The Food and Drug Administration (FDA) has cleared Abbott’s Liberta RC deep brain stimulation (DBS) system for individuals with movement disorders.

The Liberta RC DBS system is indicated for the following:

• Bilateral stimulation of the subthalamic nucleus or the internal globus pallidus as an adjunctive therapy to reduce some of the symptoms of advanced levodopa-responsive Parkinson disease that are not adequately controlled by medications.
• Unilateral or bilateral stimulation of the ventral intermediate nucleus of the thalamus for the suppression of disabling upper extremity tremor in adult essential tremor patients whose tremor is not adequately controlled by medications and where the tremor constitutes a significant functional disability.

According to Abbott, Liberta RC DBS is the smallest rechargeable DBS device on the market with remote programming, approximately the “height and width of a smartwatch face”. Under standard settings, the system requires the fewest recharges, at 10 recharge sessions a year, for most users using a wireless charger system that is placed over the device. For users who prefer a weekly charging schedule, the system needs 30 minutes to charge.

The Liberta RC DBS system works with Abbott’s NeuroSphere Virtual Clinic, which allows individuals to communicate remotely with physicians, ensure proper settings and functionality, and receive new treatment settings. 

Users will be able to control the system via an Abbott supplied patient controller or a secure, compatible iOS device. 

HealthDay News — Xanthine dehydrogenase/oxidase blockers may reduce the risk for neurodegenerative diseases, according to a study published online May 17 in PLOS ONE.

Yizhe Song, from the Washington University School of Medicine in St. Louis, and colleagues conducted a population-based, case-control study of US Medicare beneficiaries in 2009 to identify prescription medications associated with a lower risk for 3 neurodegenerative diseases: Parkinson disease, Alzheimer disease, and amyotrophic lateral sclerosis. The analysis included 42,885 patients with neurodegenerative disease and 334,387 randomly selected controls. All filled medications were categorized according to their biological targets and mechanisms of action of those targets using medication data from 2006 to 2007. The odds ratios were estimated for 141 target-action pairs and each neurodegenerative disease. For target-action pairs inversely associated with diseases, replication was attempted in a cohort, including an active comparator group.

The researchers found that the most consistent inverse association across all 3 neurodegenerative diseases was for xanthine dehydrogenase/oxidase blockers, tied to the gout medication allopurinol. In multinomial regression, allopurinol was associated with a 13 to 34% lower risk for each neurodegenerative disease group and a mean reduction of 23% overall compared with those not using allopurinol. In the replication cohort, there was a 23% reduction for neurodegenerative diseases observed in the fifth year of follow-up comparing allopurinol users versus nonusers; with an active comparator group, more marked associations were seen.

“The medication associations we studied relate to disease risk,” a coauthor said in a statement. “Further research will be necessary to examine whether this mechanism slows progression of these diseases.”

Abstract/Full Text

ANPD001 is an autologous neuron replacement therapy that is generated using a patient’s own skin cells to manufacture dopamine neuronal precursor cells (DANPCs). The DANPCs are then transplanted into the patient through surgery. These cells then replace the ones lost or damaged by disease. 

Early data from animal models suggest that the treatment may restore dopamine signaling deficits. The efficacy and safety of ANPD001 in patients with moderate to severe Parkinson disease will be evaluated in an upcoming single-arm, open-label, phase 1/2a study. 

“We are pleased that FDA has granted Fast Track Designation, underscoring the potential of an autologous dopamine replacement therapy such as ANDP001 to serve as a meaningful treatment option,” said Damien McDevitt, PhD, Aspen president and CEO. “People with Parkinson’s disease have a significant unmet medical need and have been waiting for many years for more advanced treatment options.”

Apomorphine, a non-ergoline dopamine agonist, is believed to treat off episodes associated with Parkinson disease through stimulation of postsynaptic dopamine D2-type receptors within the caudate-putamen in the brain. SPN-830 provides a continuous subcutaneous infusion of apomorphine through an infusion pump. 

Supernus had originally submitted the NDA for SPN-830 back in September 2020. The application included data from the phase 3 TOLEDO study (ClinicalTrials.gov Identifier: NCT02006121) and a supportive open-label study (ClinicalTrials.gov Identifier: NCT02339064). Results from the TOLEDO study showed that SPN-830 was associated with a statistically significant reduction in mean daily off time compared with placebo.

