• All study objectives were met, demonstrating safety across dose groups and confirming efficacy and durability at the selected doses against placebo (lidocaine) and active control (steroid).

• All RTX doses (7.5 to 20 μg) were well-tolerated, with few severe or serious adverse events (AEs). The majority of reported AEs related to pain post-administration and resolved within hours following treatment. Very few severe AEs were reported across groups (including placebo) with no dose correlation. RTX post-injection administration pain was easily controlled.

• RTX 20mcg dose outperformed all other dose groups (including the approved drug for this indication (intra-articular corticosteroids)) for efficacy and durability at and beyond 26 weeks post-treatment. RTX 20mcg and 12.5mcg have been selected as the clinically optimal and minimally effective doses for further phase 2 pivotal or phase 3 trials.
  

SAN DIEGO, Sept.  07, 2023  (GLOBE NEWSWIRE) -- Sorrento Therapeutics, Inc. (OTC: SRNEQ, "Sorrento") announced today positive Phase 2a top-line clinical trial results for the RTX program.

The Phase 2a study follows the positive observations from the Phase 1b/2 trial results (NCT03542838) of RTX Day 84 patient data, for which Sorrento has completed the one-year follow up for the last patient dosed in February 2021.

The phase 2 trial, a multi-center, double blind, placebo- and active-controlled study, assessed the efficacy and safety of several dose groups of RTX to manage pain in patients with moderate-to-severe OAK (clinicaltrials.gov: NCT04885972). Given the durability of OAK pain relief response to RTX demonstrated in earlier phase 1b/2 trials, Sorrento decided to include an active approved comparator (Zilretta intra-articular corticosteroids) in the current trial protocol.

Top-Line Safety Outcomes (Summary)

Generally, treatment was well-tolerated, with the most common noted AE being pain following topical capsaicin 0.1% given to all patients for blinding purposes and study drug administration in the knee (across all dose groups).

Very few serious AEs were noted across all dose groups, with one in particular (see below for additional detail) in the 15mcg RTX group being severe/life threatening (hypertension following drug administration), which resolved within hours with treatment of pain and no additional intervention.

In the cases requiring pain control (any group) the dose of opioid was comparable. A few subjects in RTX groups required use of low dose oral opioids for up to 6 hours in some cases of prolonged moderate discomfort/pain. No patient required additional pain control or intervention after 6 hours or in the days following the day of administration and no patient left the clinic with opioids or an opioid prescription.

A table accompanying this announcement is available at

Subject 008-005, a 55-year-old female with a prior history of hypertension (HTN) and morbid obesity (BMI 46.9) developed elevated blood pressure about fourteen minutes post-RTX dose (208/147), which coincided with severe pain. The subject received hydromorphone 0.8 and 0.4 mg IV and then oxycodone 5 mg twice, and the HTN resolved without any other intervention. The HTN did not recur, and the subject's ECG was normal. Discharge blood pressure was 140/74. Sponsor's medical monitor disagreed with the characterization as life-threatening or an SAE as the clinic stay was not prolonged and the HTN required no treatment other than treating the subject's pain. Sponsor also felt that the AE should have been considered a related event (marked unrelated by investigator).

Top Line Efficacy and Durability Outcomes (Summary)

The RTX 20mcg dose group performed best among all dose groups, including placebo (lidocaine only) and approved intra-articular corticosteroid (Zilretta) on short-term and prolonged pain relief measures (SPID, KOOS, WOMAC).

Summary of Pain Intensity Difference (SPID)

Although at many time points, RTX 20mcg was statistically significant as compared to the approved drug (Zilretta) in this indication active control, we note that the study was not powered to demonstrate statistical significance for all end points listed (primary, secondary), with only 120 patients enrolled across 5 RTX dose groups and early terminations due to the Company's previously announced bankruptcy proceedings.

Despite the limitations of the study (small number of patients per group, high variability of placebo responders due to intra-articular use of 10ml lidocaine and capsaicin cream for blinding per FDA request), the results = demonstrate that RTX 20mcg is an effective pain treatment for longer durations (up to one year), with better score improvements at week 26 and 52 than the current standard of care (active steroid injection. Zilretta) up to and past week 26.

A higher proportion of patients responded to treatment with RTX 20mcg than any other treatment group, including Zilretta. Reduction in pain was also more pronounced with RTX 20mcg than with any other treatment group, including placebo and active control.

A table accompanying this announcement is available at

Durability of treatment was nearly twice as long for RTX 20mcg than active steroid control (mean time to return to 10% of baseline of 19 weeks for RTX versus 10 weeks for Zilretta).

In conclusion, we report that the phase 2a OAK study for RTX has met all the primary and secondary objectives for the study. The Phase 2a results were consistent with the prior safety profile of the drug from the previously completed Phase 1 study and has allowed for the potential determination of a therapeutically effective dose for further phase 2 pivotal or phase 3 studies, which is expected to be powered with a sufficient number of patients to provide significantly different results from the controls.

"We are extremely pleased with the outcome of this study. The clinical trial confirmed the potential of resiniferatoxin (RTX) in helping patients with moderate to severe osteoarthritis pain for at least 6 months, if not longer. No other drug on the market can provide this much pain relief, for this long a period, from a single administration," stated Dr. Henry Ji, Chairman and Chief Executive Officer.

About RTX

A thousand times "hotter" than pure capsaicin (16 billion Scoville units versus 16 million), and with a high affinity for afferent sensory pain nerves, RTX binds to TRPV1 receptors present and selectively ablates the nerve endings responsible for pain signals experienced by patients1. Delivered peripherally (into the joint space) the transient nerve ending ablation effect can have profound clinical benefits lasting for months to years (as shown in canine studies2).

The first arthritis pain clinical trial in humans was completed in 2021. That study was a multicenter, placebo-controlled Phase 1b/2 study to assess the safety and define the maximally tolerated dose of RTX administered in the knee joint in patients with moderate to severe pain associated with osteoarthritis of the knee. The study was a dose-escalation trial in which cohorts of patients receive increasing doses of RTX until the maximum tolerated dose (MTD) was achieved. The primary objective of the study was to evaluate the safety of RTX and identify the recommended Phase 3 dose. The secondary objective was to assess the preliminary efficacy of RTX measured by assessing changes in the intensity of pain using the A1 score from the WOMAC, a widely used proprietary validated pain questionnaire.

The second arthritis pain phase 2a clinical trial in humans completed enrollment in September 2022. The results of study are expected to confirm the phase 3 doses and demonstrate long-term effectiveness of RTX in controlling osteoarthritis pain when compared to placebo or active steroid intra-articular injections.

Sorrento continues to progress as planned on all clinical fronts of the RTX program, including exploring additional orphan indications with breakthrough potential.

RTX is an extremely potent compound used therapeutically in very small concentrations. It is very challenging to formulate and keep stable long-term when made in large quantities. Sorrento has been working on process optimization of RTX manufacturing for several years and continues to advance the validation and scale up, with the expectation to have final validated batches completed by the end of 2023. Ensuring the company can meet market demands from API to finished product once phase 3 trials have been completed has been identified as a critical priority, which Sorrento is currently addressing.

The osteoarthritis treatment market and in particular the Knee Osteoarthritis and injectable markets have historically seen healthy growth and are expected to continue the trend as populations age and present excessive weight.

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 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 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.