Delving into the Latest Updates on AvidinOx-Lu-177-DOTA-Biotin with Synapse

Overview

Basic Info

Drug Type

Radionuclide Drug Conjugates (RDC), Therapeutic radiopharmaceuticals

Synonyms

AvidinOX, AvidinOx-Lu-177-DOTA, Oxidised Avidin

+ [6]

Target-

Mechanism

Ionising radiation emitters

Therapeutic Areas

NeoplasmsImmune System DiseasesDigestive System Disorders+ [1]

Active Indication

Colorectal CancerLymphoma

Inactive Indication

Colorectal Liver MetastasesLiver CancerLiver metastases+ [2]

Originator Organization

Sigma-Tau BV

Active Organization

Sigma-Tau BV

Inactive Organization

Alfasigma SpA

Sigma-Tau Industrie Farmaceutiche Riunite SpA

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure

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A Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Dosimetry, Maximum Tolerated Dose and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by Systemic IV Administration of Escalating Doses of [177Lu]DOTA-biotin in Patients With Solid Tumors or Lymphomas With Injectable Neoplastic Lesions.

Local treatment of unresectable tumors is challenging, particularly with radioactivity. Current practice relies on external beam irradiation or on a variety of medical devices for brachytherapy. Both approaches proved useful in controlling tumor growth but are characterized by poor patient's compliance, significant side effects, high costs and technological complexity hampering wide-spread use. The use of AvidinOX for radionuclide therapy of inoperable cancer lesions will offer a number of advantages compared to current brachytherapy. In fact, the perfusion of a target tissue with AvidinOX, compared to current devices, will allow adapting the therapy to the tumor/organ shape, and it will also make it possible to delay the administration of radioactivity for several days which, according to pre-clinical studies, might be also divided up into repeated doses. AvidinOX linking stably to tissue proteins, does not exhibit the problem of seed migration which is associated with high morbidity. Based on previous findings with AvidinOX in combination with radionuclides in pre-clinical studies as well as data from the clinical use in liver metastases, it can be assumed that intralesional injections of AvidinOX followed by intravenous injections of 177Lu-ST2210 could be a safe and efficacious method for treating inoperable tumor lesions.

Start Date07 Aug 2017

Sponsor / Collaborator

Alfasigma SpA

NCT02053324 / TerminatedPhase 1

A Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, Dosimetry, Maximum Tolerated Dose and Preliminary Efficacy of Intra-lesionally Injected AvidinOX, Followed by Systemic IV Administration of Escalating Doses of [177Lu]DOTA-biotin in Patients With Liver Metastases From Colorectal Cancer

The purpose of the study is to assess a new treatment for patients with liver tumor metastases from colorectal cancer. The treatment has never been used in humans before. The treatment foresees the use of two compounds: AvdinOX and [177Lu]DOTA-biotin.
AvidinOX is a new compound, essentially a natural protein obtained from hen eggs, while [177Lu]DOTA-biotin is a new chemical compound resulting from the combination of the DOTA-biotin (also deriving from a natural vitamin which is biotin) with the 177Lutetium, an atom which emits radiation.
AvidinOX will be injected directly into the metastases in the liver and [177Lu]DOTA-biotin will be injected into the arm vein.
One specific property of AvidinOX is that it chemically links to the tumor tissues when it is injected while maintaining the capacity to take up [177Lu]DOTA-biotin. Once locally bound in tumor tissue, AvidinOX becomes an "artificial receptor" for intravenously injected [177Lu]DOTA-biotin, which allows an internal radiation therapy of the tumor tissue.
The treatment of liver metastases with local injection of AvidinOX and the following intra-venous injection of [177Lu]DOTA-biotin could be simpler and more tolerable than the current available treatments.

Start Date11 Nov 2013

Sponsor / Collaborator

Alfasigma SpA

100 Clinical Results associated with AvidinOx-Lu-177-DOTA-Biotin

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100 Translational Medicine associated with AvidinOx-Lu-177-DOTA-Biotin

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100 Patents (Medical) associated with AvidinOx-Lu-177-DOTA-Biotin

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22

Literatures (Medical) associated with AvidinOx-Lu-177-DOTA-Biotin

30 Dec 2021·Urologiia

The use of rectal suppositories with oxidised dextran for calculous prostatitis

Article

Author: Novikova, E G ; Troitsky, A V ; Ukah, H U

This article presents its own experience of using suppositories with oxidised dextran in the treatment of a patient with recurrent bacterial prostatitis complicated by prostate calcifications, these are the positive effects on the use of suppositories with oxidised dextran: a decrease in the size of calcified areas, a stable elimination of opportunistic microflora and the achievement of long-term remission of the disease.