The FDA subsequently issued a Refusal to File (RTF) letter stating that the NDA was not sufficiently complete to permit a substantive review. In December 2021, the Company resubmitted the NDA after the Agency provided additional guidance related to the requested documents and reports cited in the RTF letter. 

In October 2022, the Agency issued a Complete Response Letter (CRL) to Supernus requesting additional information and analysis related to the infusion device and the drug product across several areas of the NDA. The application was resubmitted in October 2023 with the requested information. A regulatory decision is expected on April 5, 2024.

“We are pleased with the FDA’s acceptance of our NDA resubmission for SPN-830 and look forward to continuing to work with them during their review,” said Jack Khattar, President and CEO of Supernus. “SPN-830 is an important product candidate which, if approved by the FDA, represents a novel and less invasive treatment option for PD patients.”

This is the second CRL the Company has received for SPN-830. The drug/device combination therapy provides a continuous subcutaneous infusion of apomorphine through an infusion pump. Efficacy was established based on data from the phase 3 TOLEDO study (ClinicalTrials.gov Identifier: NCT02006121) and a supportive open-label study (ClinicalTrials.gov Identifier: NCT02339064).

In the letter, the FDA cited that additional information on product quality and the infusion device was still needed before the Agency could make a decision on approval. No clinical or safety issues were noted in the CRL.

“We remain committed to bringing SPN-830 to the market as an important treatment option for PD patients who experience motor fluctuations associated with off episodes,” said Jack Khattar, President & CEO of Supernus. “We will work with the FDA to address the CRL and to successfully resubmit our SPN-830 NDA.” 

Apomorphine, a non-ergoline dopamine agonist, is believed to treat off episodes associated with Parkinson disease through stimulation of postsynaptic dopamine D₂-type receptors within the caudate-putamen in the brain.

Ceftobiprole for the Treatment of Serious Bacterial Infections

PDUFA date: April 3, 2024

Ceftobiprole is a broad spectrum cephalosporin antibiotic for intravenous administration. The drug has been shown to have rapid bactericidal activity against Gram positive bacteria such as Staphylococcus aureus, including methicillin-resistant strains (MRSA), and Gram negative bacteria. Basilea is seeking approval for 3 indications: S. aureus bacteremia (SAB), including right-sided infective endocarditis, acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The application is supported by data from three phase 3 studies: ERADICATE (ClinicalTrials.gov Identifier: NCT03138733), TARGET (ClinicalTrials.gov Identifier: NCT03137173), and a phase 3 study in CABP (ClinicalTrials.gov Identifier: NCT00326287). Findings from these trials supported the effectiveness of ceftobiprole in the treatment of SAB, ABSSSI, and CABP vs a comparator antibiotic.

SPN-830 for Continuous Treatment of Motor Fluctuations in Parkinson Disease

PDUFA date: April 5, 2024

SPN-830 is an apomorphine infusion device that provides continuous treatment of motor fluctuations (off episodes) in adults with Parkinson disease. The drug/device combo had originally been submitted to the FDA for review in September 2020. The application included data from the phase 3 TOLEDO study (ClinicalTrials.gov Identifier: NCT02006121) and a supportive open-label study (ClinicalTrials.gov Identifier: NCT02339064). Results from TOLEDO showed that SPN-830 was associated with a statistically significant reduction in mean daily off time compared with placebo. The FDA subsequently issued a Refuse to File letter, and then a Complete Response Letter, which required Supernus to provide additional analysis for review. Apomorphine, a non-ergoline dopamine agonist, is currently available as a solution for subcutaneous injection and as a sublingual film.

N-803 plus BCG for High-Risk Non-Muscle-Invasive Bladder Cancer

PDUFA date: April 23, 2024

N-803 (Anktiva^®) is an interleukin-15 (IL-15) superagonist complex consisting of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. The investigational agent is being reviewed in combination with Bacillus Calmette-Guérin (BCG) for the treatment of BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) carcinoma in situ (CIS) with or without Ta or T1 disease. The BLA is supported by data from the phase 2/3, open-label QUILT-3.032 study (ClinicalTrials.gov Identifier: NCT03022825). Findings showed 71% of patients with BCG-unresponsive NMIBC CIS and papillary disease treated with intravesical BCG plus N-803 achieved a complete response (primary endpoint), with median duration of response of 26.6 months. Among patients with CR, the Kaplan-Meier-estimated probability of avoiding cystectomy and of bladder cancer-specific survival was 89.2% and 100%, respectively, at 24 months. 

