SYDNEY, July 6, 2023
/PRNewswire/ -- Kazia Therapeutics Limited (NASDAQ: KZIA; ASX:
KZA), an oncology-focused drug development company, is pleased to
announce that its lead program, paxalisib, has been awarded Fast
Track Designation (FTD) by the United States Food and Drug
Administration (FDA) for the treatment of solid tumor brain
metastases harboring PI3K pathway mutations in combination with
radiation therapy.
The FDA's decision to grant FTD was based on promising clinical
data from an interim analysis of an ongoing Phase 1 clinical trial
in which patients with brain metastases from a primary tumour are
receiving paxalisib in combination with radiotherapy (NCT04192981).
These clinical data were presented at the 2022 Annual Conference on
CNS Clinical Trials and Brain Metastases, jointly organized by the
Society for Neuro-Oncology (SNO) and the American Society for
Clinical Oncology (ASCO), by Dr. Jonathan
Yang, lead investigator in the clinical trial. All
nine evaluable patients in the trial (100%) responded to the
combination of paxalisib with radiotherapy. Published benchmarks
suggest a typical response rate for radiotherapy alone to be around
20-40%.
Key Points
- FTD is designed to expedite development of pharmaceutical
products which demonstrate the potential to address unmet medical
needs in serious or life-threatening conditions.
- FTD provides Kazia with enhanced access to FDA, including
opportunities for face-to-face meetings and written consultation
throughout the remaining development of paxalisib. Drugs granted
FTD may also be eligible for Accelerated Approval and Priority
Review, which may result in faster product approval.
- Paxalisib was previously granted FTD for glioblastoma in
August 2020, giving paxalisib now two
largely independent opportunities to access the benefits of this
designation.
"Brain metastases are rapidly emerging as a key pillar of
paxalisib's clinical development," said Dr. John Friend, Chief Executive Officer of Kazia.
"We have seen a high level of interest from clinicians in the
emerging data from this patient population, and it is exciting to
now have that interest complemented by FDA's award of Fast Track
Designation. With important data read-outs expected in adult and
childhood brain cancer during CY2023, we will be working with
investigators and advisors to drive forward our research in brain
metastases also."
Brain Metastases
Brain metastases are a common complication of many tumours, but
are particularly common in breast cancer, lung cancer, and
melanoma. Brain metastases are typically highly resistant to
treatment and survival rates are generally low. More than 250,000
patients are diagnosed with brain metastases each year in
the United States alone.
Radiotherapy is a common treatment modality for brain
metastases. Despite some efficacy, patients typically become
resistant over time, and repeat courses of radiotherapy can be
associated with significant neurological toxicity.
Expansion of Paxalisib Brain Metastases Study
The Phase I study (NCT04192981)is evaluating the safety and
efficacy of paxalisib in combination with whole brain radiotherapy
(WBRT) in patients with brain metastases and leptomeningeal
metastases from any primary tumour (cancer that has spread to the
brain from elsewhere in the body). The study was designed and
initiated by Dr. Jonathan Yang, when
he was at Memorial Sloan Kettering Cancer Center in New York, NY.
The study was designed in two stages. The first stage aimed to
recruit 12 patients and was intended to establish the maximum
tolerated dose (MTD) for paxalisib in conjunction with WBRT.
Subject to positive results in the first stage, the study includes
a second stage to assess initial efficacy signals and establish
whether further development is warranted.
The results of the first stage of the study were reported at the
SNO / ASCO 2022 Annual Conference on CNS Trials and Brain
Metastases in August 2022. The
combination was reported to be generally well-tolerated, with all
nine evaluable patients showing evidence of clinical response.
Recruitment of the second stage commenced in 2H CY2022. The
study is now open at two additional clinical sites: Miami Cancer
Institute in Miami, FL, and the
Fred Hutchinson Cancer Center in Seattle,
WA, where Dr. Yang is now based.
Fast Track Designation
Introduced under the FDA Modernization Act (1997), FTD may be
awarded by FDA to investigational drugs which are intended to treat
a serious or life-threatening condition, and which fill an unmet
medical need. FTD must be requested by the sponsor company and must
be accompanied by a detailed review of both preclinical and
clinical data. To be awarded FTD, drugs must generally be able to
show some potential advantage over existing therapies, either in
terms of safety or efficacy.
