Sperling Prostate Center

FDA Vetoes Photodynamic/TOOKAD Focal Therapy for Prostate Cancer

The often-quoted “Hope springs eternal in the human breast” was penned by the 18th century poet Alexander Pope. It certainly to developing new approaches to conquering prostate cancer (PCa). The greatest challenge to optimism may be the situation of men with metastatic castration-resistant PCa who hope for a breakthrough lifesaving cure while experimental immunotherapies and vaccines are buying them more time. However, even men newly diagnosed with localized, low-risk PCa nurture the hope for a minimalist treatment that will destroy the tumor, spare urinary/sexual functions, and allow them to return to normal life in a matter of days. Thus, no matter what the PCa grade and stage, surely every PCa patient harbors some degree of hope in his heart.

Clinical researchers and scientist also have hope

Hope for a revolutionary treatment is not just the province of patients. The research and development departments of pharmaceutical companies, device manufacturers, and academic science centers pursue their work with high hopes of creating a universal cure, or at least a safe and effective novel treatment for some particular PCa type.

A new photodynamic focal therapy for Prostate Cancer

A promisingly original method of focusing treatment on one side of the gland has been developed by Steba Biotech, a biotechnology company headquartered in Belgium. It is truly novel because it uses a light-activated drug to destroy selective cancerous areas. The procedure is called vascular-targeted photodynamic therapy (VTP). Ten minutes after an IV injection of a light-sensitive drug called TOOKAD®, thin optic fibers are inserted into the cancerous area to apply laser light. The light penetrates the tissue for a short distance, and the TOOKAD infusion responds to it by producing “high levels of substances known as oxygen radicals, which cause the destruction of the vessels supplying blood to the cancer followed by rapid death of the cancer cells.”[i] The use of TOOKAD distinguishes VTP as a drug-based treatment, not a thermal ablation like Focal Laser Ablation (FLA).

Facing the FDA

When it comes to bringing a new drug or treatment to the U.S. marketplace, there are many hoops to jump through. A significant source of those hoops is the Food and Drug Administration (FDA), a government watchdog agency charged with protecting patient safety. No matter how safe and effective a novel treatment appears in laboratory/animal testing, to win FDA approval it must survive a proving ground of clinical trials. This process involves arduous and expensive steps:

  1. One or more sponsors are identified to bear the costs of the trial
  2. Application is made to the FDA with information on the treatment, data from completed testing, and how the trial is to be designed and conducted
  3. If accepted, the trial is registered with ClinicalTrials.gov (National Institutes of Health)
  4. Recruitment into three successive testing phases begins, with more participants in each phase:
    • Phase I (safe dosage, side effects, initial effect on the cancer)
    • Phase II (further data to determine merit of moving to Phase III)
    • Phase III (large randomized study to validate earlier data against a comparator)

Investing in a trial requires confidence as well as hope on the part of the sponsor. However, once the Phase III results are in, there’s yet another application protocol to bring the treatment to market use.

Steba Biotech has long prepared to face the FDA approval process with VTP in phased clinical trials over several years. In 2017, Azzouzi et al.[ii] published 2-year follow-up results of a Phase III clinical trial comparing results on 206 low-risk PCa patients who had VTP vs. 207 low-risk PCa patients who went on Active Surveillance (AS). The authors reported that 6% of the VTP group had gone on to definitive treatment compared with 32% of the AS group, and that three times as many in the VTP group had negative biopsies at 2 years. Further results from the same study were presented at the 2018 American Urology Association meeting: “At 4 years the conversion rates were 24% with VTP and 53% with active surveillance alone. Erectile function and urinary continence were similar in the two groups…”[iii]

FDA denies approval

Based on these results, Steba was optimistic. They confidently prepared and submitted a New Drug Approval (NDA) application to the FDA. Unfortunately, on February 26, 2020, their hopes were dashed. By a 13-2 vote, the FDA’s Oncologic Drugs Advisory Committee (ODAC) declined to recommend TOOKAD VTP for approval. According to a news report, “Questions about the therapy’s pivotal trial design, endpoints, missing data, and adverse events all contributed to the negative vote.”[iv]

At the moment, the situation appears somewhat bleak for VTP, but the panel’s decision is not the end of the story. The Steba team will use the feedback from the panel to regroup, and will tackle the approval process further down the line. After all, the decision was not a unanimous knock-out for VTP, nor a general blow to PCa focal therapy. This is not the first time a new prostate cancer treatment met with FDA resistance (for instance, check out HIFU’s tenacious appeals to the FDA), nor will it be the last.

After all, when it comes to patients and doctors within the PCa landscape, hope springs eternal.

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

[i] https://www.ema.europa.eu/en/documents/overview/tookad-epar-summary-public_en.pdf
[ii] Azzouzi AR, Vincendeau S, Barret E, Cicco A et al. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 2017 Feb;18(2):181-191.
[iii] Bankhead, Charles. “Phototherapy Delays Radical Prostate Cancer Tx,” Medpage Today, May 24, 2018. https://www.medpagetoday.com/meetingcoverage/aua/73089
[iv] Bankhead, Charles. “FDA Panel: Thumbs Down for Prostate Cancer Focal Therapy,” Medpage Today, Feb. 26, 2020. https://www.medpagetoday.com/hematologyoncology/prostatecancer/85096


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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