Margarita Ochoa-Maya, MD, and James Radke, PhD, discuss why diagnostic delays occur and what can be done to help patients reach the right diagnosis sooner.

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Marina Kremyanskaya, MD, PhD, Associate Professor at Icahn School of Medicine at Mount Sinai, discusses the phase 2 topline findings from the SANRECO clinical trial and the evolving polycythemia vera (PV) treatment landscape.

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.

The SANRECO clinical trial is a phase 2, 36-week, randomized, double-blind, placebo-controlled trial evaluating divesiran (6 mg/kg) administered subcutaneously every six weeks (Q6W) or every twelve weeks (Q12W) in 48 phlebotomy-dependent patients with PV.

Divesiran is a first-in-class siRNA designed to silence the TMPRSS6 gene, thereby increasing hepcidin production and its release by liver hepatocytes, leading to the restriction of iron to the bone marrow and, thus, reducing the excessive production of red blood cells.

The study met its primary endpoint, with 88% of patients achieving a response among divesiran-treated patients with PV, compared to 19% of those who received placebo. The primary endpoint was the proportion of patients achieving a response, defined as the absence of phlebotomy and maintenance of hematocrit below 45% during weeks 18-36. Both 6 and 8 week dosing schedules showed substantial primary endpoint efficacy with response rates of 93.8% and 81.3% for Q6W and Q12W, respectively.

The key secondary endpoint of phlebotomy rate during weeks 0-36 was also met with the mean number of phlebotomies per patient in the divesiran groups significantly reduced at 0.2, compared to placebo at 2.1. Divesiran groups also showed improvements in hematocrit control, iron markers including ferritin, and patient reported outcomes using the MPN-SAF Total Symptom Score.

Divesiran was well tolerated and safety was in line with previous trials. No new safety findings were observed in the trial. Injection site reactions were infrequent and self-limiting. There were two investigator reported grade 1 anemia adverse event cases.

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

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Carol Roberts, President of The PBCers Organization, discusses results from the Voice of PBC patient survey.

PBC is a chronic, progressive autoimmune liver disease in which the bile ducts become inflamed and damaged. This leads to the buildup of bile and causes scarring, cirrhosis, and eventual liver failure. Many people do not have symptoms when they are first diagnosed. Early symptoms may include fatigue, pruritus, and abdominal pain. As the disease progresses, people with PBC may develop weakness, nausea, diarrhea, edema, bone and joint pain, jaundice, dark urine, and xanthomas. It is thought to be caused by a combination of genetic susceptibility and environmental triggers.

In recognition of PBC Awareness Month, The PBCers Organization released results of its national Voice of PBC survey. The survey captured the lived experience of 210 patients living with PBC, revealing a heavy and often invisible burden.

In terms of the physical impact of disease, 75% of respondents received a diagnosis after an abnormal routine blood test, with no prior warning symptoms. Among patients who did notice symptoms prior to diagnosis, the most commonly reported were fatigue, itching, dry eyes and mouth, and brain fog. 57% reported severe or some impact on their physical well-being, 87% had at least one additional autoimmune or related condition alongside PBC, and 45% saw improvement in their symptoms since starting current treatment.

This survey also revealed the impact of PBC on patients’ emotional wellbeing, with 53% indicating that fear of the future and uncertainty about their long-term health is their defining emotional response. 49% felt misunderstood, 44% reported increased anxiety, and 33% reported having depression or low mood. Additionally, 51% responded that this emotional impact was severe.

Finally, the social impact of the disease highlights the stigma surrounding PBC. 60% of patients reported being told that they did not look sick and 53% had dismissively told their condition is caused by alcohol or drugs. This fear of being misjudged has led to only 30% feeling very comfortable disclosing their diagnosis to coworkers, compared to 67% with immediate family. Additionally, 48% reported severe or some impact on their social interactions and 58% reported experiencing financial strain related to their PBC.

These findings showcase the daily reality faced by patients with PBC and highlight the need to listen to patient voices and change the conversation around liver disease.

To learn more about PBC and other rare autoimmune conditions, visit https://checkrare.com/diseases/autoimmune-and-auto-inflammatory-disorders/

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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).

wAIHA is a rare hematologic autoimmune condition characterized by antibodies that attack red blood cells and lead to hemolytic anemia. Symptoms may include unusual weakness and fatigue that make daily life difficult, tachycardia, breathing difficulties, jaundice, dark urine and/or splenomegaly. The cause of wAIHA is unknown.

