Alcyone Therapeutics Announces Continued Enrollment Approval from FDA of the PIERRE Pivotal IDE Clinical Study of the ThecaFlex DRx™ System for Administration of nusinersen

Rhea-AI Summary

Alcyone Therapeutics has received FDA approval to continue enrollment in the PIERRE pivotal IDE clinical study for the ThecaFlex DRx™ System. This implantable device is being investigated for routine subcutaneous administration of nusinersen to treat spinal muscular atrophy (SMA). The first stage, involving 10 SMA patients, has been completed with no device-related adverse events. The FDA has approved enrollment of an additional 80 SMA patients across 30 centers in the U.S. and Europe.

Key observations include:

• Implantation duration: 1-2 hours
• Hospital discharge: Within 24 hours
• Infusion procedure: Less than 30 minutes
• Actual nusinersen infusion: Less than 10 minutes

The ThecaFlex system aims to provide a less invasive, more accessible alternative to repeat lumbar puncture for SMA patients receiving SPINRAZA® (nusinersen) therapy.

Positive

• FDA approval to continue enrollment in the PIERRE pivotal IDE clinical study
• No device-related adverse events observed in the first 10 SMA patients
• Successful aspiration and infusion through the ThecaFlex port in all attempts
• Potential for less invasive and more accessible treatment for SMA patients
• Possible reduction in anesthesia and radiation exposure compared to repeat lumbar puncture

Negative

• None.

Medical Research Analyst

The FDA's approval for continued enrollment in the PIERRE study marks a significant milestone for Alcyone Therapeutics' ThecaFlex DRx™ System. This decision, based on promising initial results, could potentially revolutionize the administration of nusinersen for SMA patients.

Key points to consider:

• The successful completion of the first stage with 10 SMA patients without device-related adverse events is encouraging.
• The expansion to 80 additional patients across 30 centers will provide a more robust dataset to evaluate the system's safety and efficacy.
• The observed implantation time of 1-2 hours and discharge within 24 hours suggest a relatively straightforward procedure.
• The infusion time of less than 10 minutes in a non-specialized setting could significantly improve patient experience and resource utilization.

If successful, the ThecaFlex system could address major challenges in nusinersen administration, potentially improving treatment adherence and outcomes for SMA patients. However, long-term safety and efficacy data will be important for FDA approval and widespread adoption.

Biotech Industry Analyst

Alcyone Therapeutics' progress with the ThecaFlex DRx™ System has significant implications for both the company and the broader biotech landscape:

• The collaboration with Biogen (NASDAQ: BIIB) adds credibility and resources to the project, potentially accelerating development and commercialization.
• If approved, ThecaFlex could become a platform technology, extending beyond SMA to other neurological disorders requiring intrathecal drug delivery.
• The system's potential to reduce the need for anesthesia and radiation exposure could lead to cost savings for healthcare systems and improved safety for patients.
• Market opportunity could be substantial, considering the $2.6 billion in 2022 sales for Spinraza and the potential for use with other ASO therapies.

Investors should monitor the progress of the PIERRE study closely, as positive results could significantly impact Alcyone's valuation and partnership opportunities. However, it's important to note that regulatory hurdles and competition from alternative delivery methods could pose challenges.

Healthcare Technology Expert

The ThecaFlex DRx™ System represents a notable advancement in medical device technology for CNS drug delivery:

• The system's ability to enable subcutaneous access for intrathecal drug administration is a significant innovation in the field.
• The potential shift from specialized hospital visits to exam room settings for drug administration could greatly improve healthcare resource allocation.
• The system's design for chronic bolus intrathecal administration without indication restrictions could open up new treatment possibilities for various neurological disorders.
• The less than 30-minute infusion procedure observed in the study suggests improved efficiency compared to traditional methods.

While the initial results are promising, it's important to consider potential challenges such as long-term device durability, infection risks and the learning curve for healthcare providers. The success of ThecaFlex could catalyze further innovations in drug delivery systems for neurological conditions, potentially reshaping treatment paradigms in this field.

• Alcyone's ThecaFlex is an implantable medical device under investigation for routine subcutaneous administration of therapeutics to the cerebrospinal fluid (CSF).
• The first stage of the pivotal IDE PIERRE trial has been completed.
• 10 spinal muscular atrophy (SMA) patients have undergone ThecaFlex implantation and have received nusinersen through the device.
• No device-related adverse events, including infections, were observed in the 30 days after implantation.
• FDA has agreed to an additional 80-SMA patient, 30-center, enrollment after review of the clinical data by Data Monitoring Safety Committee of first 10 SMA patients implanted.

