Rare Daily Staff

The U.S. Food and Drug Administration granted Fast Track designation to three companies for their experimental therapies targeting rare conditions: Asklepios BioPharmaceutical’s LION-101 gene therapy for the treatment of limb-girdle muscular dystrophy; Catalyst Biosciences’ subcutaneous MarzAA for the treatment of episodic bleeding in Factor VII deficiency; and Syndax Pharmaceuticals’ SNDX-5613 for the treatment of relapsed/refractory acute leukemias.

The FDA’s Fast Track designation is designed to facilitate the development and expedite the review of new therapeutics that are intended to treat serious conditions and fill an unmet medical need, enabling new therapeutics to reach the patient earlier. Therapeutics that receive this designation receive benefits that include more frequent meetings with the FDA to discuss development and, if relevant criteria are met, eligibility for Accelerated Approval and Priority Review.

Bayer subsidiary Asklepios BioPharmaceutical’s (AskBio) LION-101 is a novel recombinant adeno-associated virus (rAAV) based vector being developed as a one-time intravenous infusion for the treatment of patients with LGMD Type 2I/R9.

LGMD comprise a group of diseases that cause progressive weakness and wasting of the muscles in the arms and legs. The muscles most affected are those closest to the body (proximal muscles), specifically the muscles of the shoulders, upper arms, pelvic area and thighs. The severity, age of onset, and features of LGMD vary among the many subtypes of the condition and are often inconsistent, even within the same family. LGMD2I/R9 is a form of LGMD and is caused by mutations in the FKRP gene. In LGMD2I/R9, signs and symptoms often develop in late childhood and may include difficulty running and walking. The symptoms gradually worsen over time towards significant disability, and affected people generally rely on a wheelchair for mobility approximately 23-26 years after onset. Currently, there is no treatment that modifies the disease progression, and treatment is based on the signs and symptoms present in each individual.

The FDA recently cleared an Investigational New Drug (IND) application for LION-101, to authorize the start of a phase 1/2 multicenter study which will evaluate the safety, tolerability, and efficacy of a single intravenous infusion of gene therapy, in adult and adolescent subjects with genotypically confirmed LGMD2I/R9. AskBio plans to initiate dosing for the LION-101 phase 1/2 clinical study in the first half of 2022.

Catalyst Biosciences’ MarzAA (marzeptacog alfa (activated) is a subcutaneously administered next-generation engineered coagulation Factor VIIa for the treatment of episodic bleeding in subjects with Factor VII deficiency. Catalyst is currently enrolling patients with FVII deficiency in a phase 1/2 open-label study, which is being conducted in parallel with the ongoing phase 3 registration trial evaluating MarzAA for the treatment of episodic bleeds in patients with hemophilia A or B with inhibitors.

FDA granted Fast Track designation for MarzAA for the subcutaneously administered treatment and control of episodic bleeding in subjects with hemophilia A or B with inhibitors in December 2020.

Syndax Pharmaceuticals’ Fast Track designation for SNDX-5613 is for the treatment of adult and pediatric patients with relapsed or refractory acute leukemias harboring a mixed lineage leukemia rearranged (MLLr) or nucleophosmin (NPM1) mutation, with currently no approved therapies. SNDX-5613 is a highly selective, oral menin inhibitor that is currently being evaluated in a phase 1/2 open-label clinical trial for the treatment of relapsed/refractory (R/R) acute leukemias.

Rearrangements of the MLL gene give rise to mixed lineage leukemia rearranged (MLLr) acute leukemias known to have a poor prognosis, with less than 25 percent of adult patients surviving past five years. MLL rearrangements produce fusion proteins that require interaction with the protein called menin to drive leukemic cancer growth. Disruption of the menin-MLLr interaction has been shown to halt the growth of MLLr leukemic cells. MLLr leukemias occur in approximately 80 percent of infant acute leukemias and up to 10 percent of all acute leukemias.

NPM1 mutant acute myeloid leukemia (AML), which is distinguished by point mutations in the NPM1 gene that drive the leukemic phenotype, is the most common type of cytogenetically normal adult AML and represents approximately 30 percent of all adult AML cases. This subtype of AML has a five-year overall survival rate of approximately 50 percent. NPM1 mutant AML is highly dependent on the expression of specific developmental genes shown to be negatively impacted by inhibitors of the menin-MLL interaction.

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