The US Food and Drug Administration (FDA) recently approved nipocalimab for the treatment of wAIHA in patients 12 years of age and older currently or previously treated with corticosteroids. Dr. Jones describes the approval as a major milestone that provides patients with treatment options and hope for the future of wAIHA.

Nipocalimab is an immunoselective neonatal fragment crystallizable receptor (FcRn) blocker designed to target and reduce pathogenic immunoglobulin G (IgG)  autoantibodies while preserving B-cell function. It  is the first  FDA approved treatment for wAIHA.

The approval was based on the pivotal phase 2/3 ENERGY study (NCT04119050), where patients treated with nipocalimab  demonstrated durable hemoglobin response. A mean increase in hemoglobin of 1 g/DL at week 1 and improvement in FACIT-Fatigue score at week 24 were also observed. Nipocalimab’s safety profile cwas onsistent with the established safety profile in generalized myasthenia gravis (gMG). The most common adverse reactions in patients with wAIHA treated with nipocalimab were peripheral edema, diarrhea, and fever.

Dr. Jones hopes that this treatment approval will lead to greater recognition and understanding of wAIHA, especially among physicians. This in turn can help patients get earlier referrals to hematologists and diagnoses. Additionally, Dr. Jones and patients remain hopeful for further research and a greater awareness of symptom burden.

For more information on the approval of nipocalimab, visit https://www.jnj.com/media-center/press-releases/fda-approves-imaavy-nipocalimab-aahu-as-first-ever-treatment-for-warm-autoimmune-hemolytic-anemia-waiha-representing-a-landmark-advancement-for-patients

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

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This week, three developments highlight the rapidly changing rare disease treatment landscape: a Phase 3 setback in Angelman syndrome, continued competition in hereditary angioedema, and an FDA decision expanding access to a targeted lung cancer therapy.

Angelman Syndrome: Phase 3 Trial Misses Its Marks
Ultragenyx announced results from its Phase 3 Aspire study of apazunersen in Angelman syndrome. The trial did not meet its primary or key secondary endpoints.

Angelman syndrome is a rare neurodevelopmental disorder caused by the loss of a working copy of the UBE3A gene. Patients generally have a normal lifespan but can experience significant cognitive and motor impairments requiring extensive lifelong care.

Apazunersen is designed to activate the healthy paternal copy of UBE3A, providing neurons with another potential source of the missing protein. The approach is based on a promising biological strategy that has been explored successfully in other genetic diseases, such as spinal muscular atrophy.

However, the ASPIRE trial results did not demonstrate a statistically significant change in either the primary or secondary outcomes. Ultragenyx said it was disappointed, particularly given encouraging earlier-stage results. The company will now evaluate the data and determine whether there is a path forward for the program.

The results underscore one of the challenges of rare disease drug development: promising early-stage findings do not always translate into success in larger, controlled Phase 3 trials.

HAE: Treatment Options Continue to Expand
The treatment landscape for hereditary angioedema (HAE) continues to grow.
HAE is a rare genetic disorder that causes recurrent attacks of swelling, which can affect the skin, gastrointestinal tract, or airway. Treatment includes on-demand therapies for acute attacks and prophylactic therapies designed to prevent them.

There are currently 11 approved HAE treatments, with additional therapies in development. Those in development include Pharvaris’ deucrictibant, which is an oral therapy under FDA review for acute HAE attacks, with a PDUFA date expected in April 2027. The company is also developing a longer-acting formulation of the drug for prophylaxis and has reported positive Phase 3 results.
The growing competition reflects how the HAE market has evolved. Companies are now competing not only on efficacy, but also on convenience, dosing frequency, mechanism of action, and route of administration.

It also illustrates a broader rare disease trend: once the underlying biology of a disease is understood and a therapeutic target is validated, additional treatments can follow—creating more options for patients.

Targeted Lung Cancer Therapy Moves to First-Line Treatment
The FDA has expanded the indications of sevabertinib (Hyrnuo) to include first-line treatment for advanced or metastatic non-small cell lung cancer with specific HER2 mutations.

