FDA Grants Fast Track Status to KYV-101 for Refractory Lupus Nephritis Treatment

Kyverna Therapeutics announced that the FDA has given Fast Track status to KYV-101, a treatment for patients suffering from resistant lupus nephritis (LN). KYV-101 is an innovative therapy that uses anti-CD19 chimeric antigen receptor T-cells (CAR T) to eliminate B cells, including those that are self-reactive, in individuals with autoimmune diseases.

Peter Maag, Ph.D., CEO of Kyverna, expressed his enthusiasm about the FDA granting Fast Track designation for KYV-101. This designation enables the company to expedite the process of making this potentially groundbreaking and life-saving medication available to individuals with lupus nephritis.

It is believed that KYV-101 has the potential to significantly and swiftly decrease disease activity in Lupus Nephritis patients. The anticipation is to disclose clinical data regarding patients in the latter half of 2023.

Kyverna is currently enrolling patients in multiple locations throughout the United States for their Phase 1 clinical trial of KYV-101. This trial is open-label and being conducted at various centers. Additionally, Kyverna has submitted its initial Clinical Trial Application (CTA) to the Paul Ehrlich Institute (PEI) in Germany, seeking approval for a parallel Phase 1/2 clinical trial of KYV-101 in LN within the European Union (EU).

Fast Track designation is a special status given to new treatments aimed at treating severe or life-threatening conditions that have the potential to fulfill unmet medical needs. Its purpose is to streamline the development and review process, allowing these drugs to reach patients in a timelier manner. Therapies granted Fast Track designation benefit from increased communication and collaboration with the FDA, and under certain circumstances, they may be eligible for Accelerated Approval and Priority Review, expediting their path to market if they meet the necessary criteria.

Annovis Bio Announces Completion of Phase III Parkinson’s Disease Treatment Enrollment at Record Pace

Annovis Bio has declared that its phase III study for buntanetap, the company’s primary compound for Parkinson’s disease, has successfully enrolled the required number of participants within an exceptional nine-month timeframe. Since the study commenced in late August 2022, more than 640 patients underwent screening, and an impressive total of 520 patients were enrolled at an accelerated pace. This achievement was made possible through the collaboration of 67 sites, with 43 located in the United States and 24 in the European Union.

The phase III trial is a controlled study that employs randomization, double-blinding, and a placebo control to investigate the effectiveness, safety, and tolerability of buntanetap in early-stage Parkinson’s disease patients who are already receiving standard care. Buntanetap, previously known as Posiphen or ANVS401, combats neurodegeneration by reducing the levels of multiple neurotoxic proteins. This mechanism enhances synaptic transmission and axonal transport, which are vital for the efficient flow of information within nerve cells. The degeneration and eventual demise of nerve cells are attributed to disruptions in these processes. Notably, buntanetap differs from other drugs under development for Parkinson’s disease as it inhibits the formation of multiple toxic proteins rather than targeting just one. By doing so, it prevents the buildup of major neurotoxic proteins that are associated with both Parkinson’s disease and Alzheimer’s disease.

Buntanetap enhances axonal transport, reduces inflammation, promotes nerve cell health, and ameliorates motor and cognitive dysfunction by decreasing the levels of neurotoxic proteins.

The exceptional enrollment numbers and minimal dropout rate are attributed to various factors. The drug demonstrated improvements in body and motor function during the phase I/II trials, it necessitates only a once-daily pill, and it has been proven to be safe and well-tolerated. The study is anticipated to conclude in November, and the top-line assessment data is expected to be available by the end of the year.

According to Dr. Maria Maccecchini, founder, president, and CEO of Annovis, the Parkinson’s community is highly knowledgeable and connected. When they became aware of Annovis’ innovative and patient-centered approach, which demonstrated early therapeutic potential, they expressed a strong desire to contribute and make a significant impact. Dr. Maria believes that the implications of such a drug therapy could be revolutionary not only for Parkinson’s disease but for all neurodegenerative diseases.

Gilteritinib as Maintenance Therapy Demonstrated Benefit in Subgroups of FLT3-ITD Acute Myeloid Leukemia Patients

On June 9, 2023, Astellas Pharma Inc. (TSE: 4503) and the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) presented data from the Phase 3 MORPHO clinical trial which demonstrated favorable results in subgroups of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutated acute myeloid leukemia (AML) patients, including a subgroup of patients with detectable measurable residual disease (MRD). The data was presented at the 2023 European Haematology Association (EHA) Hybrid Congress in Frankfurt, Germany and was discussed in an oral session on June 11. 

