Rare Discussions

Arnon Kater, MD, PhD, Professor of Internal Medicine in the Faculty of Medicine at the University of Amsterdam discusses new data from the GLOW study of ibrutinib plus venetoclax (I+V) in elderly or unfit chronic lymphocytic leukemia (CLL) patients. The data were recently presented at The American Society of Hematology Meeting & Exposition (ASH 2021).

CLL is a rare blood cancer resulting in a build-up of lymphocytes in bone marrow, lymph nodes, and blood. The disease is considered treatable, but relapse is very common. Furthermore, many CLL patients cannot withstand the intensive chemotherapy needed to bring them into complete remission.

As Dr. Kater explains, the GLOW study (NCT03462719) is a phase 3 clinical trial evaluating the efficacy and safety of I+V in elderly or unfit CLL patients. In this trial, patients receiving I+V are compared to patients receiving chlorambucil plus obinutuzumab (C+O). The primary endpoint is progression-free survival and that data was presented earlier this year. Overall, it was found that risk of disease progression or death was reduced by approximately 78% in patients receiving I+V compared to those receiving C+O.

At ASH 2021, new data was presented looking at undetectable minimal residual disease (uMRD), which is an established predictive marker for PFS in CLL following chemoimmunotherapy. The new data demonstrate that the average rate of uMRD was significantly higher for I+V vs C+O in bone marrow (51.9% vs 17.1%) and in peripheral blood (54.7% vs 39.0%). Furthermore, sustainability of uMRD response between 3 and 12 months following end of treatment was measured; 80.4% of patients in the I+V cohort had sustained uMRD below 10-5 vs. 26.3% in the C+O cohort.

For more information about CLL 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.

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Anne Pariser, MD, Director of the NCATS’ Office of Rare Diseases Research (ORDR), provides an overview of the ORDR and the research they are involved with.

The ORDR is focused on multiple programs to improve the efficacy of rare disease research. Their two largest programs are the Rare Diseases Clinical Research Network (RDCRN) and the Genetic and Rare Diseases Information Center (GARD).

RDCRN provides support for clinical studies and facilitates collaboration, study enrollment and data sharing. Through the RDCRN consortia, researchers work with patient advocacy groups to study over 200 rare diseases at sites across the nation.

GARD provides the public with up-to-date health information on many rare diseases. It has a hotline that people (often parents) can call and ask questions about a particular rare disease.

Numerous other programs are led but the Office of Rare Diseases Research, including the annual “Rare Disease Day at NIH” event held the end of February.

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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.

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Drs. Ozlem Goker-Alpan and Uma Ramaswami discuss how the success of therapies to treat lysosomal storage disorders like Pompe disease, Gaucher disease, and various MPSs, has created phenotypes that previously did not exist.

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.

Alan Mendelsohn, MD, Chief Medical Officer at Timber Pharmaceuticals, gives an update on their congenital ichthyosis clinical trial.

Congenital ichthyosis is a rare genetic skin disorder characterized by dry, thickened, and scaling skin. Individuals with this condition may experience limited range in motion, chronic itching, an inability to sweat, and increased risk of infections. Currently, there is no approved targeted therapy for congenital ichthyosis. Symptom management for the condition is most often achieved with topical treatments (e.g., emollients, keratolytics, frequent baths, pumice stones) aimed at reducing the scaling and/or improving skin lubrication.

As Dr. Mendelsohn explains, for many years it has been known that retinoid therapy could play a crucial role in the treatment of congenital ichthyosis. The issue with retinoid therapies, particularly oral options, is their high toxicity when taken long-term. Timber Pharmaceuticals, with this in mind, developed a retinoid therapy that could be applied topically to reduce toxicity and hopefully allow congenital ichthyosis patients to use the therapy long-term.
The phase 2b CONTROL study was a randomized, double-blind, vehicle-controlled study designed to assess the efficacy and safety of two concentrations of TMB-001 (0.05% and 0.1% isotretinoin) for the treatment of two distinct subtypes of moderate-to-severe congenital ichthyosis (X-linked recessive and lamellar ichthyosis) in patients nine years old or older. Subjects applied TMB-001 twice daily for 12 weeks. The primary endpoint was the reduction of targeted ichthyosis severity, determined by a ≥50% reduction in the validated Visual Index for Ichthyosis Severity (VIIS) scaling score. Secondary endpoints included reduction in overall ichthyosis severity, as measured by a two-point improvement using the Investigator Global Assessment (IGA) scale. Topline results of this study showed reduction in targeted and overall severity of ichthyosis in patients in both treatment groups as measured by the VIIS scaling score and the IGA scale.

