August is SMA Awareness Month, a time dedicated to increasing understanding of spinal muscular atrophy (SMA) and supporting the individuals and families impacted by this rare genetic neuromuscular condition. SMA affects the motor neurons, causing progressive muscle weakness and loss of movement. Most SMA types are caused by mutations in the SMN1 gene, while extra copies of the SMN2 gene modify the severity of disease. Early diagnosis and ongoing specialized care can make a significant difference in patient outcomes.

SMA has undergone a remarkable transformation over the past decade, with advances in disease-modifying therapies fundamentally improving muscle strength, patient mobility, and quality of life in persons living with this condition. However, many patients continue to face disease-related challenges that need to be recognized.

SMA Awareness Month is an opportunity to recognize the importance of continued research, multidisciplinary care, patient advocacy, and education within the rare disease community.

At CheckRare, we are committed to raising awareness of rare disorders like SMA and helping connect healthcare professionals and patients with timely educational resources, expert insights, and emerging clinical developments.

For insights on SMA from the Muscular Dystrophy Association (MDA) 2026 Clinical & Scientific Conference, visit https://checkrare.com/sma-in-focus-practical-insights-from-mda-2026/

To learn more about the development of Itvisma gene therapy for SMA, visit https://checkrare.com/itvisma-gene-therapy-for-patients-with-spinal-muscular-atrophy/

To learn about the changing definition of success in the care and management of SMA, visit https://checkrare.com/spinal-muscular-atrophy-the-changing-definition-of-success/

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Pete Schmidt, MD, MSc, Chief Medical Officer of Portal Therapeutics, discusses data from the phase 2a GATEWAY trial testingPORT-77, an ABCG2 inhibitor, in patients with erythropoietic protoporphyria (EPP).

EPP is a rare congenital metabolic disorder characterized by an inborn error of porphyrin-heme biosynthesis. Signs and symptoms include painful cutaneous photosensitivity leading to blistering and scarring of the exposed skin areas, erythrodontia, red discoloration of urine, hemolytic anemia, and splenomegaly.

The phase 2a GATEWAY clinical trial (NCT06971900) was a blinded, randomized, placebo-controlled crossover trial evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamic effects on plasma protoporphyrin IX (PPIX) of PORT-77 in adults with EPP.

PORT-77 is a novel investigational oral, small molecule ABCG2 inhibitor designed to modify efflux of PPIX from the red blood cell to the plasma and from hepatocytes to the biliary tract.

A total of 19 patients enrolled and received placebo followed by 180 mg of PORT-77 oral suspension once daily (QD) or 300 mg twice daily (BID) for four days.

Results presented at the European Hematology Association (EHA) 2026 Congress highlighted the potential of PORT-77 in causing rapid, dose-dependent reductions in plasma PPIX. A mean decrease of 79% in plasma PPIX was observed in participants receiving 300 mg BID and 63% for those receiving 180 mg QD. These reductions were observed within hours of treatment in both dose groups with no rebound effect after dosing cessation. Additionally, these reduction rates were consistent across a broad range of baseline PPIX levels.

PORT-77 was well tolerated, with no serious adverse events, treatment discontinuations, or tolerability signals observed.

Based on these results, initiation of the global phase 2b/3 PATHWAY trial evaluating the safety and efficacy of PORT-77 in patients with EPP and XLP is expected in Q3 2026.

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

CHAPTERS
Introduction 00:00
EPP Overview 00:57
Diagnostic Journey 2:44
Signs and Symptoms 4:35
Current Management 5:19
PORT-77 Overview 7:47
GATEWAY Clinical Trial 9:38
Take Home Message 12:46

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Jim Herbert, a patient with ROS1-positive non-small cell lung cancer (NSCLC), discusses his diagnosis and treatment journey.

ROS1-positive NSCLC is a rare and aggressive lung cancer that typically occurs in patients aged 50 years and older and who have never smoked. Brain metastases are common in patients with this condition.

Mr. Herbert, a longtime ice hockey referee and coach, has always been healthy, active, and a lifelong non-smoker. However, in 2024, a cough that returned at the end of every hockey season caused a fractured rib, and scans found a mass in his lung. Additional biomarker testing later identified a highly rare ROS1 mutation, ultimately leading to a diagnosis of advanced ROS1-positive NSCLC.

Chemotherapy and surgery to remove part of his lung was started quickly and after his mutation was confirmed, he began targeted therapy Ibtrozi (taletrectinib), which he remains on today. Starting on this treatment allowed Mr. Herbert to get back on the ice and keep reffing.

His message to other patients is to stay positive and continue to believe, noting the importance of taking good care of yourself throughout treatment and beyond.

