Update 20 November 2021
Houston, TX, Nov. 18, 2021 (GLOBE NEWSWIRE) — RadioMedix, a clinical-stage biotechnology company developing radiotheranostic drugs, announced that it has been awarded a $2.0M Direct to Phase II Small Business Innovation Research (SBIR) grant from the National Cancer Institute at the US National Institutes of Health. The grant supports Phase I/II clinical development of innovative alpha-emitter labeled peptide, AlphaMedixTM, for therapy of somatostatin receptor-positive neuroendocrine tumors.
RadioMedix successfully completed Phase I and Phase II NCI SBIR Contracts focused on the dose-escalation and safety studies of AlphaMedix in PRRT-naïve neuroendocrine patients. The Phase II SBIR funding will be used to evaluate the additional safety and efficacy of this investigational drug and expanded clinical indications of AlphaMedix™. These clinical studies are done in collaboration with our business partner, Orano Med.
“We witness the groundbreaking advances in nuclear medicine and targeted radiotherapy. RadioMedix is part of this movement and we have a strong commitment to introduce a new pipeline of alpha-emitter labeled drugs to the clinic”, said RadioMedix CSO, Izabela Tworowska, Ph.D. and Principal Investigator of the grant. “We would like to thank NCI SBIR for selection of this project for funding and continuation of their support of the targeted alpha-emitter therapy”, added Dr. Tworowska.
“The NCI SBIR funding will have a significant impact on the acceleration of the clinical studies of AlphaMedix and commercialization of this investigational drug”, said Ebrahim S Delpassand, MD, CEO of RadioMedix. “We are seeking additional funding from investors and venture capital firms to accelerate clinical development of our platform of alpha-emitter labeled drugs. We firmly believe that targeted alpha-emitter therapy will be a game-changer in responding to numerous unmet needs in oncology”, added Dr. Delpassand.
See Clinical Trial of 212Pb below.
What is Targeted Alpha-emitter Therapy?
Regular PRRT which is authorised for use now, i.e. Lutathera/Lu177 is a beta therapy. Targeted Alpha Therapy is based on the coupling of alpha particle emitting radioisotopes to tumour selective carrier molecules, such as monoclonal antibodies or peptides. These molecules have the ability to selectively target tumour cells even if they are spread throughout the body. They recognize the targeted cancer cells through antigens that are expressed on the cell surface and can bind selectively to these cells, similar a key fitting into a lock. In targeted alpha therapy these carrier molecules serve as vehicles to transport the radioisotopes to the cancer cells. This is called the “magic bullet” approach. Radioisotopes that emit alpha particles seem particularly promising to selectively destroy cancer cells. Alpha particles have a high energy in the range of 5-9 MeV and at the same time a very short path length in human tissue below 0.1 mm, corresponding to less than 10 cell diameters. Consequently, the use of alpha emitters allows the specific targeting and killing of individual malignant cells, while minimizing the toxicity to surrounding healthy tissue. Extracted from EU Science Hub
According to the clinical trials document, this drug addresses an unmet need in the field of peptide receptor radionuclide therapy (PRRT) for NETs. Substitution of an alpha emitter (²¹²Pb) for the beta emitters currently being used (i.e., 177Lu or 90Y) will provide significantly higher Linear Energy Transfer (LET) and a shorter path length. Higher LET particles should cause more tumor cell death. Shorter path length should result in less collateral damage of the normal tissue and therefore less side effects for subjects receiving the drug.
What is the difference between ‘regular’ PRRT and the Alpha version?
From the scant ‘patient understandable‘ information currently available, it would appear that alpha therapy has the potential to be more targeted and less toxic than beta PRRT – to me that seems like it would be able to target smaller tumours. I also noted that alpha therapy is sometimes described as a ‘radioimmuotherapy’ or ‘alpha immunotherapy’, indicating the mechanism of action is significantly different to that of conventional PRRT. It was also described as a ‘Trojan Horse’ which would seem to hint at its immunotherapy credentials. I noted that TAT is also being studied for use in Prostate Cancer and Leukaemia. The main effort for NETs is based on the use of two TAT radionuclides – 225Actinium and 212Pb
Clinical trials – 212Pb-AR-RMX
Update 3 Jan 2020. RadioMedix Inc. is pleased to announce that the company has been selected for the 2019-2020 Commercialization Accelerator Program (CAP) by the National Institute of Health (NIH) SBIR/STTR (Small Business Innovation Research/Small Business Technology Transfer) program office. This award is following our two-years, $2.0 M Phase II SBIR funded in part with Federal funds from the National Cancer Institute, National Institutes of Health and Human Services, under Contract No HHSN261201800048C. The Contract focuses on the clinical development of 212Pb-AlphaMedix™ for the targeted alpha-emitter therapy (TAT) of neuroendocrine tumours.
