FDA Fast Tracks SONALA-001 Plus MR-Guided Focused Ultrasound in DIPG

• Diffuse intrinsic pontine glioma (DIPG) is a rare and aggressive pediatric brain tumor that has a median survival of 7-11 months after diagnosis and currently, no effective treatment options are available beyond radiation.

• This fast track designation (FTD) allows for more frequent meetings with the FDA to discuss the development plan for the drug and discuss the appropriate data needed to support its potential approval.

• SONALA-001 previously received an orphan drug designation from the FDA in 2021 for malignant gliomas.

The FDA granted an FTD to the development program of SONALA-001 in combination with the INSIGHTEC Exablate 4000 Type-2 Device for the treatment of patients with DIPG.¹

SONALA-001 is a proprietary intravenous aminolevulinic acid HCl (ALA) formulation being developed by SonALAsense. This sonodynamic therapy utilizes the energy of ultrasound to create light in the brain, which activates protoporphyrin IX, a metabolite of ALA.

The safety and efficacy of the agent is currently under investigation in the open-label, phase 2 SDT-201 clinical trial (NCT05123534). This FTD follows an orphan drug designation that was previously granted to SONALA-001 by the FDA in 2021 for patients with malignant gliomas.

“Receiving fast track designation underscores the immediate and urgent need to bring new therapy options for DIPG patients,” said Ely Benaim, MD, chief medical officer and executive vice president of development at SonALAsense, in a press release.¹ “We are committed to working as efficiently as possible to bring SONALA-001 SDT to patients with this universally fatal disease.”

The phase 2 SDT-201 trial in DIPG is a dose-escalation study evaluating the safety, pharmacokinetics, and preliminary efficacy of ascending drug and energy dose combinations for sonodynamic therapy through the use of SONALA-001 combined with Exablate 4000 Type 2.0 MR-guided focused ultrasound.²

Enrollment in the trial is open to patients with newly diagnosed, radiographically typical DIPG with or without histologic confirmation who have had prior treatment with a minimum of 54 Gy standard focal radiotherapy administered over 42-49 days. Patients must be ≥ 4 weeks and ≤ 24 weeks post radiotherapy, have recovered from acute effects to CTCAE (version 5) grade 1 or baseline prior to day 1, have stable to improved imaging by RAPNO criteria, a Karnofsky performance scale or Lansky performance score assessed within 14 days of day 1 must of ≥ 50%, and adequate organ and marrow function.

Patients who are being treated with steroids must be on a stable to decreasing dose of steroids with the maximum dexamethasone dose of 1 mg/m²/day prior to day. The minimum age for enrollment is 5 years, but patients younger than 5 may be eligible after discussion with the sponsor medical monitor/designee. Further, patients are required to have a minimum head circumference of 52 cm as measured by physical exam, however, if the patient's head circumference is smaller than 52 cm, they also may be eligible after discussion with the sponsor medical monitor/designee.

The primary end points being evaluated are safety, tolerability, and to determine the maximum tolerated dose or recommended phase 2 dose of MR-Guided Focused Ultrasound energy in combination with SONALA-001 in this patient population. Secondary end points include objective response rate, pharmacokinetics, mechanical performance of Exablate 4000 Type 2.0 device, progression-free survival, duration of response, and overall survival.

With an estimated enrollment of 27 patients and study completion date of August 12, 2025, the study is actively recruiting patients in California and the District of Columbia.

Preliminary data from the dose ranging cohort of the study will be presented at the 2023 Society for Neuro-Oncology Annual Meeting in Vancouver, Canada, November 16-19.¹

“We are excited for the opportunity to present promising results generated from our DIPG study to date,” said Mark de Souza, chief executive officer of SonALAsense, in a press release.1 “We are fully committed in our efforts to provide hope to this group of patients of the utmost medical need, and to bring this novel treatment to patients as quickly as possible.”

REFERENCES

FDA grants fast track designation to SonALAsense’s SONALA-001 in combination with the INSIGHTEC transcranial ultrasound device for sonodynamic therapy of DIPG, a rare pediatric brain cancer. News release. SonALAsense. November 14, 2023. Accessed November 14, 2023. https://tinyurl.com/5bsmmjex

A phase 2 study of sonodynamic therapy using SONALA-001 and exablate 4000 type 2.0 in patients with DIPG. ClinicalTrials.gov. Updated October 23, 2023. Accessed November 14, 2023. https://www.clinicaltrials.gov/study/NCT05123534