To learn more about ROS1-positive NSCLC and other rare cancers, visit https://checkrare.com/diseases/cancers/

CHAPTERS
Introduction 00:00
Diagnostic Journey 00:47
Treatment and Management 2:08
Returning to the Ice 6:16
Message to Other Patients 7:16

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Roberto Mina, MD, Assistant Professor at Winship Cancer Institute at Emory University, discusses results from the MajesTEC-9 and CARTITUDE-4 clinical trials in patients with relapsed/refractory multiple myeloma (RRMM).

MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to relapse and/or refractory to therapy.

CARTITUDE-4 Cytogenetic Subgroup Analysis

CARTITUDE-4 (NCT04181827) is a phase 3 randomized clinical trial comparing Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T Cell (CAR-T) therapy directed against BCMA, versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in patients with relapsed and lenalidomide-refractory MM.

Previous analyses of cilta-cel showed significant overall (OS) and progression-free survival (PFS) benefits of cilta-cel in patients with lenalidomide-refractory MM after 1 to 3 lines of therapy. The data presented at ASCO 2026 looked at the safety and efficacy in patients who received cilta-cel as study treatment with high- and standard-risk cytogenetics who responded to bridging therapy.

Of 176 total patients who received cilta-cel as study treatment, with a median follow-up, of 33.6 months, 64 patients had high-risk cytogenetics and achieved partial response or better to bridging therapy. In these patients, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 65.1% and 87.2%, respectively. In 40 patients with standard-risk cytogenetics and partial response or better to bridging therapy, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 85.0% and 92.5%, respectively.

Safety analysis included 64 patients with high-risk and 40 with standard-risk cytogenetics. In the high-risk subgroup, cytokine release syndrome was reported in 73.4% of patients, serious nonhematological adverse events in 64.1%, grade 3/4 infections in 43.8%, and immune effector cell-associated neurotoxicity syndrome in 7.8%. Corresponding rates in the standard-risk subgroup were 70.0%, 57.5%, 30.0%, and 0. Nonrelapse mortality occurred in 9 patients and there were 4 infection-related deaths in the high-risk population. No cases of immune effector cell (IEC)-parkinsonism were reported in either subgroup.

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Roberto Mina, MD, Assistant Professor at Winship Cancer Institute at Emory University, discusses results from the MajesTEC-9 and CARTITUDE-4 clinical trials in patients with relapsed/refractory multiple myeloma (RRMM).

MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to relapse and/or refractory to therapy.

MajesTEC‑9 Phase 3 Results

MajesTEC-9 (NCT05572515) is a phase 3 randomized clinical trial comparing teclistamab monotherapy, a bispecific T-cell engager (BiTe) antibody, versus pomalidomide, bortezomib, dexamethasone (PVd) or carfilzomib, dexamethasone (Kd) in patients with relapsed or refractory MM who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.

A total of 593 patients were randomized and had a median follow-up of 17.3 months. Teclistamab was observed to significantly improve both progression free survival and overall survival versus PVd/Kd. Of 174 patients treated with PVd/Kd who received subsequent treatment, 68.4% received BsAb or CAR-T. Progression free survival favored teclistamab across all prespecified subgroups, including anti-CD38-refractory patients and len-refractory patients. Complete response or better rate was significantly higher with teclistamab versus PVd/Kd.

At data cutoff, 65.3% of patients remained on teclistamab versus 24.0% on PVd/Kd. Treatment emergent adverse events were similar for teclistamab and PVd/Kd. Grade 3/4 adverse events (84.9% vs 76.3%) and grade 5 adverse events (6.5% vs 3.5%) were higher with teclistamab vs PVd/Kd, noting the median treatment duration was 13.1 months with teclistamab 7.0 months with PVd/Kd. Treatment discontinuation lower with teclistamab versuss PVd/Kd. CRS occurred in 66.0% of pts with teclistamab and ICANS in 4.1%.

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Roberto Mina, MD, Assistant Professor at Winship Cancer Institute at Emory University, discusses results from the MajesTEC-9 and CARTITUDE-4 clinical trials in patients with relapsed/refractory multiple myeloma (RRMM).

MM is a rare blood cancer characterized by the expansion of malignant plasma cells in the bone marrow associated with excessive production of monoclonal immunoglobulins in blood and urine. Individuals with multiple myeloma develop significant osteolytic bone lesions and have immunodeficiency that compromise their longevity and quality of life. The exact underlying cause of disease is currently unknown. Most patients with MM require multiple lines of therapy as patients are prone to relapse and/or refractory to therapy.

MajesTEC‑9 Phase 3 Results

MajesTEC-9 (NCT05572515) is a phase 3 randomized clinical trial comparing teclistamab monotherapy, a bispecific T-cell engager (BiTe) antibody, versus pomalidomide, bortezomib, dexamethasone (PVd) or carfilzomib, dexamethasone (Kd) in patients with relapsed or refractory MM who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.