While lung cancer is common, these molecularly defined patient populations can be relatively rare. HER2-mutated tumors account for a small percentage of NSCLC cases and occur more frequently in people who have never smoked.

Hyrnuo was initially approved in November 2025 as a second-line treatment. The new approval allows eligible patients to receive it earlier in their treatment.

The decision also uses the FDA's accelerated approval pathway, which can allow therapies to reach patients based on earlier measures of potential benefit while confirmatory studies are underway.
Bayer is conducting a Phase 3 trial, SOHO-02, comparing sevabertinib with standard therapy in the first-line setting. Those results will help determine whether the drug ultimately becomes a standard treatment for this patient population.

Looking Ahead
Two additional FDA decisions are expected September 19.
Ultragenyx's UX111 for MPS IIIA, or Sanfilippo syndrome type A, and IntraBio's Aqneursa for ataxia-telangiectasia both have PDUFA dates that day.
The decisions will be closely watched by patients, families, physicians, and the broader rare disease community.

References
Ultragenyx Announces Phase 3 Aspire Results in Angelman Syndrome
https://www.globenewswire.com/news-release/2026/09/02/3355481/20739/en/ultragenyx-announces-phase-3-aspire-results-in-angelman-syndrome.html

New HAE Drugs for Acute and Prophylactic Therapies
https://firstwordpharma.com/story/7961829 (https://firstwordpharma.com/story/7961829%20FDA%20Grants%20Accelerated%20Approval%20to%20Sevabertinib%20for%20Locally%20Advanced%20or%20Metastatic%20Non-Squamous)

FDA Grants Accelerated Approval to Sevabertinib for Locally Advanced or Metastatic Non-Squamous  Non-Small Cell Lung Cancer
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-locally-advanced-or-metastatic-non-squamous-non-small


Produced by CheckRare.

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

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This week, three developments highlight the rapidly changing rare disease treatment landscape: a Phase 3 setback in Angelman syndrome, continued competition in hereditary angioedema, and an FDA decision expanding access to a targeted lung cancer therapy.

Angelman Syndrome: Phase 3 Trial Misses Its Marks

Ultragenyx announced results from its Phase 3 Aspire study of apazunersen in Angelman syndrome. The trial did not meet its primary or key secondary endpoints.

Angelman syndrome is a rare neurodevelopmental disorder caused by the loss of a working copy of the UBE3A gene. Patients generally have a normal lifespan but can experience significant cognitive and motor impairments requiring extensive lifelong care.

Apazunersen is designed to activate the healthy paternal copy of UBE3A, providing neurons with another potential source of the missing protein. The approach is based on a promising biological strategy that has been explored successfully in other genetic diseases, such as spinal muscular atrophy.

However, the ASPIRE trial results did not demonstrate a statistically significant change in either the primary or secondary outcomes. Ultragenyx said it was disappointed, particularly given encouraging earlier-stage results. The company will now evaluate the data and determine whether there is a path forward for the program.

The results underscore one of the challenges of rare disease drug development: promising early-stage findings do not always translate into success in larger, controlled Phase 3 trials.

HAE: Treatment Options Continue to Expand

The treatment landscape for hereditary angioedema (HAE) continues to grow.

HAE is a rare genetic disorder that causes recurrent attacks of swelling, which can affect the skin, gastrointestinal tract, or airway. Treatment includes on-demand therapies for acute attacks and prophylactic therapies designed to prevent them.

There are currently 11 approved HAE treatments, with additional therapies in development. Those in development include Pharvaris’ deucrictibant, which is an oral therapy under FDA review for acute HAE attacks, with a PDUFA date expected in April 2027. The company is also developing a longer-acting formulation of the drug for prophylaxis and has reported positive Phase 3 results.

The growing competition reflects how the HAE market has evolved. Companies are now competing not only on efficacy, but also on convenience, dosing frequency, mechanism of action, and route of administration.

It also illustrates a broader rare disease trend: once the underlying biology of a disease is understood and a therapeutic target is validated, additional treatments can follow—creating more options for patients.

Targeted Lung Cancer Therapy Moves to First-Line Treatment

The FDA has expanded the indications of sevabertinib (Hyrnuo) to include first-line treatment for advanced or metastatic non-small cell lung cancer with specific HER2 mutations.