LOWELL, Mass., July 31, 2024 /PRNewswire/ -- Alcyone Therapeutics Inc. (Alcyone), a clinical-stage biotechnology company pioneering next-generation precision genetic therapies and precision delivery solutions of therapies for complex neurological conditions, announced today that the U.S. Food and Drug Administration (FDA) has provided approval to continue enrollment of the PIERRE study (https://clinicaltrials.gov/ct2/show/NCT05866419) to evaluate the safety and effectiveness of the ThecaFlex DRx™ subcutaneous port and intrathecal catheter system for chronic intrathecal access, CSF aspiration, and delivery of SPINRAZA^® (nusinersen) in SMA patients as an alternative to repeat lumbar puncture (LP).

As previously announced, the PIERRE IDE trial was designed to enroll up to 90 SMA patients with a minimum age of 3 years old and be conducted in two stages. The first stage, consisting of 10 SMA patients enrolled, implanted, infused with nusinersen and followed for 30 days, is complete. During the first stage of the trial, all attempts to aspirate and infuse through the ThecaFlex port were successful, and no infection or device-related adverse events were observed. Based on a review of the data from the first stage, the FDA provided approval to continue enrollment of an additional 80 SMA patients in up to 30 centers across the U.S. and Europe.

Based on experience among the first 10 SMA patients enrolled in the trial, the observed duration for implantation of ThecaFlex was between one and two hours, depending on spinal complexity of the patient, with most SMA patients discharged from the hospital within 24 hours of implantation. Following implantation, the infusion procedure was typically performed in a non-specialized setting (i.e., a standard exam room) with an observed infusion procedure duration of less than 30 minutes with the actual nusinersen subcutaneous infusion time taking less than 10 minutes.  

"As we approach the next stage of the PIERRE IDE study, we will continue to evaluate the safety and efficacy of the ThecaFlex system to help patients with spinal muscular atrophy receive the SPINRAZA^® (nusinersen) therapy," says Dr. Scellig Stone, M.D., Ph.D., FRCSC the Boston Children's Hospital primary investigator for the PIERRE study. "The initial data and patient feedback are optimistic and a key first step toward developing a less invasive, more accessible procedure that may improve the overall dosing experience for SMA patients and may help optimize hospital resources." 

"We were pleased to receive the recommendation from the independent data monitoring safety committee to continue enrollment without any changes to the PIERRE study protocol as well as the FDA's subsequent approval to continue enrollment," said Dr. Kathrin Meyer, Ph.D., Alcyone's Chief Scientific Officer and Head of Research & Development. "This represents a tangible step toward our goal of substantially improving treatment experience for patients requiring repeat intrathecal delivery of medications for the treatment of neurological disorders."

Potential clinical benefits of the ThecaFlex DRx System are currently being evaluated in the PIERRE study and may include: (a) enabling routine subcutaneous administration of ASO (antisense oligonucleotide) therapies to the cerebrospinal fluid, and (b) reducing the need for anesthesia and radiation exposure compared to repeat LP for SPINRAZA infusion in SMA subjects.

"For those who currently require anesthesia and radiographic guidance for delivery of nusinersen, which exposes them to radiation, ThecaFlex could shift administration from a specialized visit to an exam room setting," said Dr. Michael Muhonen, M.D. at the Children's Hospital of Orange County in California. "I look forward to the continued enrollment of the study and future learnings from the patient therapy administration experience with this innovative device."

Beyond this trial, if ThecaFlex is approved for chronic bolus intrathecal administration of drugs without indication restrictions, it may increase accessibility for people suffering from other neurological disorders that need repeat intrathecal drug delivery. It has the potential to be the first implantable device designed to enable routine subcutaneous access for the delivery of ASO therapies.

The PIERRE pivotal IDE trial is part of a collaboration between Biogen Inc. (Nasdaq: BIIB) and Alcyone previously announced in January 2023. Additional details can be found at https://clinicaltrials.gov/ct2/show/NCT05866419.

About The ThecaFlex DRx™ System
The ThecaFlex DRx System (ThecaFlex), a technology within Alcyone's Falcon™ Delivery Platform, is an implantable intrathecal (IT) catheter, catheter fixation device, and subcutaneous port system designed to provide access to the cerebrospinal fluid (CSF) for the infusion of therapies by IT bolus administration. Lumbar puncture (LP), commonly known as a spinal tap, is the current standard of care approach to delivering therapeutics into the CSF. ThecaFlex is designed to be an alternative to LP, especially for people with a challenging spinal anatomy or those requiring multiple anesthesia and radiation exposures for repeat LPs, or for patients for whom the treating physician determines implantation of ThecaFlex is otherwise in the patient's best interests. ThecaFlex has received a CE Mark in Europe and IDE (Investigational Device Exemption) from FDA to conduct a clinical investigation but has not yet been approved for commercial use by FDA. In addition, ThecaFlex has received Breakthrough Device Designation from FDA. For more information, visit www.alcyonetx.com.

