Sorrento Releases Positive Results from a Phase 1b Study in China in COVID-19 Patients and is Ready for Pivotal Phase 3 trials with OVYDSO™ (STI-1558), an Oral Mpro Inhibitor as a Standalone Treatment for COVID-19 without the Need for Ritonavir Boosting
Topline safety, antiviral effectiveness and pharmacokinetic (PK) data from a Phase 1b Study in China are released from the single ascending dose (SAD) portion of the study with the doses from 300 mg to 2,000 mg in 32 healthy volunteers and the multiple ascending dose (MAD) portion of the study in 46 COVID-19 patients with 300 mg BID, 600 mg BID and 800 mg BID daily dosing for 7.5 days.
Overall, STI-1558 was well-tolerated at all doses tested, with most subjects in both the SAD and MAD portions of the study reporting no adverse events (AEs). There was no dose limiting toxicity during the study. There were no severe or serious AEs, no premature discontinuations of STI-1558 due to an AE, and no deaths. Most AEs were mild, unrelated and required no medical treatment.
In the MAD portion of the study (n=41 evaluable), COVID-19 patients (n=29) treated with STI-1558 compared to placebo (n=12) were found to have significant viral RNA load reductions on Days 2, 4 and 6 post treatment. At the recommended dose of 600 mg BID, a significant viral load reduction was seen on Day 2 post-treatment (1.5 log lower than placebo, p=0.036), which indicates strong and early antiviral activity of STI-1558 in COVID-19 patients.
The Pharmacokinetics (PK) profile in this trial was very similar to the profile seen in the completed Australian Phase 1 trial, potentially indicating that there are no ethnic differences in STI-1558 PK. In the China MAD portion of the study, the PK profile in patients was also similar to the healthy volunteers in the Australian Phase 1 trial, with the trough concentrations (Ctrough) 265 (300 mg BID), 431 (600 mg BID) and 518 (800 mg BID) ng/mL values significantly higher than the EC90 value in the cellular antiviral assays. These data further confirm that adequate blood levels are achieved in COVID-19 patients without the need for Ritonavir, a CYP3A4 potent inhibitor, as a booster.
After communication with the Chinese authorities, a Phase 3 protocol in 1200 COVID-19 patients has been submitted to the National Medical Products Administration of China (NMPA). The Phase 3 trial will be commenced soon in China together with a planned U.S. Phase 2 trial and a planned Mexico Phase 2/3 trial.
SAN DIEGO, Jan. 09, 2023 (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (Nasdaq: SRNE, “Sorrento”) today released unblinded Phase 1b study data of its oral main viral protease (Mpro) inhibitor, OVYDSO™ (STI-1558) in COVID patients.
This Phase 1b safety, PK and efficacy study in healthy volunteers and COVID patients was conducted in China. The study (MPR-COV-101CN) is entitled: “A Randomized, Double-Blind, Placebo-Controlled, Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Single and Multiple Oral Doses of STI-1558 in Healthy Volunteers and COVID Patients”. In the SAD portion of the study, four dose-escalation cohorts (single oral dose of 300, 600, 1200, and 2000 mg STI-1558 or placebo) were conducted with eight subjects in each cohort – randomized 3:1. In the MAD portion of the study, three dose-escalation cohorts with daily dose of 300 mg BID, 600 mg BID or 800 mg BID for consecutive 7.5 days (total 15 doses) were conducted with eight participants infected with SARS-CoV-2 in each dose cohort – randomized 3:1 (active:placebo), and in the 600 mg BID dose cohort, an additional 16 participants infected with SARS-CoV-2 (10:6, active:placebo) were added as a cohort extension.
The topline safety, PK and efficacy data from the SAD and MAD portions of the study are now available. Overall, STI-1558 was well-tolerated at these doses, with most subjects in both the SAD and MAD portions of the study reporting no AEs. There was no dose limiting toxicity during the study. There were no severe or serious AEs, no premature discontinuations of STI-1558 due to an AE, and no deaths. Most AEs were mild, transient, unrelated and required no medical treatment.
A total of 12 subjects reported an AE in the SAD portion of the study, with one AE of elevated blood thyroid-stimulating hormone (TSH) deemed related to STI-1558 in the 2000 mg cohort. No headaches were seen in this study. In the MAD portion of the study in COVID-19 patients, 20 subjects from a total of 46 subjects reported AEs, with only four subjects experiencing STI-1558-related events. These four AEs included two subjects with mild or moderate liver enzyme elevation (ALT/AST) without bilirubin elevation in the 300 BID and 800 BID cohorts, one subject with mild hyperuricemia in the 600 mg BID cohort and one subject with mild rash in the 800 mg BID cohort.
Antiviral activity was evaluated in the MAD portion of the study in participants infected with SARS-CoV2 (300 mg BID, 600 mg BID and 800 mg BID daily for 7.5 days). The viral RNA load in participants infected with SARS-CoV2 was measured by quantitative PCR. The viral RNA load (log10 copies/ml) was significantly reduced in COVID-19 patients (n=29) treated with STI-1558 on Days 2, 4 and 6 post-treatment in comparison with placebo, indicating the strong antiviral activity of STI-1558 in COVID-19 patients. Notably the significant reduction of viral RNA (Log10 copies/ml) can be seen as early as day 2 after being treated with STI-1558 at the likely therapeutic dose of 600 mg BID (1.5 log lower than placebo, p=0.036). These data demonstrate early antiviral activity of STI-1558 in COVID-19 patients.
