and only disease modifying therapy approved for this indication. 

The approval is based on positive results from a global, multicenter, randomized, double-blind, controlled, multiple-ascending dose (MAD) phase 1-3 study (NCT04849741 (https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fclinicaltrials.gov%2Fstudy%2FNCT04849741&esheet=54519376&newsitemid=20260421814919&lan=en-US&anchor=NCT04849741&index=3&md5=f9ebfd113b7963ede6ce50f2b736f5b6) ) that enrolled 54 participants with Alexander disease. 

The study met its primary endpoint in individuals 5 years of age and older, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT) compared to control at week 61. The treatment also demonstrated a favorable safety and tolerability profile, with most adverse events being mild or moderate in severity.

Alexander disease faces a unique challenge to getting on newborn screening panels. Although the disease does typically present in young children, GFAP accumulation may not be high enough to detect at birth. Dr. Waldman explains that research is still being done to determine when the earliest possible diagnosis can be made. However, she highlights the following red flag symptoms that may point to central nervous system involvement and may warrant genetic testing: in younger children these include gross motor and developmental delays, seizures, and in older children, these include more mild symptoms such as hypernasal speech, speech delay, vomiting, and gait imbalance.

For more information on the approval, visit https://ir.ionis.com/news-releases/news-release-details/zanvastrotm-zilganersen-approved-fda-first-and-only-disease

To learn more about Alexander disease 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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