FDA Grants Orphan Drug Designation to Veyonda for Soft Tissue Sarcoma


The FDA has granted an orphan drug designation to Veyonda, a novel proprietary formulation of idronoxil, for use as a potential therapeutic option in patients with soft tissue sarcoma.



The FDA has granted an orphan drug designation to Veyonda, a novel proprietary formulation of idronoxil, for use as a potential therapeutic option in patients with soft tissue sarcoma.1

The active ingredient in the agent is idronoxil, which is a first-in-class, dual-acting oncotoxic and immuno-oncology molecule that has been shown to have unique anti-inflammatory properties, according to Noxopharm Limited, the drug developer.2

Veyonda has been shown to be able to directly kill cancer cells and to work in tandem with the immune system to eliminate tumors. Idronoxil is known to block the production of inflammatory cytokines that can cause extreme inflammatory response and the development of septic shock. The product is under evaluation for use with radiation, immunotherapy, and chemotherapy in several cancers.

“The orphan drug designation will significantly increase the value proposition of Veyonda to potential purchasers or licensees by both lowering current development costs and by providing future competitive and financial advantages as Veyonda progresses through the clinical trial stages toward registration and approval for sale in the United States,” Gisela Mautner, MD, PhD, MPH, MBA, FACPE, chief executive officer of Noxopharm Limited, stated in a press release. “With the FDA orphan drug designation now secured for Veyonda, the Noxopharm team is excited to move our preclinical assets along the drug development process, while continuing to deliver on our clinical program plan.”

Veyonda is under investigation in combination with doxorubicin as a first-line treatment in patients with metastatic soft tissue sarcoma, as part of the open-label, dose-escalation and -expansion, phase 1 CEP-2 trial, which is anticipated to enroll approximately 30 patients.

The study was given the green light from the FDA under the investigational new drug process based upon evidence that the agent may improve upon generally poor responses achieved with chemotherapy in those with sarcoma.3 The trial builds upon the positive findings yielded from the multicenter, phase 1 CEP-1 trial, which had delivered the proof-of-concept of Veyonda in combination with chemotherapy.

The open-label, nonrandomized, 2-dose cohort trial examined Veyonda as a single agent (phase 1a) and in combination with carboplatin (phase 1b) in patients with solid tumors such as prostate cancer, breast cancer, ovarian cancer, lung cancer, or head and neck cancer, who had stopped responding to standard therapeutic options.

To be eligible for inclusion, patients needed to have histologically confirmed locally advanced or metastatic disease, at least 1 measurable lesion, an ECOG performance status of 0 or 1, a life expectancy of 12 weeks or more, and acceptable hematologic, hepatic, and renal function.

If patients had cancers involving the central nervous system, clinically significant, uncontrolled cardiac disease or myocardial infarction within the past year, uncontrolled infection or systemic disease, or any major surgery, radiotherapy, or immunotherapy within the past 21 days, they were excluded. Patients also could not have a history of solid organ transplant.

Participants were divided into 2 dosing cohorts: 400 mg and 800 mg. These doses were chosen based on the OVATURE trial, in which 1200 mg of oral idronoxil was utilized in combination with carboplatin. No dose modifications of the agent were made on the basis of weight except for those who exceeded 100 kg; for those patients, the dose could be increased per investigator discretion.

In the phase 1a monotherapy study, cohort 1 was administered 400 mg daily, whereas cohort 2 received 800 mg daily, for 14 consecutive days; this was followed by 1 week of rest, comprising a 21-day cycle. All of those who completed the monotherapy treatment without experiencing significant adverse effects (AEs) were eligible to participate in the phase 1b study. Here, patients were given the agent in combination with carboplatin for up to six 28-day treatment cycles at dosages that were determined to be acceptable per investigator decision.

Cohorts 1 and 2 continued to receive the agent at 400 mg or 800 mg during this phase of the trial. The agent was administered rectally for the first week of each treatment cycle. Intravenous carboplatin was given on day 2 of each cycle at 600 mg for cycles 1b through 3b and at 900 mg for cycles 4b through 6b.

A total of 20 patients underwent screening; 8 of these patients comprised cohort 1 and 11 patients made up cohort 2. Only 5 patients in cohort 1 and 9 patients in cohort 2 were included in the efficacy analysis for the trial. All patients in both cohorts completed the monotherapy phase, although 3 were determined to be nonevaluable and were replaced by 3 patients who entered the second phase in accordance with trial protocol.

Patient characteristics in the cohorts were noted to be comparable with regard to age, height, weight, and gender. All participants were White. Moreover, 33.3% of patients had breast cancer, 27.8% had lung cancer, 16.7% had ovarian cancer, and 16.7% had prostate cancer, which was noted to be equally distributed between the cohorts. Prior treatment with hormone therapy or surgery was common in this population.

Although the study was not powered to measure efficacy, the sum of target lesion diameters showed that more patients experienced reductions from day 1 of cycle 3b to day 1 of cycle 6b than increases. Most participants achieved disease stability throughout treatment. Notably, by cycle 6b, 63.3% of the 5 patients had stable disease or achieved a partial response.

All of those in cohort 1 were included in the safety analysis. Ten of the 11 patients in cohort 2 were included, as 1 patient withdrew consent prior to their first dose of study treatment. Data showed that at least 1 treatment-emergent AE occurred in 77.8% of patients, the most common of which being blood and lymphatic system disorders (44.4%), gastrointestinal disorders (16.7%), metabolism and nutrition disorders (16.7%), as well as respiratory, thoracic and mediastinal disorders (16.7%).

A total of 5 patients from the cohort receiving 400 mg of the agent withdrew from the study. One did so due to death, 2 because of progressive disease, and 2 for other unspecified reasons. Four patients from the cohort receiving 800 mg of the agent withdrew from the trial; 2 did so because of death, 1 because of toxicity, and 1 due to withdrawn consent.

Twenty-two percent of patients in the combination phase of the trial experienced serious toxicities that resulted in premature withdrawal from the trial; 3 of these patients were in cohort 2. Three of these effects resulted in death (1 in cohort 1 and 2 in cohort 2). However, none of these deaths were determined to be associated with the study drug per investigator assessment.


  1. Orphan drug designation granted to Noxopharm by US FDA. News release. Noxopharm Limited; March 22, 2022. Accessed March 29, 2022. https://bit.ly/3NHQMWr
  2. Our science: about Veyonda. Noxopharm Limited website. Accessed March 29, 2022. https://bit.ly/3NvO31R
  3. Our programs: CEP program. Noxopharm Limited website. Accessed March 29, 2022. https://bit.ly/3iNGZzy
  4. Kiknavelidze K, Shavdia M, Chikhladze N, et al. NOX66 monotherapy, and in combination with carboplatin, in patients with refractory solid tumors: phase Ia/b study. Curr Ther Res Clin Exp. Published online March 28, 2021. doi:10.1016/j.curtheres.2021.100631
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