FDA Grants Orphan Drug Designation to Padeliporfin VTP for Pancreatic Cancer

FDA

The FDA has granted orphan drug designation to padeliporfin vascular targeted photodynamic therapy (VTP) for use as a potential therapeutic option in patients with locally advanced pancreatic cancer, according to an announcement from ImPact Biotech, the drug developer.¹

The product is comprised of the photosensitizer padeliporfin that is given intravenously via a laser light delivery system. The laser emits near-infrared (NAR) light at 752 nm and an optic fiber distributes the light to the target lesions.2 When activated by the light, the drug quickly constricts blood supply in the targeted illuminated area and leads to tumor necrosis that stimulates antitumor immunity; this results in strengthened cancer cell killing.¹

The Israeli biotech organization shared plans to submit an investigational new drug application for the product later this year, which would allow for the launch of a phase 1 trial evaluating padeliporfin VTP in patients with locally advanced pancreatic ductal adenocarcinoma. The trial is anticipated to enroll patients this year.

“We are delighted to receive orphan drug designation for padeliporfin VTP in pancreatic cancer, further validating ImPact’s technology and the potential benefits our product could bring to patients with locally advanced pancreatic cancer,” Barak Palatchi, chief executive officer of ImPact Biotech, stated in a press release. “We continue to believe and follow our strategy, refocusing padeliporfin VTP treatment on patients with limited treatment options. In pancreatic cancer, with limited treatment options for patients who have unresectable locally advanced disease our hope is that padeliporfin VTP will offer a safe and effective treatment that will render the disease eligible for definitive treatment.”

Previously, padeliporfin VTP received orphan drug designation and fast track designation³ for use in adult patients with low-grade upper-tract urothelial cancer (UTUC). Data from the phase 1 trial (NCT03617003) were presented during the 2023 ASCO Annual Meeting.²

The early-phase trial enrolled patients with residual or recurrent UTUC that was high or low grade. These patients had prior endoscopic treatment fail and were unable or unwilling to undergo surgery. The primary end point was to identify the maximum tolerated dose of laser light fluence; this was established to be 150 mW/cm for the ureter and 200 mW/cm for the kidney.

With 6 months of follow-up, a total of 19 patients received up to 2 endoscopic VTP treatments. Of these patients, 42%, 32%, and 26% had at least 1 tumor in the renal pelvis, calyx, or the ureter, respectively, at baseline. Moreover, 36.8% of patients had solitary kidney and 31.6% of patients had a history of local treatment before enrolling on the study.

Seventy-four percent of patients (n = 14) received treatment at the MTD of 200 mW/cm. Two patients experienced dose-limiting toxicities in the form of grade 2 and 3 flank pain. The most common toxicities included transient flank pain (79%) and hematuria (84%). No treatment-related ureteral strictures were observed.

At 30 days, the response rate with this treatment approach was 94%, which was comprised of a complete response (CR) rate of 50% and a partial response rate of 44%. Eight patients received a second VTP, translating to a final CR rate of 68%. Notably, all patients had preserved kidney at 6 months of follow-up.

The phase 3 ENLIGHTED trial (NCT04620239) will enroll patients with new or recurrent low-grade, non-invasive UTUC who were at least 18 years of age. They need to have up to 2 biopsy-proven tumor lesions with low-grade involvement with the largest index tumor being 5 mm to 15 mm in diameter. These lesions need to be in the renal pelvis, ureter of the ipsilateral kidney, or the calyces. High-grade cells must be absent on cytology.

If patients have high-grade or muscle invasive urothelial carcinoma of the bladder, they will be excluded. Patients also cannot have current or prior carcinoma in situ in the upper urinary tract, nor can they have a history of invasive T2 or higher disease in the past 2 years.

After screening, patients will receive treatment on visit 1a. In the induction treatment phase, patients will undergo a visual tumor assessment at 1 month and if no tumor or non-treatable tumor was observed, they will undergo another assessment at 2 months. If visible and treatable tumor is observed, they will receive their second (visit 1b) or third (visit 1c) treatment with the drug. On visit 2, they will be evaluated for response. If they do not achieve a complete response, they will go on to receive standard-of-care (SOC) treatment. If they do, they will progress to the maintenance phase of the trial.

At 3 months, 6 months, and 9 months, visits 2a, 2b, and 2c will occur, respectively, and treatment will be given only if a new lesion outside of the treated area was observed. Up to 1 VTP was given if the lesion was in a treated area. If disease recurrence or progressive disease occurs, then patients will go on to receive SOC. At 12 months, visit 3 will occur, and this will signify the end of treatment. Patients will then enter a long-term follow-up phase ranging from 18 months to 60 months.

A primary objective of the early-phase trial was to evaluate the efficacy and durability of the treatment, and a key secondary objective was to examine the safety and tolerability of the approach.

At a data cutoff date of April 25, 2023, a total of 9 patients were enrolled to the trial and 5 received treatment with padeliporfin VTP. A total of 100 patients are anticipated to enrolled to the trial at 32 clinical sites in the United States, European Union, and Israel.

In April 2023, the DSMB reviewed the trial and recommended that the trial continue as planned.

References

1. ImPact Biotech receives FDA orphan drug designation for padeliporfin VTP in pancreatic cancer. News release. ImPact Biotech. July 5, 2023. Accessed July 5, 2023. https://www.globenewswire.com/news-release/2023/07/05/2699630/0/en/ImPact-Biotech-receives-FDA-Orphan-Drug-Designation-for-Padeliporfin-VTP-in-Pancreatic-Cancer.html
2. Coleman J, Margulis V, Scherz AJ, et al. A phase 3 multicenter study to evaluate the safety and efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in treatment of low-grade (LG) upper tract urothelial cancer (UTUC). J Clin Oncol. 2023;41(suppl 16):TPS4613. doi:10.1200/JCO.2023.41.16_suppl.TPS4613
3. FDA grants fast track designation to padeliporfin ImPACT for Steba biotech. News release. Steba Biotech. January 17, 2021. Accessed July 5, 2023. https://www.prnewswire.com/il/news-releases/fda-grants-fast-track-designation-to-padeliporfin-impact-for-steba-biotech-824291565.html