01 Oct 2021·European Journal of Nuclear Medicine and Molecular ImagingQ1 · MEDICINE

Preclinical evaluation of [225Ac]Ac-DOTA-TATE for treatment of lung neuroendocrine neoplasms

Q1 · MEDICINE

Article

Author: Wadas, Thaddeus J ; Strosberg, Jonathan R ; Wang, Zhen ; El-Haddad, Ghassan ; Engelman, Robert W ; Pandya, Darpan N ; Morse, David L ; Reff, Jordan N ; Tafreshi, Narges K ; Ji, Haitao ; Budzevich, Mikalai M ; Tichacek, Christopher J ; Boulware, David C ; Chiappori, Alberto A

PURPOSEThere is significant interest in the development of targeted alpha-particle therapies (TATs) for treatment of solid tumors. The metal chelator-peptide conjugate, DOTA-TATE, loaded with the β-particle emitting radionuclide ¹⁷⁷Lu ([¹⁷⁷Lu]Lu-DOTA-TATE) is now standard care for neuroendocrine tumors that express the somatostatin receptor 2 (SSTR2) target. A recent clinical study demonstrated efficacy of the corresponding [²²⁵Ac]Ac-DOTA-TATE in patients that were refractory to [¹⁷⁷Lu]Lu-DOTA-TATE. Herein, we report the radiosynthesis, toxicity, biodistribution (BD), radiation dosimetry (RD), and efficacy of [²²⁵Ac]Ac-DOTA-TATE in small animal models of lung neuroendocrine neoplasms (NENs).METHODS[²²⁵Ac]Ac-DOTA-TATE was synthesized and characterized for radiochemical yield, purity and stability. Non-tumor-bearing BALB/c mice were tested for toxicity and BD. Efficacy was determined by single intravenous injection of [²²⁵Ac]Ac-DOTA-TATE into SCID mice-bearing human SSTR2 positive H727 and H69 lung NENs. RD was calculated using the BD data.RESULTS[²²⁵Ac]Ac-DOTA-TATE was synthesized with 98% yield, 99.8% purity, and displayed 97% stability after 2 days incubation in human serum at 37 °C. All animals in the toxicity study appeared healthy 5 months post injection with no indications of toxicity, except that animals that received ≥111 kBq of [²²⁵Ac]Ac-DOTA-TATE had chronic progressive nephropathy. BD studies revealed that the primary route of elimination is by the renal route. RD calculations determined pharmacokinetics parameters and absorbed α-emission dosages from ²²⁵Ac and its daughters. For both tumor models, a significant tumor growth delay and time to experimental endpoint were observed following a single administration of [²²⁵Ac]Ac-DOTA-TATE relative to controls.CONCLUSIONSThese results suggest significant potential for the clinical translation of [²²⁵Ac]Ac-DOTA-TATE for lung NENs.

01 Nov 2018·Bioorganic & Medicinal Chemistry LettersQ4 · MEDICINE

Growth inhibition of human ovarian carcinoma by a novel AvidinOX-anchored biotinylated camptothecin derivative

Q4 · MEDICINE

Article

Author: Dallavalle, Sabrina ; Minenkova, Olga ; Vesci, Loredana ; Santapaola, Daniela ; Musso, Loana ; Cincinelli, Raffaella ; De Santis, Rita ; Giannini, Giuseppe

Oxidized form of avidin, named AvidinOX, provides stable fixation of biotinylated molecules in tissues thus representing a breakthrough in topical treatment of cancer. AvidinOX proved to be a stable receptor for radiolabeled biotin, biotinylated antibodies and cells. In order to expand applicability of the AvidinOX-based delivery platform, in the present study we investigated the possibility to hold biotinylated chemotherapeutics in AvidinOX-treated sites. A novel biotinylated gimatecan-derived camptothecin, coded ST8161AA1, was injected at suboptimal doses into human tumors xenografted in mice alone or pre-complexed to AvidinOX. Significantly higher growth inhibition was observed when the drug was anchored to AvidinOX suggesting the potential utility of this delivery modality for the local treatment of inoperable tumors.

100 Deals associated with AvidinOx-Lu-177-DOTA-Biotin

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Colorectal Cancer	Phase 1	-	Sigma-Tau BV	-
Lymphoma	Phase 1	-	Sigma-Tau BV	-
Malignant ascites	Preclinical	IT	Sigma-Tau Industrie Farmaceutiche Riunite SpA	-
Malignant ascites	Preclinical	CH	Sigma-Tau Industrie Farmaceutiche Riunite SpA	-
Malignant ascites	Preclinical	AT	Sigma-Tau Industrie Farmaceutiche Riunite SpA	-
Colorectal Liver Metastases	Discovery	AT	Alfasigma SpA	11 Nov 2013
Colorectal Liver Metastases	Discovery	IT	Alfasigma SpA	11 Nov 2013
Liver Cancer	Discovery	AT	Alfasigma SpA	11 Nov 2013
Liver metastases	Discovery	IT	Alfasigma SpA	11 Nov 2013
Liver metastases	Discovery	AT	Alfasigma SpA	11 Nov 2013