FDA Grants Orphan Drug Designation to Veyonda for Patients With Soft Tissue Sarcoma


Orphan drug designation has been granted to Veyonda as a form of treatment in patients with soft tissue sarcoma.

The FDA has granted an orphan drug designation to Veyonda, a novel proprietary formulation of idronoxil, as a form of treatment in patients with soft tissue sarcoma.1

Veyonda is a first-in-class, dual-acting oncotoxic and immuno-oncology molecule, which has shown unique anti-inflammatory properties and demonstrated 2 actions including being able to kill cancer cells directly and working along with the body’s immune system to destroy tumors.2

The active ingredient in Veyonda is the small molecule, idronoxil, which is currently under investigation for improving the effectiveness of immunotherapy, chemotherapy and radiation therapy treatment for a number of cancers. Idronoxil has demonstrated being able to block the production of inflammatory cytokines which cause extreme inflammatory response and the development of septic shock.

“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.”

An ongoing phase 1 trial, CEP-2, is currently examining Veyonda in combination with doxorubicin as a first-line treatment option for patients with metastatic soft tissue sarcoma.3 Approximately 30 patients are expected to be recruited into the open-label, dose-escalation and -expansion for whom no remaining standard treatment options are available.

The FDA gave the study the approval to proceed under the investigational new drug process after evidence showed that the agent may improve upon generally poor responses achieved with chemotherapy in patients with sarcoma.3The trial follows the multicenter, phase 1 CEP-1 trial, and builds on the positive findings which had delivered the proof-of-concept of Veyonda in combination with chemotherapy.

CEP-1 examined Veyonda as a single agent in phase 1a in addition to it in combination with carboplatin in phase 1b.4 This trial focused on patients with solid tumors including prostate cancer, breast cancer, ovarian cancer, lung cancer, or head and neck cancer, who had stopped responding to standard therapeutic options.

Eligibility was open to patients with progressive disease and were assessed as having limited survival prospects. Additionally, 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.

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

Participants were divided into 1 of 2 cohorts. In the phase 1a monotherapy study, cohort 1 was administered 400 mg daily, and cohort 2 was given 800 mg daily. This continued for 14 consecutive days and was followed by 1 week of rest, comprising a 21-day cycle.

Patients who completed the monotherapy treatment without experiencing significant adverse effects (AEs) were eligible to participate in the phase 1b study where they received the agent in combination with carboplatin for up to 6 28-day treatment cycles at dosages determined to be acceptable per investigator decision.

During this phase of the trial, both cohorts continued to receive the agent at 400 mg or 800 mg. The agent was administered rectally during week 1 of each treatment cycle while 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 with 8 in cohort 1 and 11 patients in 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, but 3 were determined to be non-evaluable and replaced by 3 patients who entered phase 2 in accordance with trial protocol.

Cohort 1 included all of its patients in the safety analysis while 10 of the 11 patients in cohort 2 were included due to 1 patient withdrawing consent prior to their first dose of study treatment.

Findings revealed at least 1 treatment-emergent AE to occur 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 withdrawal was due to death, 2 due to progressive disease, and 2 for other unspecified reasons. Four patients from the cohort receiving 800 mg of the agent withdrew from the trial; 2 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.

Overall, the favorable safety profile demonstrated in the trial justifies the continuation of clinical research with CEP-2.

  1. Orphan drug designation granted to Noxopharm by US FDA. News release. Noxopharm Limited; March 22, 2022. Accessed March 30, 2022. https://bit.ly/3NHQMWr
  2. Our science: about Veyonda. Noxopharm Limited website. Accessed March 30, 2022. https://bit.ly/3NvO31R
  3. Our programs: CEP program. Noxopharm Limited website. Accessed March 30, 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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