A total of 593 patients were randomized and had a median follow-up of 17.3 months. Teclistamab was observed to significantly improve both progression free survival and overall survival versus PVd/Kd. Of 174 patients treated with PVd/Kd who received subsequent treatment, 68.4% received BsAb or CAR-T. Progression free survival favored teclistamab across all prespecified subgroups, including anti-CD38-refractory patients and len-refractory patients. Complete response or better rate was significantly higher with teclistamab versus PVd/Kd.

At data cutoff, 65.3% of patients remained on teclistamab versus 24.0% on PVd/Kd. Treatment emergent adverse events were similar for teclistamab and PVd/Kd. Grade 3/4 adverse events (84.9% vs 76.3%) and grade 5 adverse events (6.5% vs 3.5%) were higher with teclistamab vs PVd/Kd, noting the median treatment duration was 13.1 months with teclistamab 7.0 months with PVd/Kd. Treatment discontinuation lower with teclistamab versuss PVd/Kd. CRS occurred in 66.0% of pts with teclistamab (Gr and ICANS in 4.1%.

CARTITUDE-4 Cytogenetic Subgroup Analysis
CARTITUDE-4 (NCT04181827) is a phase 3 randomized clinical trial comparing Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T Cell (CAR-T) therapy directed against BCMA, versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in patients with relapsed and lenalidomide-refractory MM.

Previous analyses of cilta-cel showed significant overall (OS) and progression-free survival (PFS) benefits of cilta-cel in patients with lenalidomide-refractory MM after 1 to 3 lines of therapy. The data presented at ASCO 2026 looked at the safety and efficacy in patients who received cilta-cel as study treatment with high- and standard-risk cytogenetics who responded to bridging therapy.

Of 176 total patients who received cilta-cel as study treatment, with a median follow-up, of 33.6 months, 64 patients had high-risk cytogenetics and achieved partial response or better to bridging therapy. In these patients, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 65.1% and 87.2%, respectively. In 40 patients with standard-risk cytogenetics and partial response or better to bridging therapy, median progression free survival and overall survival were not reached, however, 30-month progression free survival and overall survival rates were 85.0% and 92.5%, respectively.

Safety analysis included 64 patients with high-risk and 40 with standard-risk cytogenetics. In the high-risk subgroup, cytokine release syndrome was reported in 73.4% of patients, serious nonhematological adverse events in 64.1%, grade 3/4 infections in 43.8%, and immune effector cell-associated neurotoxicity syndrome in 7.8%. Corresponding rates in the standard-risk subgroup were 70.0%, 57.5%, 30.0%, and 0. Nonrelapse mortality occurred in 9 patients and there were 4 infection-related deaths in the high-risk population. No cases of immune effector cell (IEC)-parkinsonism were reported in either subgroup.

CHAPTERS
Introduction 00:00
Unmet Needs in Multiple Myeloma 00:31
MajesTEC-9 Clinical Trial 2:04
CARTITUDE-4 Clinical Trial 5:12
T-Cell Directed Therapies in the Treatment Journey 7:26
Impact on Clinical Practice and Patient Outcomes 8:46

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David Kuter, MD, DPhil, Director of Clinical Hematology at Massachusetts General Hospital and Professor of Medicine at Harvard Medical School, discusses cognitive impairment in patients with immune thrombocytopenia (ITP).

ITP is an autoimmune bleeding disorder characterized by too few platelets in the blood. Symptoms may include bruising, nosebleeds or bleeding in the mouth, bleeding into the skin, and abnormally heavy menstruation. It has been traditionally managed with corticosteroids, medicines that stimulate the bone marrow to increase platelets, and immunoglobulin infusions to restore critically low platelet counts.

Data presented at the European Hematology Association (EHA) 2026 meeting highlights that focusing on platelet counts alone does not fully capture the disease burden of ITP. The objective of the study was to determine the frequency, nature, and severity of cognitive impairment in chronic primary ITP in a real-world setting.

Of 104 patients screened, 97 were eligible to participate in the study and completed the Cognitive Brief Battery (CBB) test, a validated test evaluating psychomotor function, visual attention, visual learning, and visual working memory. The median duration of ITP was 10 years. 82 patients reported receiving active ITP treatment at index, including TPO-RAs, corticosteroids, other immunosuppressants, fostamatinib, rituximab, and/or other. Median platelet count was 143×109/L and median hemoglobin was 139 g/L. 80 participants had comorbidities, including arterial hypertension, anxiety, obesity, depression, and hypercholesterolemia. The mean ITP bleeding scale total score was 0.04 and mean scores for FACIT-Fatigue, ITP-PAQ psychological health (PH), and ITP-PAQ overall QOL were 37, 76, and 65, respectively.