In 2018, RadioMedix Inc. and Orano Med initiated the Phase 1 trial for AlphaMedixTM in patients with somatostatin receptor (SSTR) positive Neuroendocrine Tumors (NETs) – an NIH supported trial.
AlphaMedixTM is composed of a somatostatin analogue radiolabeled with 212Pb, an isotope used for Targeted Alpha-emitter Therapy (TAT). This open-label, dose escalation study’s objective is to determine safety, bio-distribution, and preliminary effectiveness of 212 Pb-AR-RMX in adult patients with differentiated (sic) NETs. “Targeted Alpha-emitter Therapy (TAT) is the wave of the future in nuclear oncology and has a tremendous potential to treat patients with NET and overcome some of the limitations of current Peptide Receptor Radionuclide Therapy (PRRT)” said Dr. Ebrahim S. Delpassand, Chairman and CEO of RadioMedix, sponsor of the trial. They further announced on 21 Feb 2018 that the first patients had undergone some treatment.
Phase 1 Clinical Trial Document – Phase 1 Study of AlphaMedix™ in Adult Subjects With SSTR (+) NET – click here – Phase 2 document to follow when published.
Ornamed Website – click here
RadioMedix Inc Website – click here
Some advance info on the data from the Phase 1 trial results (quote from Dr Strosberg)
“Some exciting data on peptide receptor radionuclide therapy have been released with regard to the alpha particle–emitting isotope 212Pb–DOTATATE; this [treatment] was associated with exceptionally high response rates with the maximum-tolerated dose, which was discovered in the phase 1 study. Alpha emission is completely different from beta-emitting [radionuclide therapy], such as lutetium-177 (Lutathera)or yttrium-90; it delivers a much higher energy over a much shorter particle length. Although development may take more than a few years, I believe this [approach] has the potential to improve the therapeutic index that we are currently seeing with lutetium-177” Read the quote reference here.
This has been taken from the Radiomedix website:
This summary was presented at ASCO 2021 as an abstract:
DOI: 10.1200/JCO.2021.39.15_suppl.4117 Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021) 4117-4117.
Conclusions: This F-I-H clinical study of AlphaMedix shows that PRRT with 212Pb is feasible, well tolerated, and provides substantial reduction in tumor burden to patients with unresectable, metastatic SSTR-expressing NETs. Dramatic improvement in tumor burden and a positive impact on quality of life were seen in all of the PRRT naïve subjects who AlphaMedix at the highest dose tested.
Clinical trials – 225Ac
There seems to be quite a bit of use in India, not much is known if the Indian Drug Approval authorities have authorised it or it’s being used on a clinical trial basis. Anecdotally being used in German studies too. Searching “AC225” on the clinical trials database brings up trials in prostate, colorectal and melanoma only.
However, I did find this from the same company involved in the 212Pb trial above. “Excel Diagnostics and Nuclear Oncology Center Announces FDA Authorization of IND for 225Ac-PSMA I&T Targeted Alpha Therapy for Castration Resistant Prostate Cancer. This would be in line with my searches above”.
Targeted Alpha Theranostics
Read about the involvement of Viewpoint Molecular Targeting (VMT) who are involved in a theranostic approach using TAT. Presumably working with alongside Radiomedix 212Pb approach. Read more here:
Interest point – Cu64 Dotatate PET for NETs
The same company is involved is this now approved somatostatin receptor PET for NETs.
Clinical Trials Disclaimer
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided in the clinical trials document. It’s very important to check the trial inclusion and exclusion criteria before making any contact.
Inclusion of any trial within this blog should not be taken as a recommendation by Ronny Allan.
Subscribe to my newsletter
Thanks for reading.
Sign up for my newsletters – Click Here