Michael J. Thorpy, MD, Professor of Neurology at Albert Einstein College of Medicine, discusses positive results in study of Lumryz (sodium oxybate) for hallucinations in patients with narcolepsy.

Narcolepsy is a chronic neurological disorder characterized by an inability of the brain to control sleep-wake cycles. Patients with narcolepsy typically enter REM sleep more quickly, causing the boundaries between wakefulness and sleep to blur. This causes fragmented sleep at night as well as muscle weakness and dream activity while awake. Common symptoms include excessive daytime sleepiness, cataplexy, sleep paralysis, and hallucinations.

Dr. Thorpy explains the prevalence of hypnagogic hallucinations in patients with narcolepsy as a result of entering REM sleep so quickly. Patients may experience REM dream phenomena while still awake or asleep. These dream hallucinations are often unpleasant and frightening and may include vivid dreams, lucid dreams, and out-of-body experiences.

Lumryz is an extended-release central nervous system depressant and new formula of sodium oxybate indicated for the treatment of cataplexy and excessive daytime sleepiness in patients ages 7 years and older with narcolepsy. The treatment may also help correct REM mechanisms that affect REM sleep phenomena.

Data was recently presented at the SLEEP 2025 meeting on the effects of Lumryz on hallucinations in patients with narcolepsy. The study was a 13-week, double-blind, placebo controlled trial and results were presented from a post-hoc analysis. Over 12,000 hallucination episodes were recorded throughout the study. Lumryz illustrated about a 50% reduction in hallucinations compared to placebo. The most improved hallucinations were those considered frightening and that occurred at sleep onset.

Chapters:
Introduction 00:00
Hallucinations in Narcolepsy 00:47
Treatment Strategies 3:14
Lumryz Overview 5:37
SLEEP 2025 Presentations 7:59
Take Home Message 10:40

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Fadi Fakhouri, MD, PhD, Professor of Nephrology at CHUV Lausanne, Switzerland, discusses new data on pegcetacoplan in patients with C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN).

C3G is a rare kidney disease characterized by damage to kidney glomeruli due to abnormal activation of the complement system. When C3 proteins get lodged in the kidney, glomeruli get injured and buildup of toxins and reduced urine production occur. This can ultimately lead to declined kidney function. Common signs and symptoms include hematuria, proteinuria, reduced glomerular filtration rate and increased creatinine levels, fatigue, and edema of the hands, feet, and ankles.

Pegcetacoplan is a targeted C3 therapy designed to regulate excessive activation of the complement cascade. It is currently approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

The VALIANT (NCT05067127) clinical trial is a phase 3, randomized, placebo-controlled, double-blind, multicenter study evaluating the safety and efficacy of pegcetacoplan in patients ages 12 years and older with C3G or primary IC-MPGN. A total of 124 patients were enrolled and randomized to pegcetacoplan or placebo twice weekly for 26 weeks. Following the 26-week period, an open-label phase was open to all patients. The primary endpoint was log transformed ratio of urine protein-to-creatinine (UPCR) at week 26 compared to baseline.

Recently, new data from this trial was presented at the 2025 European Renal Association (ERA) Congress. Pegcetacoplan demonstrated a statistically significant proteinuria reduction of 68% at week 26 versus placebo. This reduction was sustained at one year. Patients also achieved stabilization of kidney function measured by estimated glomerular filtration rate (eGFR). For patients that switched to pegcetacoplan from placebo during the open-label extension, similar results were seen in proteinuria reduction and kidney function stabilization. Additionally, the safety profile of pegcegtacoplan was favorable.

Chapters:
Introduction 00:00
C3G Overview 00:40
Current Management 2:00
Pegcetacoplan Overview 3:02
VALIANT Clinical Trial 3:43
Take Home Message 7:57
Kidney Transplantation 8:57

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Mike Flanagan, PhD, Chief Scientific Officer at Avidity Biosciences, discusses topline results from study testing delpacibart braxlosiran (del-brax) in patients with facioscapulohumeral muscular dystrophy and the newly initiated phase 3 trial.

FSHD is a rare disorder characterized by muscle weakness and atrophy. This condition gets its name from the areas of the body that are affected most often: muscles in the face, around the shoulder blades, and in the upper arms. The signs and symptoms of FSHD usually appear in adolescence and include loss of muscle function, pain, and fatigue. The condition is caused by abnormal expression of the DUX4 gene.

