A new hope for rare disease patients – Summary of orphan drug research and development in the last 2 months

In December 2021, the Menarini Group announced that the U.S. Food and Drug Administration (FDA) granted orphan drug designation (ODD) to their SEL24/MEN1703 for the treatment of Acute Myeloid Leukemia (AML).

SEL24/MEN1703 is a first-in-class, orally available, dual PIM/FLT3 inhibitor in-licensed by Menarini from Ryvu Therapeutics. It is an investigational compound not approved for use by regulatory agencies and currently investigated in the DIAMOND-01 trial as a single agent for the treatment of patients with relapsed/refractory AML.

DIAMOND-01 is a First-in-Human Phase I/II dose escalation and cohort expansion trial of SEL24/MEN1703, a monotherapy study in patients with relapsed/refractory AML. In the dose-escalation part of the DIAMOND-01 trial, SEL24/MEN1703 demonstrated a manageable safety profile up to the recommended dose of 125 mg/day, with initial evidence of anti-leukemic activity in a single agent setting. The results were then successfully replicated in the Phase II cohort expansion study. The same study also showed preliminary single-agent efficacy in relapsed/refractory AML, particularly in patients with IDH mutant disease, regardless of if the patients were naive to IDH inhibitors or previously exposed to IDH inhibitors.

The trial is currently recruiting AML patients with IDH1 or IDH2 mutations to further investigate the molecular activity of SEL24/MEN1703 in this molecularly defined subset of patients.

Elcin Barker Ergun, CEO of Menarini Pharmaceuticals Group, said, “FDA orphan drug designation represents an important milestone for SEL24/MEN1703 program. SEL24/MEN1703 is a first-in-class, orally available, dual PIM/FLT3 inhibitor that can contribute to finding new treatment paradigms for AML where significant unmet needs exist especially as resistance develops in later lines. We look forward to advancing the clinical development of SEL24/MEN1703 in AML with a goal to ultimately provide patients with a new therapeutic option for this hard-to-treat disease”

In the same month, Blade Therapeutics announced that the FDA had granted orphan drug designation to its Cudetaxestat for the potential treatment of systemic sclerosis (SSc).

Cudetaxestat is a non-competitive autotaxin inhibitor in clinical development for Idiopathic Pulmonary Fibrosis (IPF), with SSc being a similar fibriotic disease affecting approximately 100,000 people in the United States. SSc is a chronic, progressive autoimmune disease characterized by degenerative changes and thickening of the skin, joints, lungs, other internal organs, and blood vessel dysfunction.

Cudetaxestat received its first orphan drug designation in February 2021 for the potential treatment of IPF. Blade plans to initiate a Phase I clinical study to evaluate the effect of cudetaxestat on the pharmacokinetics of two approved IPF drugs (pirfenidone and nintedanib) in healthy volunteers. The study is expected to be completed in the first quarter of 2022. The findings will be used to guide the design of a planned Phase II clinical trial to evaluate the efficacy and safety of cudetaxestat in patients with IPF, which is expected to begin in the first half of 2022.

IASO Biotherapeutics, announced that the Office of Orphan Products Development (OOPD) of the U.S. Food and Drug Administration has officially issued a written reply, granting the company’s self-developed, fully human anti-CD19 and CD22 dual-target chimeric antigen receptor autologous T-cell injection (CT120) Orphan Drug Designation, (ODD), for the treatment of Acute Lymphoblastic Leukemia (ALL).

Obtaining FDA Orphan Drug Designation will accelerate the progress of CT120’s clinical trials and marketing registration in the United States. The preferential policies that CT120 will enjoy include FDA support for clinical research, waiver of certain fees, and seven-year marketing exclusivity in the United States upon FDA approval.

The orphan drug designation is based on the excellent safety and efficacy of CT120. In an investigator-initiated clinical study (registration number ChiCTR2000038641), all 4 subjects with B-cell ALL achieved complete response (CR) after receiving CT120 treatment, with a Complete Remission Rate (CRR) of 100% and no Grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) observed. Therefore, CT120 is expected to become an innovative treatment for relapsed/refractory B-ALL.

Neuroene Therapeutics announced that the FDA has granted orphan drug designation to the company’s patented compound NT102.

NT102 was developed as part of a new proprietary platform of mitochondrial and neuroprotective chemicals for the treatment of neurological diseases such as drug-resistant epilepsies.

In National Institutes of Health (NIH)-funded preclinical studies, NT102 was shown to be well tolerated and orally bioavailable, with excellent brain penetration. NT102 demonstrated broad seizure protection in several preclinical animal models, demonstrating particularly excellent seizure protection in Dravet syndrome, a rare childhood syndrome characterized by severe encephalopathy and epilepsy.

Under the Orphan Drug Act, the FDA grants orphan drug designation to drugs that treat rare diseases or conditions, typically those that affect fewer than 200,000 people in the United States.

In the Anticonvulsant Drug Development (ADD) program at the University of Utah, Neuroene’s collaborators conducted efficacy studies in the Dravet Syndrome mouse model, which had the same gene mutation as most patients with Dravet syndrome and displayed a similar phenotype to human Dravet Syndrome patients, including heat-induced seizures and spontaneous recurrent seizures. The ADD found that while only combinations of FDA-approved antiseizure drugs were effective in reducing seizures in this model, NT102 showed strong single-agent efficacy.

About Dravet Syndrome

Dravet syndrome is a rare childhood syndrome that affects 1/15,700 births in the United States and is characterized by encephalopathy and epilepsy. Because many symptoms are not apparent in a child’s first year of life, it can be difficult to diagnose.

Seizures are the most common symptom and can appear after an increase in core body temperature (e.g. fever, hot bath), with continued frequency occurring thereafter, often progressing in severity.

In 80–90% of Dravet syndrome cases, the disease is caused by a mutation in the SCN1A gene, encoding a subunit of the voltage gated sodium channel Nav1.1. Insufficient activity of this sodium channel alters excitatory/inhibitory balance in the brain, causing hyperexcitability.


1. Menarini Receives FDA Orphan Drug Designation for SEL24/MEN1703, a first in class, dual PIM/FLT3 inhibitor for the Treatment of Acute Myeloid Leukemia

2. Blade Therapeutics Announces FDA Orphan Drug Designation Granted to Cudetaxestat for Treatment of Systemic Sclerosi



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