The PK profiles in the China trial were similar to the Australian trial and the linear and semi-log PK plots for doses of 300 mg, 600 mg, 1200 mg and 2000 mg are proportional in the SAD portion of study in healthy volunteers with AUC of 11.4 h* µg/mL, 24.0 h* µg /mL, 60.1 h* µg /mL and 84.4 h* µg /mL, respectively, and the T1/2 is from 21.4 h to 24.5 h. In the MAD portion of the study in COVID-19 patients, after 7.5 days of treatment (total of 15 doses), no accumulation was seen in all three MAD dose cohorts. The trough concentrations (Ctrough) in 300 mg BID, 600 mg BID and 800 mg BID cohorts were 265 ng/mL, 431 ng/mL and 518 ng/mL, respectively, similar to the trough concentrations in the Australian trial in healthy volunteers (190 ng/mL, 354 ng/mL and 418 ng/mL). These Ctrough values are significantly above the EC90 value for viral inhibition in preclinical models.
Based on the safety and PK profiles and significant antiviral efficacy in COVID-19 patients, a 600 mg twice-daily dose for 5 days has been selected as a recommended dose for Phase 3 studies for the standalone treatment of COVID-19.
After communication with the regulatory agency, a Phase 3 protocol was submitted to China NMPA. The Phase 3 trial (MPR-COV-301CN) is entitled: “A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess the Efficacy and Safety of STI-1558 for Treatment of Mild and Moderate Symptomatic Adults Infected with SARS-CoV-2”. Once cleared by NMPA, the study, which plans to enroll 1200 COVID-19 patients, will be subsequently commenced.
“We are excited to see the similarities of PK in the China study and the Australian study. The significant antiviral effectiveness and tolerability of OVYDSO in COVID patients suggests this compound will significantly benefit patients and will require no boosting with Ritonavir. We expect to initiate the Phase 3 trial very soon in China, and meanwhile we are engaging with regulatory agencies on a global Phase 2/3 trial design in order to initiate OVYDSO Phase 2/3 trials in Mexico and the U.S. as soon as possible,” stated Henry Ji, Ph.D., Chairman and CEO of Sorrento.
About Sorrento Therapeutics, Inc.
Sorrento is a clinical and commercial stage biopharmaceutical company developing new therapies to treat cancer, pain (non-opioid treatments), autoimmune disease and COVID-19. Sorrento's multimodal, multipronged approach to fighting cancer is made possible by its extensive immuno-oncology platforms, including key assets such as Abivertinib, next-generation tyrosine kinase inhibitors (“TKIs”), fully human antibodies (“G-MAB™ library”), immuno-cellular therapies (“DAR-T™”), antibody-drug conjugates (“ADCs”), and oncolytic virus (“Seprehvec™”). Sorrento is also developing potential antiviral therapies and vaccines against coronaviruses, including STI-1558, COVISHIELD™ and COVIDROPS™, COVI-MSC™; and diagnostic test solutions, including COVIMARK™.
Sorrento's commitment to life-enhancing therapies for patients is also demonstrated by our effort to advance a TRPV1 agonist, non-opioid pain management small molecule, resiniferatoxin (“RTX”), and SP-102 (10 mg, dexamethasone sodium phosphate viscous gel) (SEMDEXA™), a novel, viscous gel formulation of a widely used corticosteroid for epidural injections to treat lumbosacral radicular pain, or sciatica, and to commercialize ZTlido® (lidocaine topical system) 1.8% for the treatment of postherpetic neuralgia (PHN). RTX has been cleared for a Phase II trial for intractable pain associated with cancer and a Phase II trial in osteoarthritis patients. Positive final results from the Phase III Pivotal Trial C.L.E.A.R. Program for SEMDEXA™, its novel, non-opioid product for the treatment of lumbosacral radicular pain (sciatica), were announced in March 2022. ZTlido® was approved by the FDA on February 28, 2018.
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This press release and any statements made for and during any presentation or meeting contain forward-looking statements related to Sorrento Therapeutics, Inc., under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995 and subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include statements regarding STI-1558, including the recommended dose for Phase 2/3 trials, the potential appropriateness of STI-1558 as a standalone treatment for COVID-19, the potential initiation of the STI-1558 Phase 2/3 trials in Mexico, the U.S. and China, the global Phase 2/3 trial design, and the expected timing, number of patients to be enrolled and other enrollment plans with respect to any Phase 2 or 3 trials for STI-1558. Sorrento’s products, technologies and prospects. Risks and uncertainties that could cause our actual results to differ materially and adversely from those expressed in our forward-looking statements, include, but are not limited to: risks related to Sorrento's technologies and prospects, including, but not limited to risks related to safety and efficacy of STI-1558 and seeking regulatory approval for STI-1558; clinical development risks, including risks in the progress, timing, cost, and results of clinical trials and product development programs; risk of difficulties or delays in obtaining regulatory approvals; risks that clinical study results may not meet any or all endpoints of a clinical study and that any data generated from such studies may not support a regulatory submission or approval; risks that prior test, study and trial results, including those for STI-1558, may not be replicated in continuing or future studies and trials; risks of manufacturing and supplying drug product; risks related to leveraging the expertise of its employees, subsidiaries, affiliates and partners to assist Sorrento in the execution of its product candidates’ strategies; risks related to the global impact of COVID-19; and other risks that are described in Sorrento's most recent periodic reports filed with the Securities and Exchange Commission, including Sorrento's Annual Report on Form 10-K for the year ended December 31, 2021 and subsequent Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission, including the risk factors set forth in those filings. Investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this release, and we undertake no obligation to update any forward-looking statement in this press release except as required by law.
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