While lung cancer is common, these molecularly defined patient populations can be relatively rare. HER2-mutated tumors account for a small percentage of NSCLC cases and occur more frequently in people who have never smoked.

Hyrnuo was initially approved in November 2025 as a second-line treatment. The new approval allows eligible patients to receive it earlier in their treatment.

The decision also uses the FDA's accelerated approval pathway, which can allow therapies to reach patients based on earlier measures of potential benefit while confirmatory studies are underway.

Bayer is conducting a Phase 3 trial, SOHO-02, comparing sevabertinib with standard therapy in the first-line setting. Those results will help determine whether the drug ultimately becomes a standard treatment for this patient population.

Looking Ahead

Two additional FDA decisions are expected September 19.

Ultragenyx's UX111 for MPS IIIA, or Sanfilippo syndrome type A, and IntraBio's Aqneursa for ataxia-telangiectasia both have PDUFA dates that day.

The decisions will be closely watched by patients, families, physicians, and the broader rare disease community.

The CheckRare Brief will continue to follow these developments and connect the dots across the rare disease landscape.

References

Ultragenyx Announces Phase 3 Aspire Results in Angelman Syndrome
https://www.globenewswire.com/news-release/2026/09/02/3355481/20739/en/ultragenyx-announces-phase-3-aspire-results-in-angelman-syndrome.html
New HAE Drugs for Acute and Prophylactic Therapies
https://firstwordpharma.com/story/7961829
FDA Grants Accelerated Approval to Sevabertinib for Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer
https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sevabertinib-locally-advanced-or-metastatic-non-squamous-non-small

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Living with Fabry disease can involve much more than managing the underlying disease. Patients may experience chronic pain, fatigue, headaches, cognitive concerns, hearing difficulties, and complications involving the heart and kidneys. Coordinating care among multiple specialists can add another layer of complexity.

In this episode, Staci Kallish, DO, Associate Professor of Clinical Medicine at the Perelman School of Medicine at the University of Pennsylvania, and Dawn Laney, MS, CGC, CCRC, Genetic Counselor and Program Leader of the Lysosomal Storage Disease Center at Emory University School of Medicine, discuss the real-world challenges faced by people living with Fabry disease.

The conversation features candid patient perspectives on four key areas of Fabry care:

• Managing symptoms: Why neuropathic pain, abdominal pain, headaches, fatigue, and other persistent symptoms may require approaches beyond Fabry-specific therapy.
• Managing cardiac and stroke risk: Why routine tests may not always provide the full picture and how experienced Fabry specialists can work with local cardiologists and other providers.
• Protecting kidney health: The importance of distinguishing Fabry-related kidney disease from other kidney problems and ensuring that nephrologists understand the unique risks associated with Fabry disease.
• Coordinating a multidisciplinary care team: How a “quarterback” or medical home can help connect geneticists, cardiologists, nephrologists, primary care physicians, and other specialists.
Drs. Kallish and Laney also discuss the importance of recognizing invisible symptoms, understanding individual pain triggers, using recommended schedules of assessments, accessing therapies closer to home, and taking advantage of patient advocacy and financial assistance resources.

For patients and families living with Fabry disease, the message is clear: effective care requires more than treating the disease—it requires understanding the person living with it.

This educational program is a non-CME activity made possible by an unrestricted grant from Amicus Therapeutics.

Produced by CheckRare. 

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.

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 of The CheckRare Brief, we discuss two recent FDA approvals for rare diseases, including Zanvastro for Alexander disease and Besremi for essential thrombocythemia (ET). We also examine a new gene therapy application for Huntington’s disease and what it could mean for patients with this devastating inherited disorder.

The FDA has approved Zanvastro, the first drug indicated to treat patients with Alexander disease, an extremely rare and progressive neurological disorder affecting approximately 1 to 3 people per million. The disease is caused by mutations in the GFAP gene that result in abnormal GFA protein accumulation in brain cells. Zanvastro is designed to reduce production of this abnormal protein. The approval was based on data from 49 patients, along with additional data from an open-label extension study. Ionis Pharmaceuticals also received a Rare Pediatric Disease Priority Review Voucher, which can provide priority review for a future FDA application and can have significant financial value.