Del-brax is a monoclonal transferrin receptor 1 (TfR1) antibody conjugated with a siRNA targeting DUX4 mRNA, designed to target the underlying cause of abnormal DUX4 gene expression.

The FORTITUDE clinical trial program includes a phase 1/2, randomized, placebo-controlled, double-blind study evaluating multiple doses of del-brax in patients with FSHD. In total, the two dose escalation cohorts evaluated 39 patients on either 2 mg/kg or 4 mg/kg of del-brax versus placebo over 12 months.

Top line data from this trial showed consistent improvement of functional mobility and muscle strength measured by the 10-Meter Walk-Run test, Timed Up and Go, and quantitative muscle testing compared to placebo. There was also an observed consistent improvement in multiple measures of quality of life with del-brax versus placebo measured by patient reported outcomes. Additionally, rapid and significant reductions in KHDC1L and creatine kinase levels were observed. Del-brax is illustrating a favorable long-term safety and tolerability profile with most adverse events mild to moderate.

Based on these results, del-brax has been granted access to the Accelerated Approval Program for the treatment of FSHD by the U.S. Food and Drug Administration (FDA). To move forward with a full approval, the global, confirmatory, randomized, placebo-controlled, double-blind, 18-month, phase 3 FORWARD study has been initiated. The study will evaluate 2 mg/kg of del-brax every six weeks in approximately 200 patients with FSHD.

Chapters:
Introduction 00:00
FSHD Overview 00:48
Current Management 4:11
Del-brax Overview 4:38
FORTITUDE Clinical Trial Data 5:43
Next Steps 6:56
Other Programs 8:14

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Paolo Ghia, MD, PhD, Professor of Medical Oncology at Università Vita-Salute San Raffaele in Milan, Italy, discusses results from clinical trial testing ibrutinib plus venetoclax in patients with chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL).

CLL/SLL are rare cancers that affect the white blood cells, specifically B cells. The conditions are similar but differ primarily in location of the disease. In patients with CLL, the cancer mainly manifests in the bloodstream, while in patients with SLL, the cancer manifests mainly in the lymph nodes and lymphoid tissue. Early signs and symptoms may include swollen lymph nodes, fatigue, weight loss, fever, night sweats and/or frequent infections. The underlying cause is thought to be a combination of genetic and other unknown factors.

Ibrutinib is a tyrosine kinase inhibitor and venetoclax is a B-cell lymphoma 2 protein inhibitor, both approved for the treatment of CLL. The combination Ibr+Ven is an oral, once-daily, chemotherapy-free first-line treatment for CLL/SLL. The CAPTIVATE clinical trial (NCT02910583) was a phase 2, multicenter, 2-cohort study evaluating ibrutinib plus venetoclax (Ibr+Ven) for the treatment of treatment-naïve patients with CLL/SLL. The trial specifically looked at minimal residual disease (MRD)-guided discontinuation and fixed duration therapy.

A total of 202 patients enrolled in this clinical trial and completed dosing with Ibr+Ven with a median follow-up of 68.9 months. The 5.5-year progression-free survival (PFS) rate was 66% and the overall survival (OS) rate was 97%. The 5.5-year PFS rates in patients without and with del(17p)/mutated TP53 were 70% and 36%, respectively. In patients with unmutated IGHV, 5.5-year PFS was 55%; 63% in patients without, and 44% in patients with concomitant del(17p)/mutated TP53/complex karyotype.For those with mutated IGHV, PFS was 79%, 85% in patients without, and 62% in patients with concomitant del(17p)/mutated TP53/complex karyotype.

Undetactable MRD (uMRD) was achieved in peripheral blood in 54% of patients at cycle 7 and 69% at end of treatment. This was also achieved in bone marrow in 69% of patients at the end of treatment. In patients with uMRD in peripheral blood at the end of treatment, 5.5-year PFS rates were higher than in those with MRD. A total of 64 patients had progressive disease following treatment with Ibr+Ven, while freedom from next-line treatment was 73%.
Of the 40 patients with available samples at disease progression, only one was found to have an acquired subclonal mutation in BCL2, a finding of unclear clinical significance. Importantly, no acquired resistance-associated mutations were observed in BTK or PLCG2. A total of 36 patients went on to receive retreatment, with 25 receiving ibrutinib alone and 11 receiving Ibr+Ven. Among those retreated with Ibr alone, the overall response rate (ORR) was 76% following a median follow-up of 28.4 months. The two-year PFS and OS rates in this group were 91% and 96%, respectively. For those retreated with Ibr+Ven, the ORR was 82% after a median follow-up of 15.2 months. Notably, both one-year PFS and OS rates in this group were 100%, highlighting the promising activity and tolerability of Ibr-based retreatment strategies in patients with CLL who experience disease progression.

