Rare Discussions

This accredited CME activity, led by David Kronn, MD, Associate Professor of Pathology and Pediatrics at New York Medical College, is the second module in a four-part curriculum focused on Best Practices for Explaining Newborn Screening Results to Parents. This module will focus on how to talk to parents about positive NBS results.

Supported by an educational grant from bluebird bio Inc. and Ultragenyx Pharmaceutical Inc.

To obtain CME credit, please go to https://checkrare.com/learning-center/courses/

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.

This accredited CME activity, led by Jerry Vockley, MD, PhD, Chief of Genetic and Genomic Medicine at the University of Pittsburgh, is the first module in a four-part curriculum focused on Best Practices for Explaining Newborn Screening Results to Parents. This module will provide clinicians with the fundamentals of newborn screening.

Supported by an educational grant from bluebird bio Inc. and Ultragenyx Pharmaceutical Inc.

To obtain CME credit, please go to https://checkrare.com/learning-center/courses/

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.

This accredited CME activity, led by Rachael Grace, MD, Associate Professor, Harvard Medical School, highlights the latest research about pyruvate kinase (PK) deficiency presented at ASH 2021 and provides expert analysis of its clinical relevance for busy members of the care team to help them care for patients they may encounter with this rare condition.

PK deficiency is a rare blood disease due to mutations in the PKLR gene that leads to decreased PK levels. Current therapies options are supportive (transfusions, iron chelation, splenectomy) but treatments are in development to better address the pathophysiology of this rare condition.

Supported by an educational grant from Agios Pharmaceuticals.

To obtain CME credit, please go to https://checkrare.com/learning-center/courses/

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.

Jeffrey A. Zonder, MD, Hematologist-Oncologist from the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan, describes the treatment landscape for patients with relapsed or refractory multiple myeloma.

Multiple myeloma is a rare blood cancer associated with uncontrolled growth of plasma cells. Abnormal plasma cells – also known as myeloma cells – interfere with the production of healthy blood cells in the bone marrow. Myeloma cells also produce inactive clones of abnormal antibodies that may negatively affect the bones and kidneys. Symptoms of multiple myeloma may include: bone pain (particularly in the chest and spine), frequent infections, weakness or numbness in the legs, fatigue, confusion, excessive thirst, and constipation. While the disease is treatable, relapses are common and some patients are refractory to first line therapy.

As Dr. Zonder explains, the treatment landscape for multiple myeloma is quickly developing and relatively promising compared to other cancer landscapes. However, these patients are still susceptible to relapse or becoming refractory to treatment. As such, there is a growing need for late line therapies for this patient population. CAR T-cell therapies have been investigated for relapsed or refractory multiple myeloma for a number of years. In March 2021, idecabtagene vicleucel (a CAR T-cell therapy) was approved by the U.S Food and Drug Administration for the treatment of patients with relapsed/refractory multiple myeloma who have received at least four prior lines of therapy. There are a few toxicity concerns associated with CAR T-cell therapies, the most notable of which is cytokine release syndrome, as well as accessibility issues. Bispecific antibody therapies are also being developed for multiple myeloma and have the potential to be a safe and effective alternative.

Dr. Zonder recently discussed data from the first-in-human study of REGN5458, a BCMA x CD3 bispecific antibody that is currently being investigated as a monotherapy for relapsed/refractory multiple myeloma patients (NCT03761108). Data from the phase 1 portion of this study were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

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.

Phillip Moreau, MD, PhD, Head of the Hematology Department at the University Hospital Phillip Moreau, MD, PhD, Head of the Hematology Department at the University Hospital Hôtel-Dieu, discusses the updated results from MajesTEC-1, a phase 1/2 study of teclistamab in relapsed/refractory multiple myeloma. These results were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

Multiple myeloma is a rare blood cancer. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.

As Dr. Moreau explains, MajesTEC-1 is a phase 1/2 study testing teclistamab in relapsed/refractory multiple myeloma. Teclistamab is a T-cell redirecting, bispecific IgG4 antibody that targets both B-cell maturation antigen (BCMA) and CD3 receptors to induce T-cell mediated cytotoxicity of BCMA-expressing myeloma cells. In this study, two cohorts were evaluated, one cohort given teclistamab weekly and one biweekly. Updated data on both of these cohorts was presented at the ASH 2021 meeting.

Response rates from both cohorts were encouraging with up to 75% of patients responding to treatment with teclistamab. As of the clinical cutoff, no new safety signals were identified in the phase 2 study. The most common nonhematologic AEs in all 159 patients treated at the recommended phase 2 dose were cytokine release syndrome, injection site erythema, and fatigue. The most common hematologic AEs were neutropenia, anemia, and thrombocytopenia.

According to Dr. Moreau, the take home message from this data is that teclistamab is a novel, tolerable, off-the-shelf agent that is immediately available. As a result, the use of teclistamab for advanced patients with BCMA may be approved fairly soon.

Longer follow-up of multiple myeloma patients receiving teclistamab is necessary.

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.

Drs. Ozlem Goker-Alpan and Swati Sathe discuss how our growing awareness of the central symptoms and comorbidities associated with many lysosomal storage diseases is changing how we manage these rare diseases.

This CME/CE activity is possible through an educational grant from Takeda, Cheisi, Ultragenyx Pharmaceuticals, and Spark Therapeutics.

To obtain credit for this activity, please visit https://checkrare.com/learning-center/courses/

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.

This accredited CME activity, led by Jonathan Bernstein, MD, Professor of Medicine at the University of Cincinnati, provides a summary of the latest information about hereditary angioedema (HAE) that was presented at the American College of Allergy, Asthma, & immunology 2021 Annual Scientific Meeting (ACAAI 2021). Since to the Covid-19 pandemic limited the ability for ACAAI members to commit fully to the 5-day event, this program provides a concise means to share the clinically relevant information presented at ACAAI 2021 with ACAAI members as well as other health care professionals who manage individuals with HAE.