Tovorafenib for Relapsed or Progressive Pediatric Low-Grade Glioma

PDUFA date: April 30, 2024

Tovorafenib is an oral, brain-penetrant, highly-selective type II RAF kinase inhibitor designed to target a key enzyme in the MAPK signaling pathway. It is being reviewed for the treatment of relapsed or progressive pediatric low-grade glioma (pLGG). The NDA includes efficacy and safety data from the open-label, phase 2 FIREFLY-1 study (ClinicalTrials.gov Identifier: NCT04775485), which included 77 patients 6 months to 25 years of age with relapsed or progressive pLGG. Findings showed that among the 69 evaluable patients, the overall response rate (by Response Assessment for Neuro-Oncology High Grade Glioma criteria) was 67%, with median duration of response of 16.6 months. Tovorafenib was granted Rare Pediatric Disease Designation for relapsed or progressive pLGG.

Mavorixafor for the Treatment of WHIM Syndrome

PDUFA date: April 30, 2024

Mavorixafor is an investigational oral small-molecule antagonist of the CXCR4 receptor. It is being reviewed for the treatment of patients 12 years of age and older with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, a rare, primary immunodeficiency. The application includes data from the phase 3, double-blind, placebo-controlled 4WHIM study (ClinicalTrials.gov Identifier: NCT03995108), which evaluated oral, once-daily mavorixafor vs placebo in patients with genetically confirmed WHIM syndrome (N=31). Findings showed mavorixafor was associated with statistically significant and clinically relevant longer times above threshold levels for both absolute neutrophil (P <.0001) and absolute lymphocyte counts (P <.0001) compared with placebo. Treatment with mavorixafor also resulted in reductions in the rate, severity, and duration of infections vs placebo.

The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to Amneal Pharmaceuticals regarding the New Drug Application (NDA) for IPX203 for the treatment of Parkinson disease.

IPX203 is a novel, oral capsule formulation that contains immediate-release (IR) granules of carbidopa and levodopa and extended-release beads of levodopa. The application included data from the phase 3 RISE-PD trial (ClinicalTrials.gov Identifier: NCT03670953), which compared the efficacy and safety of IPX203 to carbidopa/levodopa (CD/LD) IR in Parkinson disease patients with motor fluctuations. Treatment with IPX203 was associated with a statistically significant improvement in “Good On” time and with significantly less “Off” time compared with CD/LD IR.

According to the letter, the product could not be approved based on the data provided as additional information was needed on the safety of the carbidopa component. The pharmacokinetic studies had only established the safety of one ingredient, levodopa.

“We are committed to advancing IPX203 for Parkinson disease, which has been developed to provide a longer duration of therapeutic benefit than existing formulations with fewer doses,” said Chirag and Chintu Patel, Co-Chief Executive Officers at Amneal. “We plan to work closely with the FDA to address the agency’s feedback and we remain confident in bringing this new treatment to Parkinson patients as soon as possible.”

The Agency did not identify any issues related to clinical efficacy or manufacturing.

The Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to AbbVie regarding the New Drug Application (NDA) for ABBV-951 (foscarbidopa/foslevodopa) for the treatment of motor fluctuations in adults with advanced Parkinson disease.

ABBV-951 is a solution of levodopa and carbidopa prodrugs for continuous subcutaneous (SC) delivery. The NDA submission was supported by data from the M15-736 study (ClinicalTrials.gov Identifier: NCT04380142), which compared ABBV-951 administered via continuous SC infusion for 24 hours/day to oral immediate-release levodopa/carbidopa in 130 patients aged 30 years and older with advanced Parkinson disease. Findings showed that treatment with ABBV-951 was associated with statistically superior reductions in motor fluctuations compared with oral levodopa/carbidopa.

In the CRL, the FDA requested that additional information about the infusion pump be provided as part of the NDA review. AbbVie plans to resubmit the application quickly as no additional efficacy or safety trials related to the drug were required.

“There is an unmet need for people living with advanced Parkinson disease as they face daily challenges in managing their condition,” said Thomas Hudson, MD, senior vice president, research and development, chief scientific officer, AbbVie. “We will continue to work closely with the FDA as part of our commitment to bringing this treatment option to people impacted by this disease as quickly as possible.”

The table below is a review of notable updates that occurred in July 2023 for investigational products in development (not an inclusive list). Click on the status to view our full coverage.