Veyonda (idronoxil, formerly NOX66)
. At a recent Skype consultation with my physician at Theranostics AU in preparation for upcoming Lu-PSMA-I&T treatments, I asked if there was any role for radiosensitizers to enhance treatment results. He replied that there is one: Veyonda, formerly NOX66. It is given as a suppository daily for a few weeks prior to low dose radiation; That it causes substantial increased anti-cancer effects of low-dose radiation and enhancing the abscopal immume response, which impacts tumor sites that were not even irradiated.
So my online research disclosed that this is an astonishingly interesting therapeutic agent when combined with radiation.
The results of the DARRT-1 trial have been published Dec 2, 2019. (Direct and Abscopal Response to Radiotherapy). (Some excerpts follow.)
Additionally there is another trial in the works to test Veyonda with Lu-PSMA treatments, the Australian LuPIN-1 Trial. (Summary also below.)
I have inquired and requested to see if I could receive a course or courses of Veyonda on a "compassionate use basis" (outside of the trial) for my upcoming Lu-PSMA treatment(s). No doubt it would be private pay.
noxopharm.com/site/PDF/3134...
noxopharm.com/site/PDF/2005...
noxopharm.com/site/PDF/3132...
"
The Company expects to receive the final Statistical
Report in March 2020 which will contain specific
details of the radiographic analysis, including the
extent of any partial responses and detailed
responses of both irradiated and non-irradiated
lesions.
Planning for the next stage of testing is underway
in collaboration with the Company’s Medical
Advisory Boards. This will be a double-blind,
control-arm, multi-national, Phase 2/Phase 3
adaptive study that the Company hopes will be the
final step to obtaining marketing approval. DARRT-
2/DARRT-3 will use 6 repeated cycles of treatment
with Veyonda , compared to the single treatment
cycle used in DARRT-1. The Company anticipates
that this could provide an additional anti-cancer
effect and with it, the potential for an increase in
the all-important overall survival endpoint.
Upcoming milestones include the lodgement of an
IND application for DARRT-2/DARRT-3 to the U.S.
A. FDA, as well as applications to a range of other
regulatory bodies including the EMA and TGA."
“This is exciting data that validates our confidence in
the future of the NOX66 DARRT treatment regimen.
NOX66 DARRT has delivered a very meaningful anticancer
effect in a high proportion of men, halting
progression of their disease and providing an average
80% reduction in their pain levels, including some
men becoming pain-free.”
Commentary by Noxopharm Executive Chairman
and CEO, Graham Kelly PhD:
"The context here is that men in DARRT-1 had late stage,
progressive disease and had exhausted all
available treatment options. In general, they were
experiencing considerable pain, had poor quality of
life, and had a life expectancy of about 6-8 months. In
this trial, 10 of 15 (66%) men at the conclusion of the
study had responded to treatment with stable disease
or better at 6-months following start of treatment (as
determined radiographically) and with significantly
lower pain levels."
"Trial data
data shows that adding Veyonda (NOX66) to
low-dose (20Gy) palliative radiotherapy applied to a
single lesion changed the course of disease to a
considerable degree in at least 66% of men, with a
halt to disease progression and high levels of pain
relief lasting at least for the 6-months of observation.
The study treated 25 men. At the end of study at 6-
months: 9 had withdrawn, died or been lost to follow-up.
16 completed the study of whom 15 were
measurable radiographically.
Across all 3 Veyonda dosages (® 400, 800, 1200 mg):
1/15 patient had a partial response, 9/15 had
stable disease and 5/15 had progressive disease,
giving an overall tumour response rate of 66%.
5/16 patients (31%) had a PSA Response (>50% fall
from baseline), with PSA reductions ranging from
61-98%.
10/16 patients (62%) had a Pain Response (>30%
fall from baseline), with falls ranging from 43-100%
(pain-free).
The trial’s primary end-point of safety was met with
no significant or dose-limiting toxicities.
The secondary end-point of efficacy very clearly was
achieved based on rates of PSA Response, Pain
Response and Tumour Response (RECIST) in a high
proportion of men."
The following is from the Noxopharm corporate presentation of June 6, 2019. It discusses the DARRT Trials program overall and the LuPIN-1 trial:
"About the DARRT program
The Company’s DARRT (Direct and Abscopal Response to Radiotherapy) Program is testing the ability of Veyonda to increase tumourresponse to
palliative dosages of radiotherapy.The DARRT treatment regimen entails a 5-day course of radiotherapy (20-30 Gy) in 5 fractionated dosages targeting a single tumour, with Veyonda administered daily for up to 3 weeks. The rationale of DARRT is to combine the radio-enhancing properties of Veyonda that stem from its inhibition of sphingosine-1-phosphate pro-survival functions, combined with its ability to stimulate the body’s first line immune defence cells against cancer. The clinical outcome being sought is greater shrinkage of irradiated tumours and shrinkage of non-irradiated tumours (abscopal response). The DARRT treatment regimen is being tested initially in prostate cancer, but in due course is to be extended into other forms of solid cancer that the Company believes will assist the Veyonda marketing approval process.
LuPIN-1 trial of Veyonda with Lu-PSMA-617 in mCRPC (Australia)
LuPIN-1 is a dose escalation and dose expansion trial of men with mCRPC progressing despite having received docetaxel, cabazitaxel and either abiraterone or enzalutamide. All men enrolled are being administered up to 6 cycles of 177Lu-PSMA-617 at six-weekly intervals. The first eight men received 400 mg of Veyonda daily on days 1-10 of each cycle. Following a safety data review, the dose for patients 9-16 was escalated to 800 mg of Veyonda. Once the next safety data review of these 8 patients treated with 800 mg was concluded, an additional 16 patients were recruited at this dose, bringing the total patients recruited to 32 (8 x 400 mg, 24 x 800 mg). The trial now will enroll 56 men."
From the NCI Drug Dictionary:
idronoxil
A synthetic flavonoid derivative. Idronoxil activates the mitochondrial caspase system, inhibits X-linked inhibitor of apoptosis (XIAP), and disrupts FLICE inhibitory protein (FLIP) expression, resulting in tumor cell apoptosis. This agent also inhibits DNA topoisomerase II by stabilizing the cleavable complex, thereby preventing DNA replication and resulting in tumor cell death.
idronoxil suppository NOX66
A proprietary, suppository-based formulation composed of idronoxil, a synthetic flavonoid derivative, surrounded by a proprietary lipid that protects idronoxil from phase 2 degradation, with potential chemo- and radio-sensitizing activities. Upon administration, idronoxil blocks the activity of ecto-NOX disulfide-thiol exchanger 2 (ENOX2; tNOX), a tumor-specific external NADH oxidase that maintains the transmembrane electron potential across the plasma membrane and is overexpressed in certain cancer cell types while absent in normal, healthy cells. Loss of this potential directly inhibits certain pro-survival signal transduction pathways, such as the PARP1/PI3 kinase/Akt signaling pathway. The inhibition of these pathways prevents resistance to standard chemo- and radio-therapy and makes tumor cells more susceptible to the anti-tumor activity of conventional chemotherapeutic agents and radiotherapy. The formulation prevents detoxification of idronoxil to an inactive form by bypassing phase 2 metabolism; this increases idronoxil’s bioavailability as compared to idronoxil alone.
Note: There are no clinical trials of idronoxil (Veyonda) in the USA currently.
Six cycles of Lu-177 treatment
Help please
Pluvicto after long time androgen deprivation therapy