As Dr. Mendelsohn mentions, Timber Pharmaceuticals is planning for an end-of-Phase 2 meeting with the FDA in the beginning of 2022 and expects to start the Phase 3 study of TMB-001 in Q2 2022.

To learn more about congenital ichthyosis and other rare skin disorders, visit https://checkrare.com/diseases/skin-conditions/

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.

Alan Mendelsohn, MD, Chief Medical Officer at Timber Pharmaceuticals, gives a detailed overview of congenital ichthyosis.
As Dr. Mendelsohn explains, congenital ichthyosis is a rare genetic skin disorder characterized by dry, thickened, and scaling skin. Individuals with this condition may experience limited range in motion, chronic itching, an inability to sweat, and increased risk of infections. Congenital harlequin ichthyosis is a devastating subtype where skin over the entire body is thickened which can inhibit eating and breathing.
Dr. Mendelsohn also notes that there is no approved targeted therapy for congenital ichthyosis. Symptom management for the condition is most often achieved with topical treatments (e.g., emollients, keratolytics, frequent baths, pumice stones) aimed at reducing the scaling and/or improving skin lubrication.
To learn more about congenital ichthyosis and other rare skin disorders, visit https://checkrare.com/diseases/skin-conditions/

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.

Avanish Vellanki, Cofounder and CEO at Rain Therapeutics, discusses the role of p53 and MDM2 in cancers like liposarcoma, the mechanism of action of milademetan, and the positive pre-clinical data presented at the 2021 World Conference of Lung Cancer.

As Mr. Vellanki explains, p53 regulates the cell cycle and is essential for tumor suppression. MDM2 is a crucial regulator of p53. If MDM2 is overexpressed, p53 can be inactivated, leading to tumor growth and cancer progression. Milademetan, Rain Therapeutics’ lead product candidate, inhibits MDM2, and, in doing so, is hypothesized to reactivate p53 and thus control cancer growth in approximately 50% of cancers without a p53 mutation.

Mr. Vellanki notes that MDM2 inhibition has been studied for a number of years. However, in the past, blood toxicity has been an issue. One reason for that is previous treatment regimens would allow the drug to accumulate in the tissues of patients. Milademetan does not accumulate in tissues when patients take milademetan for 3 days and then no treatment for 11 days. This allows the drug to be effective but prevents blood toxicity. This dosing schedule, according to Mr. Vellanki, has led to triple-to-quadruple the length of progression free survival compared to standard of care in liposarcoma, milademetan’s main indication.

At the 2021 World Conference of Lung Cancer, pre-clinical data suggested milademetan could also be safe and effective in treating malignant pleural mesothelioma.

To learn more about liposarcoma 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.

Daniel Lovell, MD, MPH, Associate Director of the Division of Rheumatology at Cincinnati Children's Hospital Medical Center, gives an overview of juvenile idiopathic arthritis (JIA).

As Dr. Lovell explains, JIA is an umbrella term for a number of diseases in individuals under the age of 16 and characterized by chronic arthritis that persists for at least 6 weeks. There are currently seven recognized subsets of JIA. These include: systemic juvenile idiopathic arthritis, oligoarticular juvenile idiopathic arthritis (also known as oligoarthritis), rheumatoid factor positive polyarticular juvenile idiopathic arthritis (also known as polyarthritis, rheumatoid factor positive), rheumatoid factor negative polyarticular juvenile idiopathic arthritis (also known as polyarthritis, rheumatoid factor negative), psoriatic juvenile idiopathic arthritis, enthesitis-related juvenile idiopathic arthritis, and undifferentiated arthritis. All of these subtypes except systemic JIA are autoimmune conditions while systemic JIA is considered an autoinflammatory disease.

To learn more about JIA and other rare autoimmune/auto-inflammatory diseases, visit checkrare.com/diseases/autoimmune-auto-inflammatory

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 Gregory Grabowski discuss how new research into the pathophysiology of 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.

Roman Groisberg, MD, Medical Oncologist and Director of the Sarcoma Program at Rutgers Cancer Institute of New Jersey/RWJBarnabas Health, gives an overview of sarcomas.

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.

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Roman Groisberg, MD, Medical Oncologist and Director of the Sarcoma Program at Rutgers Cancer Institute of New Jersey/RWJBarnabas Health, discusses treatment options available for different sarcomas.

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.