Gilteritinib is an FMS-like tyrosine kinase 3 (FLT3) inhibitor, and it has been shown to be active against FLT3-ITD mutations, a common driver mutation that is associated with a high disease burden and a poor prognosis. Astellas has exclusive global development, commercialization, and manufacturing rights to gilteritinib. It was found in a research partnership with Kotobuki Pharmaceutical. For treating adult patients with R/R FLT3+ Acute Myeloid Leukemia, gilteritinib is available under the brand name XOSPATA® in the United States, Japan, China, and a few European nations.

These data from the Phase 3 MORPHO trial, which evaluated gilteritinib as a maintenance therapy following allogeneic hematopoietic stem cell transplantation (HSCT) for patients with FLT3-ITD AML, did not demonstrate statistically significant improvement of relapse-free survival (RFS) in the entire cohort (Hazard Ratio [HR] for gilteritinib versus placebo 0.68; P=0.0518). However, there was a clinical improvement of RFS in a subgroup of patients with detectable MRD at 2 years with HR: 0.515; 95% Confidence Interval [CI], 0.316-0.838; nominal P=0.0065) compared to patients without detectable MRD (HR: 1.213; 95% CI, 0.616-2.387; nominal P=0.575).

“While we are continuing to conduct a thorough assessment of the full data set from our Phase 3 MORPHO trial, we are encouraged by these data, which explore the potential of gilteritinib in a maintenance setting. Acute Myeloid Leukemia patients with a FLT3-ITD mutation often face worse outcomes than those with other mutations and have restricted post-HSCT treatment options with unmet need. With these findings, we remain focused on sharing updates with the scientific community to inform continued innovation for the AML community.” – Ahsan Arozullah, M.D., M.P.H., Senior Vice President and Head of Oncology Development, Astellas. 

As the Acute Myeloid Leukemia treatment landscape continues to evolve, the exploration of prognostic indicators like MRD, which may be used to guide the management of Acute Myeloid Leukemia, is vital to advance science and patient care. We look forward to continuing our collaboration with Astellas to explore innovative approaches for those impacted by Acute Myeloid Leukemia. – said Mary M. Horowitz, M.D., Principal Investigator of the BMT CTN Data and Coordinating Center.

The Phase 3 MORPHO trial is a randomized, double-blind, placebo-controlled, multicenter trial that compares gilteritinib to placebo as maintenance therapy over a period of two years following HSCT in 356 patients with FLT3-ITD mutated Acute Myeloid Leukemia and in remission after induction therapy. The study did not meet its pre-defined primary endpoint of RFS and key secondary endpoint of overall survival or patients treated with gilteritinib compared to placebo. In FLT3-ITD Acute Myeloid Leukemia patients, TEAEs associated with gilteritinib compared to placebo were neutrophil decrease (42.1% versus 15.8%) and increased incidence of chronic graft-versus-host disease (GVHD) (52.2% versus 42.1%). Additional data and sub-analyses will be submitted for publication and for consideration at upcoming medical meetings.

DTx Pharma Receives FDA Orphan Drug Designation for DTx-1252 for the Treatment of Charcot-Marie-Tooth Disease Type 1A (CMT1A)

On June 7, 2023, DTx Pharma announced that the US FDA had granted Orphan Drug Designation to DTx-1252, an investigational FALCON small interfering RNA (siRNA) therapeutic for the treatment of Charcot-Marie-Tooth Disease Type 1A (CMT1A). CMT1A is a progressive, neuromuscular, autosomal-dominant disease that leads to life-long loss of muscle function and disability.

We are pleased to receive Orphan Drug Designation from the FDA for DTx-1252. Patients living with Charcot-Marie-Tooth Disease Type 1A are in urgent need of treatment, and this represents a significant step forward for the patients and the DTx team as we advance DTx-1252 toward the clinic. DTx-1252 targets the underlying genetic lesion of the disease and leverages our FALCON platform to unlock the promise of RNAi therapeutics. We look forward to the continued development of DTx-1252. – Artie Suckow, Ph.D., co-founder and CEO of DTx Pharma.

DTx-1252, is a novel, potential first-in-class FALCON™ siRNA drug candidate targeting PMP22. The asset boasts a robust preclinical package, demonstrating the reversal of disease in preclinical rodent models and translation to higher species, with IND-enabling studies near completion. By repressing PMP22, DTx-1252 reverses CMT1A in a mouse model that faithfully recapitulates the genetic and clinical manifestations of the disease. DTx-1252 treatment induces remyelination of axons to normal levels, improves relevant electrophysiological measurements, and increases muscle mass, grip strength, coordination, and agility in preclinical studies.