About Alcyone Therapeutics
Alcyone Therapeutics is a clinical-stage biotechnology company pioneering next-generation precision gene-based therapies for complex neurological conditions. The company integrates innovation in neuroscience, precision dosing platforms, and manufacturing capabilities to deliver transformative therapies to patients. Alcyone leverages the synergy between Falcon™, the Company's proprietary intrathecal precision dosing and biodistribution platform that incorporates deep knowledge of cerebrospinal fluid (CSF) dynamics, computational modeling, bioengineering, and novel gene-based therapeutics platforms developed at the Abigail Wexner Research Institute (AWRI) at Nationwide Children's Hospital. This comprehensive approach allows for the optimization of central nervous system (CNS) dosing and delivery to better target the pathophysiology and anatomy specific to various neurological diseases. Alcyone's lead programs utilize X chromosome reactivation for X-linked disorders and targets the treatment of Rett syndrome. For more information, visit www.alcyonetx.com. 

About SPINRAZA^® (nusinersen)
SPINRAZA is approved to treat infants, children, and adults with spinal muscular atrophy (SMA) and is approved in more than 60 countries. As a foundation of care in SMA, more than 13,000 individuals have been treated with SPINRAZA worldwide.¹ 

SPINRAZA is an antisense oligonucleotide (ASO) that targets an underlying cause of motor neuron loss in SMA by continuously increasing the amount of full-length survival motor neuron (SMN) protein produced in the body.² It is administered directly into the central nervous system, where motor neurons reside, to deliver treatment where the disease starts.² 

SPINRAZA has demonstrated sustained efficacy across ages and SMA types with a well-established safety profile based on data in patients treated for up to eight years, combined with unsurpassed real-world experience.³ The nusinersen clinical development program encompasses more than 10 clinical studies, which have included more than 460 individuals across a broad spectrum of patient populations, including two randomized controlled studies (ENDEAR and CHERISH).  SHINE and ongoing NURTURE open-label extension studies are evaluating the long-term impact of SPINRAZA. The most common adverse events observed in clinical studies were respiratory infection, fever, constipation, headache, vomiting and back pain. Laboratory tests can monitor for renal toxicity and coagulation abnormalities, including acute severe low platelet counts, which have been observed after administration of some ASOs. 

Biogen licensed the global rights to develop, manufacture and commercialize SPINRAZA from Ionis Pharmaceuticals, Inc. (Nasdaq: IONS). Please click here for Important Safety Information and full Prescribing Information for SPINRAZA in the U.S., or visit your respective country's product website. 

References:

1. Based on commercial patients, early access patients, and clinical trial participants through March 31, 2022.
2. SPINRAZA U.S. Prescribing Information available at: https://www.spinraza.com/content/dam/commercial/specialty/spinraza/caregiver/en_us/pdf/spinraza-prescribing-information.pdf. Accessed: October 2022.
3. Core Data sheet, Version 13, October 2021. SPINRAZA. Biogen Inc, Cambridge, MA.

MEDIA & INVESTOR CONTACT:   Alcyone Therapeutics Chris Coletta + 1 978-709-1946 ir@alcyonetx.com

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SOURCE Alcyone Therapeutics

FAQ

What is the purpose of the PIERRE clinical study for the ThecaFlex DRx™ System (BIIB)?

The PIERRE study evaluates the safety and effectiveness of the ThecaFlex DRx™ System for chronic intrathecal access, CSF aspiration, and delivery of SPINRAZA® (nusinersen) in SMA patients as an alternative to repeat lumbar puncture.

How many patients are expected to be enrolled in the PIERRE study for ThecaFlex (BIIB)?

The PIERRE study is designed to enroll up to 90 SMA patients, with 10 patients in the first stage and an additional 80 patients approved for the second stage.

What were the results of the first stage of the PIERRE study for ThecaFlex (BIIB)?

In the first stage with 10 SMA patients, all attempts to aspirate and infuse through the ThecaFlex port were successful, and no infection or device-related adverse events were observed within 30 days of implantation.

How long does the ThecaFlex implantation procedure take for SMA patients (BIIB)?

The observed duration for ThecaFlex implantation was between one and two hours, depending on the spinal complexity of the patient.

What are the potential benefits of the ThecaFlex DRx System for SMA patients (BIIB)?

Potential benefits include enabling routine subcutaneous administration of ASO therapies to the cerebrospinal fluid and reducing the need for anesthesia and radiation exposure compared to repeat lumbar puncture for SPINRAZA infusion.