Chapters:
Introduction 00:00
Current Treatment Options 00:38
CAPTIVATE Clinical Trial 1:46
Take Home Message 5:56

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Krish Patel, MD, Medical Oncologist at Sarah Cannon Research Institute, discusses first results from a study evaluating CAR-T cell therapy for large B cell lymphoma (LBCL).

LBCL is a form of non-Hodgkin lymphoma. Lymphomas occur when cells of the immune system, B lymphocytes, grow and multiply uncontrollably. It can start in the lymph nodes or outside of the lymphatic system in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain. Often, the first sign of is a painless rapid swelling in the neck, armpit, abdomen, or groin caused by enlarged lymph nodes. Other symptoms include night sweats, unexplained fevers, and weight loss.

First results from a global phase 1b study (NCT05421663) evaluating JNJ-90014496, a CD19/CD20 bispecific CAR-T cell therapy, in adult patients with relapsed/refractory LBCL was recently presented at the European Hematology Association 2025 meeting. Primary endpoints of the study are recommended phase 2 dose and safety. Secondary endpoints include objective response rate (ORR), complete response rate (CRR), time to first response, and pharmacokinetics.

As of February 2025, 48 patients with CAR-T naïve, heavily pretreated R/R LBCL were treated with JNJ-90014496. At a median follow-up of six months across all doses, 79% of patients cytokine release syndrome with median time to onset of three days and median duration of eight days. In 42 evaluable patients across all doses, ORR was 90.5% and CRR was 76.2%. Median time to first response was one month.

Grade 3/4 treatment emergent adverse events (TEAEs) were observed in 83% and 25% of patients, respectively. The most common grade 3/4 TEAEs were neutropenia, leukopenia, anemia, and thrombocytopenia.

The identified recommended phase 2 dose was 75M CAR+ T-cells. At this dose, in 20 evaluable patients with a median follow-up of three months, ORR was 95% and CRR was 80%.

At the identified recommended phase 2 dose, there were no grade 3/4 cytokine release syndrome, however 86% of patients had grade 1/2 cytokine release syndrome. Additionally, there were no grade 3/4 ICANS and only 5% of patients had grade 1 ICANS. At this dose, 77% had grade 3/4 TEAEs and 23% had serious TEAEs. The most common grade 3/4 TEAEs were neutropenia and lymphopenia.

Chapters:
Introduction 00:00
Large B Cell Lymphoma Landscape 00:32
CD19 Overview 1:28
Clinical Trial Overview 1:50
Take Home Message 6:02

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Neha Mehta-Shah, MD, Medical Oncologist at Washington University St. Louis, addresses quality-of-life concerns with cutaneous T-cell lymphoma.

CTCL is a rare group of malignancies that attack the body’s immune lymphatic system, affecting both B-cells and T-cells. Whereas the B-lymphocytes act to neutralize the pathogens, the main job of the T-lymphocytes is to attach to these foreign cells, viruses, or cancerous growths, and directly destroy them. The underlying cause of CTCL is not currently fully understood. Genetic causes are suspected but these issues appear sporadic and spontaneous in nature for the most common forms of CTCL.

The annual incidence of CTCL is 6.4 cases per 1 million people and the risk in men is twice the risk for women. The likelihood of disease increases with age with the median age at onset of 50 years. However, CTCL can affect children in rare cases.

Common symptoms include skin manifestations such as red, scaly patches that grow over time, severe pruritus, pain in affected areas, generalized lymphadenopathy, opportunistic infections, alopecia, and enlargement of liver or spleen.

Diagnosing CTCL can be challenging, leading to significant delays in diagnosis and subsequent treatment. This is often due to the variability in how patients present with the condition and its various subtypes.

There are a variety of treatment options available for CTCL. In addition to pharmacologic approaches, several other types of interventions have been used successfully, including radiation therapy, phototherapy, extracorporeal photopheresis, and in some cases, stem-cell transplant.