HAE is a rare genetic disease that results in immunologic attacks that can be life threatening.

Supported by an educational grant from BioCryst.

To obtain CME credit, please go to https://checkrare.com/learning-center/courses/

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.

Paolo Ghia, MD, PhD, Professor at the Università Vita-Salute San Raffaele, Milan, Italy, discusses the updated, long-term data from the phase 2 CAPTIVATE study. This study evaluated ibrutinib plus venetoclax as a first-line treatment for chronic lymphocytic leukemia (CLL); data from this trial was recently presented at the American Society of Hematology Meeting & Exposition (ASH 2021).

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.

Jeffrey Neul, MD, PhD, Professor of Pediatrics at Vanderbilt University Medical Center, discusses recent top-line results from a phase 3 trial testing trofinetide to treat children with Rett syndrome.
Trofinetide is an analog of insulin-like growth factor 1 (IGF-1) and it is speculated that the orphan drug can restore homeostasis of neuronal signaling in diseases such as Rett syndrome.

​​Rett syndrome is a rare progressive neurodevelopmental condition that primarily affects girls. These girls appear to have normal psychomotor development during the first 6 to 18 months of life, followed by a developmental “plateau,” and then rapid regression in language and motor skills. Common symptoms include hand-wringing; fits of screaming and inconsolable crying; autistic features; panic-like attacks; bruxism; episodic apnea and/or hyperpnea; gait ataxia and apraxia; tremors; seizures; and slowed head growth. Rett syndrome is most commonly caused by a sporadic mutation in the MECP2 gene on the X chromosome. The majority of cases are not inherited from a parent.

Recently, positive top-line results from the Lavender study were announced. As Dr. Neul explains, the Lavender study (NCT04181723) is a phase 3 study evaluating the safety and efficacy of trofinetide in 187 Rett syndrome patients aged 5 to 20 years. Trofinetide met co-primary efficacy endpoints demonstrating statistically significant improvement over placebo in the Rett Syndrome Behaviour Questionnaire (RSBQ) and the Clinical Global Impression of Improvement (CGI-I). On the Rett Syndrome Behaviour Questionnaire (RSBQ), change from baseline to week 12 was -5.1 in the trofinetide arm vs. -1.7 in the placebo arm (P=.0175). The Clinical Global Impression–Improvement (CGI-I) score at week 12 was 3.5 vs. 3.8 (p=0.0030; effect size=0.47). The RSBQ is a caregiver assessment of the core symptoms of Rett syndrome and the CGI-I is a global physician assessment of worsening or improving Rett syndrome.

Additionally, trofinetide demonstrated a statistically significant separation over placebo on the key secondary endpoint, the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist–Social composite score (CSBS-DP-IT–Social) change from baseline to week 12 was -0.1 vs. -1.1 (P=.0064).

According to Dr. Neul, next steps following these results include two open-label extension studies as well as for the sponsor to organize a New Drug Admission (NDA) to the U.S. Food and Drug Administration. This NDA package is expected to be submitted some time this year.
For more information about Rett syndrome and other rare neurological disorders, visit checkrare.com/diseases/neurology

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.

Jeffrey A. Zonder, MD, hematologist-oncologist at the Barbara Ann Karmanos Cancer Institute in Detroit, Michigan, discusses data from the first-in-human study testing REGN5458 as a monotherapy for relapsed/refractory multiple myeloma patients (NCT03761108). Data from the phase 1 portion of this study were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

Multiple myeloma is a rare blood cancer associated with uncontrolled growth of plasma cells. While the disease is treatable, relapses are common and some patients are refractory to first line treatment.

As Dr. Zonder explains, REGN5458 is a BCMA x CD3 bispecific antibody that is currently being investigated in a phase 1/2 clinical trial. Data presented at ASH 2021 was related to the phase 1 portion of this study which is assessing the safety, tolerability, and dose-limiting toxicities (DLTs) of REGN5458 in patients with relapsed/refractory multiple myeloma as well as determining a recommended phase 2 dose regimen.

As of data cut-off (June 10, 2021), 68 patients were treated with REGN5458 in the dose escalation cohort with full doses ranging from 3–400 mg. Patients had a median of 5 prior lines of systemic therapy and the median duration of follow-up was 2.4 months.
Treatment-emergent adverse events (TEAE) were reported in 66 patients (97.1%), and Grade 3 or more TEAEs were reported in 52 (76.5%) patients. The most frequent TEAEs were fatigue in 29 patients (42.6%), and cytokine release syndrome (CRS) in 26 patients (38.2%). No patient had Grade 3 or more CRS or discontinued treatment due to CRS. There were no Grade 3 or more neurotoxicity events.

As Dr. Zonder notes, responses were observed at all dose levels and a maximally-tolerated dose was not reached at any level. Amongst patients treated at the 96 and 200 mg dose levels, the response rate was 73.3%. Across all dose levels, 92.6% of all responders achieved at least a very good partial response and 48.1% of responders had a complete response (CR) or stringent CR. Patients without extramedullary plasmacytomas responded more frequently than those with them. The Kaplan–Meier estimated median duration of response was not reached. The probability of duration of response ≥8 months was 92.1% with responses ongoing up to 19 months at the latest data cut-off.

Overall, REGN5458 continues to show an acceptable safety and tolerability profile as well as promising durable responses in triple- to penta-refractory patients with relapsed/refractory multiple myeloma.

To learn more about multiple myeloma and other rare cancers, visit checkrare.com/diseases/cancers/

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.