Nisha Joseph, MD, Associate Professor in the Department of Hematology and Medical Oncology at the Emory University School of Medicine, discusses how bispecific antibodies are changing multiple myeloma treatment. 

Multiple myeloma is a rare cancer of the plasma cells and the most common type of plasma tumor. Plasma cells are white blood cells that make antibodies to protect against infection. In multiple myeloma, these cells multiply rapidly, crowding out normal cells in the bone marrow and affecting the production of red blood cells, platelets, and other white blood cells. Symptoms include bones that break easily, frequent infections, fatigue, bruising, and bleeding. About 36,000 Americans are diagnosed with multiple myeloma each year.

Multiple myeloma is challenging to treat. Between 30% and 50% of patients don’t respond to first-line therapy, and almost everyone who initially achieves remission relapses or develops resistance over time. Because of this, researchers are always looking for new ways to combat the disease. 

Dr. Joseph said that bispecific antibodies are especially promising because they help a patient’s T cells recognize and attack the cancer. She described the process in simple terms. “It basically gloms onto the T cell, gloms onto the myeloma cell, and says, ‘Hey, look over here. Kill this guy.’” 

Furthermore, Dr. Joseph shared that bispecific antibodies can be combined with other myeloma drugs because they fight cancer in different ways. For example, some drugs, such as immunomodulatory agents and cereblon E3 ligase modulatory drugs (CELMoDs), stimulate the immune cells, while bispecific antibodies direct T cells to attack myeloma directly. Researchers are trying to determine whether combining these treatments can improve patient outcomes. 

Despite their potential benefits, Dr. Joseph said that undergoing bispecific antibody treatment requires short-term and long-term considerations. 

In the short term, bispecific antibodies are typically administered via a ramp-up period that takes about a week. Initial doses are small, but they increase over time, and that process requires several doctor visits. Dr. Joseph shared that this approach reduces the risk of cytokine release syndrome (CRS), which can cause fever, low blood pressure, and shortness of breath. Some patients may also experience neurological symptoms, which can require caregiver support.

The good news is that after the initial ramp-up period, Dr. Joseph said these side effects generally become much less of a concern.  

In the long term, bispecific antibodies can increase the risk of infection and low blood counts. Dr. Joseph noted that clinicians have learned that when it comes to using these drugs, “less is more.” She then explained that once a patient responds to treatment, doctors typically extend the time between doses to make it easier on the immune system. Preventive measures, such as antibody infusions and antibiotics, can also support these efforts.

Next, Dr. Joseph emphasized the importance of putting patients first when using bispecific antibodies. Even though these drugs are effective and typically well-tolerated, treatment is an ongoing process, requiring routine visits, something she described as “a marathon, not a sprint.” 

Even so, these drugs make multiple myeloma treatment more accessible. Unlike CAR T-cell therapy, which is primarily offered at larger academic centers with the necessary infrastructure, bispecific antibodies can be administered at smaller facilities, like community treatment centers. 

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

To learn more about Dr. Joseph’s background and areas of expertise, visit: https://winshipcancer.emory.edu/profiles/joseph-nisha.php

0 0

In this episode, we discuss gambling on clinical trials, the FDA approval of a new formulation of Sjögren’s disease treatment, and an approval in IgA nephropathy.

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.

0 0

In this episode, we discuss gambling on clinical trials, the FDA approval of a new formulation of Sjögren’s disease treatment, and an approval in IgA nephropathy.

0 0

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

0 0

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

2 0

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

SPS and gMG are rare neurological and neuromuscular disorders:

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

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

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

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

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

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

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

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

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

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

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

0 0

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

0 0

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

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

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

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

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

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

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

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

The pooled data showed improvements in several areas, including:

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

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

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

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

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

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

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

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

Rare Discussions is produced by CheckRare, the leading multimedia platform dedicated to advancing education, awareness, and innovation across the rare disease community.

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

Subscribe to the CheckRare Podcast Network for exper...

0 0

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

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

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

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

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

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

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

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

The pooled data showed improvements in several areas, including:

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

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

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

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

No treatment-related serious adverse events were identified.

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

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

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

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

1 0