|[January 24, 2014]
Provectus's PV-10 Path to Initial Approval in U.S. Now Clear Per FDA Meeting Minutes
KNOXVILLE, Tenn. --(Business Wire)--
Provectus Biopharmaceuticals, Inc. (PVCT)
a development-stage oncology and dermatology biopharmaceutical company,
today announced that it has received the official minutes from the Type
C meeting held with the FDA's Division of Oncology Products 2 on
December 16, 2013. The purpose of the meeting was to determine which of
the available paths that Provectus's novel investigational oncology drug
PV-10 will take in pursuit of initial FDA approval and
commercialization. PV-10, a 10% solution of rose bengal disodium, is
designed to selectively target and destroy cancer cells without harming
surrounding healthy tissue, while inducing a secondary tumor-specific
immune response. As a result of this meeting, Provectus will submit data
from its Phase 2 study in a formal breakthrough therapy designation
(BTD) request this quarter, and should receive a decision within 60 days
of receipt of that request.
With the passage of the Food and Drug Administration Safety and
Innovation Act (FDASIA) in July 2012, the Food and Drug Administration
(FDA) was given powerful expedited tools to speed patient access to
innovative medicines for serious or life-threatening conditions (Food
and Drug Administration Safety and Innovation Act (FDASIA)). FDASIA
initiatives such as breakthrough therapy designation are designed to
accelerate approval for new drugs that show preliminary clinical
evidence of a large treatment effect. A key feature of BTD authorizes
the Agency to take steps to ensure that the design of the clinical
trials are as efficient as practicable, when scientifically appropriate,
such as by minimizing the number of patients exposed to a potentially
less efficacious treatment. Requests for BTD are reviewed and granted or
rejected within 60 days of receipt. As Provectus has previously
reported, based on rapid tumor destruction in a positive Phase 2 trial
in melanoma patients receiving PV-10 (protocol PV-10-MM-02), input from
the Agency regarding the current development plan was sought. Agency
Asked Questions: Breakthrough Therapies) encourages sponsors to seek
such advice prior to formal request for designation.
Chief Executive Officer Craig Dees, Ph.D., observed, "This meeting with
the FDA is another significant step forward in streamlining the pathway
to initial U.S. approval of PV-10 s the first local agent for recurrent
locoregionally advanced melanoma. These patients suffer with
troublesome, disfiguring disease that can persist for many years before
presenting at distant sites. Our meeting with the Agency established the
parameters for submission of a BTD request tailored to addressing the
pressing needs of these patients. We're grateful that our work with the
Agency, in this and in our previous meetings, to identify a strategy for
demonstration of clinical benefit in recurrent patients is bearing
fruit. We are very pleased that the path to initial approval in the U.S.
is now clear and PV-10 can be available to help patients in a more
condensed time frame than if the Agency required an overall survival
endpoint in a large randomized Phase 3 study."
The meeting and official meeting minutes provided valuable guidance on a
number of issues surrounding the approval path of PV-10:
The Agency agreed with Provectus that treatment of cutaneous and
subcutaneous tumors in patients with locally advanced cutaneous
melanoma (i.e., recurrent, in-transit or satellite melanoma that has
not yet spread from the skin to distant sites) could provide clinical
benefit to such patients, particularly if the measured objective
responses in patients' disease correlated to a demonstrated treatment
effect on one or more symptoms of their disease (e.g., pain, infection
or significant bleeding).
The Agency agreed to work with Provectus to quantify symptom control
in this patient population.
In reference to discussions on the potential for breakthrough therapy
designation, "FDA advised Provectus to provide objective response
rates with adequate information to evaluate the symptomatic treatment
effects (e.g. pain, infection, bleeding) in patients presenting with
locally advanced cutaneous melanoma who received PV-10 to all lesions."
The Phase 2 study of PV-10 showed:
Among all 80 intent-to-treat melanoma patients, 26% achieved a
complete response and another 25% achieved a partial response
(shrinkage by at least 30%) of their injected study tumors (51%
objective response rate, confidence interval 40-63%).
