SYDNEY, Aug. 7, 2020 /PRNewswire/ -- Kazia
Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian
oncology-focused biotechnology company, is pleased to announce that
the United States Food and Drug Administration (FDA) has awarded
Rare Pediatric Disease Designation (RPDD) to Kazia's paxalisib
(formerly GDC-0084) for the treatment of Diffuse Intrinsic Pontine
Glioma (DIPG), a rare and highly-aggressive childhood brain
cancer.
Key Points
- With RPDD granted, Kazia may now be eligible to receive a 'rare
pediatric disease priority review voucher' (PRV) if paxalisib is
approved for DIPG
- A PRV grants the holder an expedited six-month review of a new
drug application by FDA. PRVs can be sold to other companies and
have historically commanded prices between US$68 million and US$350
million
- RPDD has been awarded following positive emerging preclinical
data in DIPG, and with initial clinical efficacy data expected in
2H CY2020; positive clinical data may substantially enhance
likelihood of a potential future PRV
The FDA's RPDD program is intended to advance the development of
drugs and biologics for certain serious and life-threatening rare
pediatric diseases by providing incentives to industry. Most
significant among these incentives is the potential access a
priority review voucher at the time of a marketing authorization
for the rare paediatric disease.
Kazia CEO, Dr James Garner,
commented, "although glioblastoma remains our primary focus for
paxalisib, we have been devoting increasing energy to developing
the drug in childhood brain cancer as well. For patients diagnosed
with DIPG, there are currently no FDA-approved drug treatments, and
the average survival from diagnosis is around 9.5 months. The
granting of RPDD by the FDA recognises our efforts and achievements
so far and leaves us well placed to move paxalisib forward as a
potential therapy for DIPG. We continue to be inspired by the
dedication of our collaborators in this field and are committed to
understanding whether paxalisib may be able to help in this
enormously challenging paediatric disease."
Rare Pediatric Disease Designation
The Food and Drug Administration Safety and Innovation Act
(2012) established FDA's RPDD initiative. RPDD may be granted to
drugs in development for diseases which primarily affect children
(under the age of 18 years), have an incidence of less than 200,000
new cases per annum in the United
States, and which are serious or life-threatening.
A sponsor of a drug with RPDD may request a Rare Pediatric
Disease Priority Review Voucher (PRV) at the time of a marketing
application to FDA. In effect, the PRV shortens the FDA review
period for a future marketing application of any drug from 12
months to 6 months. PRVs can be sold to other companies and have
historically been transacted at prices in the tens to hundreds of
millions of dollars. For a large company launching a billion-dollar
drug, the six-month acceleration in regulatory review can be of
substantial economic value. In 2019, five pediatric PRVs were
granted by FDA.
Phase I Clinical Trial in DIPG
In October 2018, St Jude
Children's Research Hospital in Memphis,
TN commenced a phase I clinical trial of paxalisib in DIPG
(NCT03696355). This study reported favourable top-line safety data
in September 2019 and established 27
mg/m2 as the maximum tolerated dose for paediatric use.
The study has completed recruitment, and initial efficacy data is
anticipated during the second half of calendar 2020. This data will
be used to guide future development of paxalisib in this
disease.
Preclinical Research in DIPG
Dr Matt Dun and colleagues at the
University of Newcastle, Australia
have conducted extensive laboratory research with paxalisib,
focused on phosphoproteomic analysis of its activity in DIPG cell
lines. Phosphoproteomics is a new approach in cancer research that
attempts to discern how complex signaling pathways are modified in
tumours. Work at the Dun laboratory has shown paxalisib to be
broadly active in DIPG and has identified a number of potential
combination strategies which may enhance its activity. Initial data
was presented at the Society for Neuro-Oncology (SNO) Pediatric
Neuro-Oncology Basic and Translational Research Conference in
San Francisco, CA, in May 2019.[1] Further ongoing work in
animal models is expected to provide additional insight.
In parallel, related laboratory research is underway in the DMG
Research Center at the University of Zurich, Switzerland, under the leadership of
Dr Javad Nazarian. Dr Nazarian is
also the principal investigator at Center for Genetic Medicine within the
Children's National Medical Center,
Washington DC with a focus on DIPG. Laboratory
research is also being conducted at St Jude Children's Research
Hospital by Dr Chris Tinkle and Dr
Suzanne Baker and colleagues, in
parallel to the ongoing phase I clinical trial at that center.
Next Steps
Kazia anticipates that initial efficacy data from the ongoing
phase I study at St Jude will be available during 2H CY2020. Future
clinical research directions will be determined on the basis of
this data, in close consultation with collaborators.
About Kazia Therapeutics Limited
Kazia Therapeutics Limited (ASX: KZA, NASDAQ: KZIA) is an
innovative oncology-focused biotechnology company, based in
Sydney, Australia. Our pipeline
includes two clinical-stage drug development candidates, and we are
working to develop therapies across a range of oncology
indications.
Our lead program is paxalisib (formerly GDC-0084), a small
molecule inhibitor of the PI3K / AKT / mTOR pathway, which is being
developed to treat glioblastoma, the most common and most
aggressive form of primary brain cancer in adults. Licensed from
Genentech in late 2016, paxalisib entered a phase II clinical trial
in 2018. Interim data was reported most recently at AACR in
June 2020, and further data is
expected in 2H 2020. Paxalisib was granted orphan designation for
glioblastoma by the US FDA in February
2018, and rare pediatric disease designation for DIPG in
August 2020.
TRX-E-002-1 (Cantrixil), is a third-generation benzopyran
molecule with activity against cancer stem cells and is being
developed to treat ovarian cancer. TRX-E-002-1 has completed a
phase I clinical trial in Australia and the
United States with the final data expected in the second
half of calendar 2020. Interim data was presented most recently at
the AACR conference in June 2020.
Cantrixil was granted orphan designation for ovarian cancer by the
US FDA in April 2015.
This document was authorized for release to the ASX by
James Garner, Chief Executive
Officer, Managing Director.
[1] R Duchatel et al. (2019) Neuro-Oncology,
21(Suppl.2):ii68
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