Clinically important cognitive impairment was observed in 26% of patients, with 68% aged less than 65 years. Among the 97 patients evaluated, 7 patients, ages 39-78 years, had z-score of less than or equal to -1 for both composite scores; 12 patients, aged 25-75 years, had z-score of less than or equal to -1 for learning/working memory only, and 6 patients, aged 25-80 years, had z-scores of less than or equal to -1 for psychomotor function/attention only.

Overall, the analyses showed that patients continue to experience persistent fatigue and cognitive impairment even with stable platelet counts. This highlights the need for more comprehensive disease management in ITP that focuses more on a patient's quality of life beyond hematologic lab results.

CHAPTERS
Introduction 00:00
Looking Beyond Platelet Counts 00:51
Cognitive Impairments in ITP 2:15
Fatigue in ITP 3:35
Underlying Immune Dysfunction 5:09
Better Assessment of These Symptoms 6:32
Comprehensive Disease Control 7:44

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Joanne Quan, MD, Chief Medical Officer of Mirum Pharmaceuticals, discusses results from the PROGRESS study of zilurgisertib in patients with fibrodysplasia ossificans progressiva (FOP).

FOP is a disorder in which skeletal muscle and connective tissue are gradually ossified. This condition leads to bone formation outside the skeleton that restricts movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and moving down the body and into the limbs. People with FOP are born with abnormal big toes which can be helpful in making the diagnosis. Trauma, such as a fall or invasive medical procedure, or a viral illness may trigger episodes of muscle swelling and inflammation. These flareups last for several days to months and often result in permanent bone growth in the injured area. FOP is almost always caused by a genetic change at the same place in the ACVR1 gene.

Phase 2 results from Cohort 1 of the PROGRESS study (NCT05090891) evaluating zilurgisertib in adolescents and adults with FOP were presented at the ENDO 2026 annual meeting. Zilurgisertib is an investigational oral activin receptor-like kinase 2 (ALK2) inhibitor.

Of 63 patients who received one dose of zilurgisertib (n = 32) or placebo (n = 31), 62 enrolled in the extension. The primary endpoint was the proportion of patients with new heterotopic ossification (HO) lesions on whole-body CT scan at week 24.

At week 24, there was an 81.2% reduction in patients with new lesions receiving zilurgisertib versus 16.7% receiving placebo. Total new lesion volume decreased by 99.6% with zilurgisertib, while placebo was associated with a marked increase. The mean annualized total number of new flares was also lower for zilurgisertib.

In the open-label period, no new lesions were reported regardless of treatment assignment. From week 24-48, mean decreases in total volume of all HO lesions were observed in both zilurgisertib-randomized and crossover patients. The mean number of annualized new flares was low for both patient groups.

The most common adverse events in the zilurgisertib group were FOP flare-up or aching/pain due to FOP, headache, upper respiratory tract infection, arthralgia, epistaxis, and nausea, with a similar profile in the extension. Most adverse events were mild or moderate and none led to dose reduction or discontinuation with zilurgisertib across both periods.

CHAPTERS
Introduction 00:00
FOP Overview 00:10
Zilurgisertib Overview 1:38
PROGRESS Clinical Trial 2:24
What Physicians Should Know 6:05

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Robert Hal Scofield, MD, Professor of Medicine, at the University of Oklahoma and Oklahoma Medical Research Foundation, discusses the DAHLIAS clinical trial evaluating nipocalimab in Sjögren’s disease (SjD).

SjD is an autoimmune disorder that largely impacts secretory glands, such as those that produce tears and saliva. It is also associated with rheumatic disorders such as rheumatoid arthritis or systemic lupus erythematosus. Hallmark symptoms include dry mouth and dry eyes, but the condition may cause skin, nose, and vaginal dryness. SjD may also affect other organs of the body including the kidneys, blood vessels, lungs, liver, pancreas, and brain.

Nipocalimab is a monoclonal antibody, designed to block FcRn and reduce levels of circulating IgG antibodies. It is currently approved for the treatment of generalized myasthenia gravis.


At the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress new biomarker exploratory analyses from the DAHLIAS phase 2 study (NCT04968912) evaluating nipocalimab in SjD was presented.

Results included clinical improvements observed across all patients. The most significant responses were observed in patients with elevated known disease-driving autoantibodies and IgG levels. Patients in the autoantibody-high subgroup who were treated with nipocalimab achieved higher response rates than the overall population, at 62.5% versus 51.9%. Previously reported results demonstrated statistically significant improvement in ClinESSDAI scores with nipocalimab versus placebo.

Nipocalimab is being further evaluated in patients with systemic SjD in the ongoing DAFFODIL phase 3 clinical trial (NCT06741969).

CHAPTERS
Introduction 00:00
Sjögren’s Disease Overview 00:53
Key Findings From DAHLIAS Clinical Trial 2:01
Stronger Responses in Autoantibody Subgroups 3:34
Identifying Patients Who Will Benefit 4:48
Next Steps 5:22
Take Home Message 6:46

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