In the subgroup of melanoma patients that received PV-10 injection
into all known disease (28 of the 80 ITT (News - Alert) patients), 50% achieved a
complete response (71% ORR, CI 51-87%).
In the subgroup of melanoma patients with locally advanced cutaneous
melanoma that received PV-10 injection into all known disease or only
had 1 or 2 designated bystander tumors untreated (54 of the 80 ITT
patients), a complete response was achieved in 232 of 363 injected
tumors (64% of lesions) with the vast majority of these tumors
requiring only 1 or 2 injections.
These data show that if a tumor is accessible to PV-10 injection, the
drug is likely to destroy that tumor. If approved, PV-10 would be the
first tissue-sparing local therapy for recurrent melanoma.
Dees continued, "The Agency may yet recommend and it may be in the best
interest of Provectus to undertake a small, short bridging study in
patients where all tumor burden can be injected. This would allow more
frequent dosing than was permitted in the Phase 2 study, presumably akin
to the dosing schedule currently used to treat nearly 100 patients under
our expanded access protocol, and allow symptomatic endpoints to be
prospectively correlated with objective response criteria. Provectus has
$18 million in cash reserves and would not require additional capital or
the resources of a partner to conduct such a study. If such a study is
conducted, it also fits with needs for an international study supportive
of licensure in Australia, Europe, China and India."
Dees further stated, "Non-specific local treatments that temporarily
reduce tumor burden, such as surgery and radiation, are the most
commonly used cancer therapies today. Furthermore, we believe our
clinical and immunologic mechanism data show that it may be possible to
delay or prevent melanoma metastasis to distant sites."
Dees continued, "Measurement of tumor shrinkage via objective response
criteria has been considered direct clinical benefit in drug approvals
for other skin cancers and we believe a similar case can be made for
PV-10 in locally advanced cutaneous melanoma. As advised by the Agency,
we will submit data from the 28 patients in our Phase 2 study who had
all existing disease treated in a formal BTD request this quarter, and
should receive a decision within 60 days of receipt of that request."
Dees concluded, "While the rapid ablative effect immediately evident in
patients treated with PV-10 highlights our path to initial approval, the
bystander effect continues to be of scientific interest and studies to
quantify systemic tumor-specific immune response in cancer patients are
ongoing. This emerging understanding of the secondary effect of tumor
ablation with PV-10 is an important foundation for future studies to
assess the long-term impact of PV-10 on distant metastasis and possible
combination strategies for use of PV-10 in the treatment of cancer
patients with more advanced disease."
About Provectus Biopharmaceuticals, Inc.
Provectus Biopharmaceuticals specializes in developing oncology and
dermatology therapies. Its novel oncology drug PV-10 is designed to
selectively target and destroy cancer cells without harming surrounding
healthy tissue, significantly reducing potential for systemic side
effects. Its oncology focus is on melanoma, breast cancer and cancers of
the liver. The Company has received orphan drug designations from the
FDA for its melanoma and hepatocellular carcinoma indications. Its
dermatological drug PH-10 also targets abnormal or diseased cells, with
the current focus on psoriasis and atopic dermatitis. Provectus has
recently completed Phase 2 trials of PV-10 as a therapy for metastatic
melanoma, and of PH-10 as a topical treatment for atopic dermatitis and
psoriasis. Information about these and the Company's other 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.pvct.com
or contact Porter, LeVay & Rose, Inc.
FORWARD-LOOKING STATEMENTS: The forward-looking statements contained
herein are subject to certain risks and uncertainties that could cause
actual results to differ materially from those reflected in the
forward-looking statements. Readers are cautioned not to place undue
reliance on these forward-looking statements, which reflect management's
analysis only as of the date hereof. The company undertakes no
obligation to publicly revise these forward-looking statements to
reflect events or circumstances that arise after the date thereof.
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