The key benefits of FTD comprise enhanced access to FDA, with
regular and more frequent opportunities for consultation and
discussion. In addition, drugs with FTD may be eligible for
Accelerated Approval, in which a new medicine is approved based on
a surrogate endpoint, and Priority Review, in which the standard
12-month review process may be reduced to eight months. Drugs with
FTD may also receive a 'rolling review' of their NDA submission, in
which sections are submitted for review as they become available,
potentially expediting the approval process.
Next Steps
Further data from the ongoing Phase 1 study is expected in 1Q
CY2024. Kazia continues to hold discussions with clinicians and
advisors regarding the potential design of a registrational study
in this indication.
Paxalisib is also the subject of nine other ongoing clinical
trials, including the pivotal GBM AGILE study in glioblastoma,
which is expected to provide final data in 2H CY2023, and a phase
II study in pediatric patients with diffuse midline gliomas, which
is expected to provide initial data in 3Q CY2023.
About Kazia Therapeutics Limited
Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA) is an
oncology-focused drug development company, based in Sydney, Australia.
Our lead program is paxalisib, a brain-penetrant inhibitor of
the PI3K / Akt / mTOR pathway, which is being developed to treat
multiple forms of brain cancer. Licensed from Genentech in late
2016, paxalisib is or has been the subject of ten clinical trials
in this disease. A completed Phase II study in glioblastoma
reported promising signals of clinical activity in 2021, and a
pivotal study in glioblastoma, GBM AGILE, is ongoing, with final
data expected in CY2023. Other clinical trials are ongoing in brain
metastases, diffuse midline gliomas, and primary CNS lymphoma, with
several of these having reported encouraging interim data.
Paxalisib was granted Orphan Drug Designation for glioblastoma
by the FDA in February 2018, and Fast
Track Designation for glioblastoma by the FDA in August 2020. In addition, paxalisib was granted
Rare Pediatric Disease Designation and Orphan Drug Designation by
the FDA for diffuse intrinsic pontine glioma in August 2020, and for atypical teratoid / rhabdoid
tumours (AT/RT) in June 2022 and
July 2022, respectively.
Kazia is also developing EVT801, a small-molecule inhibitor of
VEGFR3, which was licensed from Evotec SE in April 2021. Preclinical data has shown EVT801 to
be active against a broad range of tumour types and has provided
compelling evidence of synergy with immuno-oncology agents. A Phase
I study commenced recruitment in November
2021.
For more information, please visit www.kaziatherapeutics.com or
follow us on Twitter @KaziaTx.
This document was authorized for release by John Friend, MD, Chief Executive Officer.
Forward-Looking Statements
This announcement may contain forward-looking statements, which
can generally be identified as such by the use of words such as
"may," "will," "estimate," "future," "forward," "anticipate," or
other similar words. Any statement describing Kazia's future plans,
strategies, intentions, expectations, objectives, goals or
prospects, and other statements that are not historical facts, are
also forward-looking statements, including, but not limited to,
statements regarding: the timing for results and data related to
Kazia's clinical and preclinical trials, including
NCT04192981, and Kazia's strategy and plans with respect to
its programs, including paxalisib. Such statements are based on
Kazia's current expectations and projections about future events
and future trends affecting its business and are subject to certain
risks and uncertainties that could cause actual results to differ
materially from those anticipated in the forward-looking
statements, including risks and uncertainties: associated with
clinical and preclinical trials and product development, related to
regulatory approvals, and related to the impact of global economic
conditions. These and other risks and uncertainties are described
more fully in Kazia's Annual Report, filed on form 20-F with the
United States Securities and Exchange Commission, and in subsequent
filings with the SEC. Kazia undertakes no obligation to publicly
update any forward-looking statement, whether as a result of new
information, future events, or otherwise, except as required under
applicable law. You should not place undue reliance on these
forward-looking statements, which apply only as of the date of this
announcement.
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