The most prevalent inherited neuromuscular disorder, CMT1A, affects 150,000 people in the U.S. and EU. There are no approved treatments for Charcot-Marie-Tooth Disease Type 1A. The overexpression of the PMP22 gene in Schwann cells, which is the cause of Charcot-Marie-Tooth Disease Type 1A, prevents the myelination of peripheral nerves and results in progressive muscle atrophy, neuropathic pain, difficulty walking, and, for many, the inability to live independently, and is having a significant and debilitating impact on patient lives.

FibroGen Announces Topline Results from LELANTOS-1 Phase 3 Clinical Study of Pamrevlumab in Non-Ambulatory Patients with Duchenne Muscular Dystrophy

On June 07, 2023, FibroGen, Inc. (NASDAQ: FGEN) announced topline data from the Phase 3 LELANTOS-1 placebo-controlled trial of pamrevlumab for the treatment of non-ambulatory patients with Duchenne Muscular Dystrophy (DMD) on background corticosteroids. The Performance of the Upper Limb 2.0 (PUL 2.0) score at week 52 as compared to baseline was not met by the study’s primary aim. The majority of adverse events that developed during therapy were mild or moderate, and pamrevlumab was usually well tolerated and safe.

The complete results of the LELANTOS-1 study will be presented by FibroGen at an upcoming medical conference and along with full data. Topline results from the pamrevlumab Phase 3 LELANTOS-2 clinical study for the treatment of ambulatory Duchenne Muscular Dystrophy patients are anticipated in the third quarter of 2023.

While disappointed with these results, we look forward to sharing the data at a future medical conference to contribute towards the understanding of this devastating disease. FibroGen would like to thank the patients, caregivers and clinical trial investigators for their dedication in participating in this study. –  said Enrique Conterno, Chief Executive Officer, FibroGen.

A total of ninety-nine (99) Duchenne Muscular Dystrophy patients aged 12 years and older were enrolled in LELANTOS-1, a global Phase 3, randomized, double-blind, trial of pamrevlumab or placebo in combination with systemic corticosteroids to evaluate the efficacy and safety of pamrevlumab in patients with non-ambulatory DMD. Pamrevlumab is a potential first-in-class antibody being developed by FibroGen to inhibit the activity of connective tissue growth factor (CTGF), a common factor in fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. 

The Phase 3 clinical development program for pamrevlumab for DMD includes two studies, LELANTOS-1 and LELANTOS-2. These randomized, double-blind global Phase 3 trials are designed to evaluate the efficacy and safety of pamrevlumab in combination with systemic corticosteroids in patients with either non-ambulatory or ambulatory DMD. In order to assess the effectiveness and safety of pamrevlumab in patients with non-ambulatory DMD, a total of 99 DMD patients aged 12 and older were enrolled in LELANTOS-1. Earlier, the US FDA has granted Rare Pediatric Disease, Orphan Drug, and Fast Track Designation to pamrevlumab for the treatment of Duchenne Muscular Dystrophy. In the EU, FibroGen has been granted Orphan Drug Designation to pamrevlumab for the treatment of DMD. Moreover, the U.S. Food and Drug Administration has also granted Rare Pediatric Disease Designation to pamrevlumab for the treatment of patients with Duchenne Muscular Dystrophy. 
Duchenne muscular dystrophy (DMD) is a rare and debilitating neuromuscular disease that affects approximately 1 in every 5,000 newborn boys. About 20,000 children are diagnosed with Duchenne Muscular Dystrophy globally each year. The prevalence is estimated to be 1/3,500 live male births, and the age of onset is usually between 3–5 years. The fatal disease is caused by a genetic mutation leading to the absence or defect of dystrophin, a protein necessary for normal muscle function. 

Although there is no cure for any form of muscular dystrophy, treatment for some forms of the disease, including DMD can help extend the time a person with the disease can remain mobile and help with heart and lung muscle strength. The current US market possesses approved products for the treatment of patients with Duchenne Muscular Dystrophy. In the EU-4 and the UK, the current market is dominated by steroid therapies along with an approved medication targeting Duchenne Muscular Dystrophy patients with the nonsense mutation, Translarna (ataluren). Similarly, several other major pharma and biotech companies are also actively exploring Duchenne muscular dystrophy therapeutics options.