US FDA Grants PV-10 Orphan Drug Designation for Neuroblastoma

Monday November 5, 2018

 

KNOXVILLE, TN, /GLOBE NEWSWIRE/ -- Provectus (OTCQB: PVCT) today announced that the Company was granted orphan drug designation (ODD) by the U.S. Food and Drug Administration (FDA) for small molecule oncolytic immunotherapy PV-10 for the treatment of neuroblastoma, a non-central nervous system (CNS) pediatric solid tumor. Intratumoral injection of PV-10 can yield immunogenic cell death (ICD) in solid tumor cancers and stimulate tumor-specific reactivity in circulating T cells.1-4

Neuroblastoma forms from immature nerve cells and usually begins in the adrenal glands. It may also begin in the abdomen, chest, or near the spine. Neuroblastoma most often occurs in children younger than 5 years of age, and presents when the tumor grows and causes symptoms. According to the National Cancer Institute SEER Cancer Statistics Review 1975-2015, the 5-year survival among children 0 to 19 years of age is 75.2%.5

Initial non-clinical testing of PV-10 in treatment-refractory neuroblastoma has closely paralleled previous non-clinical and clinical study of PV-10 for murine and human adult solid tumors, at both the tumor (selective destruction of injected tumors) and cellular (ICD) levels.6 Non-clinical investigation by member institutions of the Pediatric Oncology Experimental Therapeutics Investigators' Consortium (POETIC) has confirmed that ICD also occurs in neuroblastoma.

The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US. ODD status qualifies companies for benefits that include seven years of market exclusivity following marketing approval, tax credits on U.S. clinical trials, eligibility for orphan drug grants, and waiver of certain administrative fees.

ODD status previously was granted to PV-10 for the treatments of metastatic melanoma in 2007 and hepatocellular carcinoma (HCC) in 2013.

About Neuroblastoma

If detected at an early stage, surgery is the definitive treatment. Once neuroblastoma has recurred or spread from the primary site, therapeutic options are limited principally to chemotherapy or clinical trial.7 A recent review of emerging treatment options for neuroblastoma noted that "less than 50% of patients with high-risk neuroblastoma will survive long-term with current therapies, and survivors are at risk for serious treatment-related late toxicities."8

Therapeutic options include high-dose systemic chemotherapy with alkylating agents, radiation therapy, experimental treatments like regional therapy, or immunotherapy. Unlike many adult solid tumor types, pediatric solid tumors have largely proven unresponsive to immune checkpoint inhibitors such as anti-PD-1 antibodies. A recent Phase 2 study of pembrolizumab in pediatric solid tumors showed that less than 20% of patients tested were candidates for anti-PD-1 therapy based on low expression of the PD-L1 biomarker, and no candidates achieved an objective response.9

About PV-10

Provectus' lead investigational oncology drug product, PV-10, the first small molecule oncolytic immunotherapy, can induce immunogenic cell death. PV-10 is undergoing clinical study for adult solid tumor cancers, like melanoma and cancers of the liver, and preclinical study for pediatric cancers.

About the Pediatric Oncology Experimental Therapeutics Investigators' Consortium

The Pediatric Oncology Experimental Therapeutics Investigators' Consortium (POETIC) was founded in February 2003 by Dr. Tanya Trippett at Memorial Sloan Kettering Cancer Center and Dr. Lia Gore at the University of Colorado Cancer Center. POETIC is composed of ten large academic medical centers in North America with a major emphasis on comprehensive cancer care and research that provide the collaborative and research strength needed to complete intensive phase I and II studies. Each of the institutions is uniquely suited to complete early studies in the pediatric and adolescent populations. POETIC's assets include membership in NCI-designated Comprehensive Cancer Centers, on-site NIH-funded pediatric and/or general clinical translational research centers (CTRCs/CTSAs), and active collaborations with developmental therapeutics programs for adults at a majority of its member institutions. The availability of strong basic science and translational research programs at the institutions allows focus on the development and evaluation of new therapeutic strategies for patients with cancer and related disorders. POETIC's pediatric oncology studies focus on the biologic basis for anti-cancer therapy, and in particular, attempt to explore and evaluate novel agents and/or combinations of therapies early in clinical development as well as new approaches to targeted delivery. For additional information about POETIC, please visit the Consortium's website at www.poeticphase1.org.

About Provectus

Provectus Biopharmaceuticals, Inc. (Provectus or the Company) is a clinical-stage biotechnology company leading the development of a new class of drugs based on halogenated xanthenes, which are chemical small molecules. Information about the Company's clinical trials can be found at the NIH registry, www.clinicaltrials.gov. For additional information about Provectus, please visit the Company's website at www.provectusbio.com.

References

  1. Wachter et al. Functional Imaging of Photosensitizers using Multiphoton Microscopy. Proceedings of SPIE 4620, 143, 2002.
  2. Liu et al. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget 7, 37893, 2016.
  3. Qin et al. Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death. Cell Death and Disease 8, e2584, 2017.
  4. Liu et al. T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model. PLoS One 13, e0196033, 2018
  5. Noone et al. (eds). SEER Cancer Statistics Review, 1975-2015. National Cancer Institute. Bethesda, MD, based on November 2017 SEER data submission, posted to the SEER web site, April 2018. Table 28.8.
  6. Swift et al. In vitro and xenograft anti-tumor activity, target modulation and drug synergy studies of PV-10 against refractory pediatric solid tumors. Journal of Clinical Oncology 36, no. 15_suppl, 10557, 2018.
  7. PDQ Pediatric Treatment Editorial Board. Neuroblastoma Treatment (PDQ®): Health Professional Version. 2018 Aug 17. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002-.
  8. Applebaum et al. Emerging and investigational therapies for neuroblastoma. Expert Opinion on Orphan Drugs 5(4):355, 2017.
  9. Geoerger et al. KEYNOTE-051: An update on the phase 2 results of pembrolizumab (pembro) in pediatric patients (pts) with advanced melanoma or a PD-L1–positive advanced, relapsed or refractory solid tumor or lymphoma. Journal of Clinical Oncology 36, no. 15_suppl, 10525, 2018.

FORWARD-LOOKING STATEMENTS: This release contains "forward-looking statements" as defined under U.S. federal securities laws. These statements reflect management's current knowledge, assumptions, beliefs, estimates, and expectations and express management's current views of future performance, results, and trends and may be identified by their use of terms such as "anticipate," "believe," "would," "could," "estimate," "expect," "intend," "may," "plan," "predict," "project," "will," and other similar terms. Forward-looking statements are subject to a number of risks and uncertainties that could cause our actual results to materially differ from those described in the forward-looking statements. Readers should not place undue reliance on forward-looking statements. Such statements are made as of the date hereof, and we undertake no obligation to update such statements after this date.

Risks and uncertainties that could cause our actual results to materially differ from those described in forward-looking statements include those discussed in our filings with the Securities and Exchange Commission (including those described in Item 1A of our Annual Report on Form 10-K for the year ended December 31, 2017).

Contact:

Provectus Biopharmaceuticals, Inc.
Tim Scott, Ph.D.
President
Phone: 866-594-5999

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