The FDA also approved Besremi for adults with essential thrombocythemia (ET), a rare blood disorder in which the bone marrow produces too many platelets. This can increase the risk of blood clots and abnormal bleeding. Besremi is an interferon-based therapy that reduces abnormal platelet production and is already approved for polycythemia vera. Expanding an existing therapy into additional rare diseases is an increasingly common strategy in drug development, allowing companies to build on existing clinical and safety data while potentially reaching new patient populations.

Another important development involves Huntington’s disease, a devastating inherited neurological disorder caused by a mutation in the HTT gene. Symptoms typically emerge in adulthood and can include progressive movement problems, as well as cognitive, psychological, and behavioral changes. uniQure has submitted a Biologics License Application ( BLA), to the FDA for its gene therapy candidate. The submission follows extensive discussions between uniQure and the FDA, with the agency ultimately agreeing that existing three-year data could support a BLA under the accelerated-approval pathway. The application now moves into the formal FDA review process, making this an important development to watch for patients and families affected by Huntington’s disease.

Together, these developments highlight several important trends in rare disease drug development—from new approaches for extremely rare genetic disorders, to expanding existing therapies into additional indications, to the growing potential of gene therapy. As researchers continue to better understand the biology of rare diseases, these approaches could open new possibilities for patients who have historically had few treatment options.

References
FDA approved Zanvastro for Alexander disease
https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-alexander-disease 
FDA approved Besrimi for essential thrombocythemia
https://checkrare.com/fda-approves-besremi-for-treatment-of-adults-with-essential-thrombocythemia/
Uniqure submits BLA with the FDA for a gene therapy for Huntington's disease
https://www.uniqure.com/investors-media/press-releases



Produced by CheckRare.

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.

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 of The CheckRare Brief, we discuss two recent FDA approvals for rare diseases, including Zanvastro for Alexander disease and Besremi for essential thrombocythemia (ET). We also examine a new gene therapy application for Huntington’s disease and what it could mean for patients with this devastating inherited disorder.

The FDA has approved Zanvastro, the first drug indicated to treat patients with Alexander disease, an extremely rare and progressive neurological disorder affecting approximately 1 to 3 people per million. The disease is caused by mutations in the GFAP gene that result in abnormal GFA protein accumulation in brain cells. Zanvastro is designed to reduce production of this abnormal protein. The approval was based on data from 49 patients, along with additional data from an open-label extension study. Ionis Pharmaceuticals also received a Rare Pediatric Disease Priority Review Voucher, which can provide priority review for a future FDA application and can have significant financial value.

The FDA also approved Besremi for adults with essential thrombocythemia (, or ET), a rare blood disorder in which the bone marrow produces too many platelets. This can increase the risk of blood clots and abnormal bleeding. Besremi is an interferon-based therapy that reduces abnormal platelet production and is already approved for polycythemia vera. Expanding an existing therapy into additional rare diseases is an increasingly common strategy in drug development, allowing companies to build on existing clinical and safety data while potentially reaching new patient populations.
Another important development involves Huntington’s disease, a devastating inherited neurological disorder caused by a mutation in the HTT gene. Symptoms typically emerge in adulthood and can include progressive movement problems, as well as cognitive, psychological, and behavioral changes. uniQure has submitted a Biologics License Application (, or BLA), to the FDA for its gene therapy candidate. The submission follows extensive discussions between uniQure and the FDA, with the agency ultimately agreeing that existing three-year data could support a BLA under the accelerated-approval pathway. The application now moves into the formal FDA review process, making this an important development to watch for patients and families affected by Huntington’s disease.
Together, these developments highlight several important trends in rare disease drug development—from new approaches for extremely rare genetic disorders, to expanding existing therapies into additional indications, to the growing potential of gene therapy. As researchers continue to better understand the biology of rare diseases, these approaches could open new possibilities for patients who have historically had few treatment options.

References
FDA approved Zanvastro for Alexander disease

https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-alexander-disease

FDA approved Besrimi for essential thrombocythemia
https://checkrare.com/fda-approves-besremi-for-treatment-of-adults-with-essential-thrombocythemia/

Uniqure submits BLA with the FDA for a gene therapy for Huntington's disease
https://firstwordpharma.com/story/7940898
https://www.uniqure.com/investors-media/press-releases

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