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Neha Mehta-Shah, MD, Medical Oncologist at Washington University St. Louis, discusses management options for cutaneous T-cell lymphoma.

CTCL is a rare group of malignancies that attack the body’s immune lymphatic system, affecting both B-cells and T-cells. Whereas the B-lymphocytes act to neutralize the pathogens, the main job of the T-lymphocytes is to attach to these foreign cells, viruses, or cancerous growths, and directly destroy them. The underlying cause of CTCL is not currently fully understood. Genetic causes are suspected but these issues appear sporadic and spontaneous in nature for the most common forms of CTCL.

The annual incidence of CTCL is 6.4 cases per 1 million people and the risk in men is twice the risk for women. The likelihood of disease increases with age with the median age at onset of 50 years. However, CTCL can affect children in rare cases.

Common symptoms include skin manifestations such as red, scaly patches that grow over time, severe pruritus, pain in affected areas, generalized lymphadenopathy, opportunistic infections, alopecia, and enlargement of liver or spleen.

Diagnosing CTCL can be challenging, leading to significant delays in diagnosis and subsequent treatment. This is often due to the variability in how patients present with the condition and its various subtypes.

There are a variety of treatment options available for CTCL. In addition to pharmacologic approaches, several other types of interventions have been used successfully, including radiation therapy, phototherapy, extracorporeal photopheresis, and in some cases, stem-cell transplant.

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Neha Mehta-Shah, MD, Medical Oncologist at Washington University St. Louis, provides an overview of cutaneous T-cell lymphoma (CTCL) and its diagnosis.

CTCL is a rare group of malignancies that attack the body’s immune lymphatic system, affecting both B-cells and T-cells. Whereas the B-lymphocytes act to neutralize the pathogens, the main job of the T-lymphocytes is to attach to these foreign cells, viruses, or cancerous growths, and directly destroy them. The underlying cause of CTCL is not currently fully understood. Genetic causes are suspected but these issues appear sporadic and spontaneous in nature for the most common forms of CTCL.

The annual incidence of CTCL is 6.4 cases per 1 million people and the risk in men is twice the risk for women. The likelihood of disease increases with age with the median age at onset of 50 years. However, CTCL can affect children in rare cases.

Common symptoms include skin manifestations such as red, scaly patches that grow over time, severe pruritus, pain in affected areas, generalized lymphadenopathy, opportunistic infections, alopecia, and enlargement of liver or spleen.

Diagnosing CTCL can be challenging, leading to significant delays in diagnosis and subsequent treatment. This is often due to the variability in how patients present with the condition and its various subtypes.

There are a variety of treatment options available for CTCL. In addition to pharmacologic approaches, several other types of interventions have been used successfully, including radiation therapy, phototherapy, extracorporeal photopheresis, and in some cases, stem-cell transplant.

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Neha Mehta-Shah, MD, Medical Oncologist at Washington University St. Louis, provides an overview of cutaneous T-cell lymphoma (CTCL), discusses management options, and addresses quality-of-life concerns.

CTCL is a rare group of malignancies that attack the body’s immune lymphatic system, affecting both B-cells and T-cells. Whereas the B-lymphocytes act to neutralize the pathogens, the main job of the T-lymphocytes is to attach to these foreign cells, viruses, or cancerous growths, and directly destroy them. The underlying cause of CTCL is not currently fully understood. Genetic causes are suspected but these issues appear sporadic and spontaneous in nature for the most common forms of CTCL.

The annual incidence of CTCL is 6.4 cases per 1 million people and the risk in men is twice the risk for women. The likelihood of disease increases with age with the median age at onset of 50 years. However, CTCL can affect children in rare cases.

Common symptoms include skin manifestations such as red, scaly patches that grow over time, severe pruritus, pain in affected areas, generalized lymphadenopathy, opportunistic infections, alopecia, and enlargement of liver or spleen.

Diagnosing CTCL can be challenging, leading to significant delays in diagnosis and subsequent treatment. This is often due to the variability in how patients present with the condition and its various subtypes.

There are a variety of treatment options available for CTCL. In addition to pharmacologic approaches, several other types of interventions have been used successfully, including radiation therapy, phototherapy, extracorporeal photopheresis, and in some cases, stem-cell transplant.

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