South Rampart Pharma Receives U.S. FDA Fast Track Designation for SRP-001 for Acute Pain

On October 12, 2023, South Rampart Pharma, Inc. announced that the U.S. Food and Drug Administration (FDA) had granted Fast Track status to its drug candidate, SRP-001, intended for the management of acute pain. SRP-001 is an innovative, pioneering non-opioid analgesic that activates pain signaling pathways in the periaqueductal grey (PAG) region of the midbrain, free from liver and kidney toxicity concerns. 

SRP-001 exerts its influence on pain-related genes by modulating pathways within the PAG region, including the endocannabinoid, mechanical nociception, and fatty acid amide hydrolase pathways. Notably, SRP-001 distinguishes itself from opioids as it lacks the potential for abuse and addiction. Furthermore, it stands apart from acetaminophen due to its absence of hepatotoxicity concerns, as it neither generates the harmful metabolite NAPQI nor disrupts liver cell tight junctions. In comparison to acetaminophen, SRP-001 showcases similar analgesic properties without the risk of liver harm, and it doesn’t carry the kidney toxicity risk associated with NSAIDs. 

In preclinical pain models, including inflammatory von Frey, visceral, and somatic pain models, SRP-001 consistently demonstrates efficacy. Interim findings from the Phase 1 trial (NCT05484414) confirm SRP-001’s safety, tolerability, and robust pharmacokinetics. SRP-001 represents a promising alternative to existing pain medications like opioids, acetaminophen, and NSAIDs, potentially offering a safer and more effective option for pain management.

“Despite the ongoing opioid crisis and limitations of existing pain medications, including acetaminophen as the leading cause of acute liver failure in the U.S. and other parts of the Western world, innovation in the pain space remains surprisingly stagnant,” said Hernan Bazan, MD, CEO & Co-Founder of South Rampart Pharma. “Today’s acknowledgment by the FDA of the critical need for innovative medications in acute pain perfectly matches our unwavering commitment to expedite its clinical development and bring this potentially transformative therapy to market as swiftly as possible.”

“In the CNS and pain space, Fast Track designation for SRP-001 isn’t just a regulatory milestone; it’s a commercial accelerant. This designation recognizes the scientific innovation behind SRP-001 and potential market impact as a safer, more effective alternative to opioids and acetaminophen,” Neil Singla, MD, Chief Scientific Officer at Lotus Clinical Research.

In August 2023, South Rampart made an announcement regarding the initiation of its Phase 1 trial (NCT05484414), a study involving multiple ascending doses (MAD). The primary goal of this MAD study is to evaluate the safety, tolerability, as well as the pharmacokinetics/pharmacodynamics (PK/PD) of oral SRP-001 in healthy male and female volunteers. The primary endpoints for assessment are safety and tolerability, involving the evaluation of adverse events (AEs), vital signs, electrocardiograms (ECGs), physical examinations, laboratory safety tests, and specific PK/PD parameters. The trial is anticipated to conclude in the fourth quarter of 2023.

Acute pain presents a substantial healthcare burden, impacting individuals’ quality of life and straining healthcare resources. As per the DelveInsight estimates, there were approximately 100 million cases of Acute Pain in the US in 2021. These cases are expected to grow at a moderate growth rate in the upcoming years. To overcome the existing treatment challenges several major pharma and biotech giants are developing novel therapies. Innovative approaches and emerging therapies, like SRP-001, are being developed to enhance acute pain treatment, offering a potential solution that prioritizes both effectiveness and safety, reducing the burden on patients and healthcare systems.

Novo Nordisk to Acquire Ocedurenone for Uncontrolled Hypertension from KBP Biosciences

Novo Nordisk A/S and KBP Biosciences PTE., Ltd. have unveiled a momentous development, with Novo Nordisk’s announcement of their agreement to acquire ocedurenone from KBP Biosciences. This innovative treatment, designed for uncontrolled hypertension and showing potential for cardiovascular and kidney disease applications, is set to change the landscape with a transaction valued at up to 1.3 billion US dollars.

Ocedurenone, an oral non-steroidal mineralocorticoid receptor antagonist (nsMRA), is currently undergoing phase III clinical evaluation in the CLARION-CKD trial. This study is focused on patients with advanced chronic kidney disease (CKD) and uncontrolled hypertension, characterized by persistently elevated blood pressure even after receiving two or more antihypertensive medications.

Martin Holst Lange, executive vice president and head of Development at Novo Nordisk, stated, “Hypertension stands as a primary risk factor for cardiovascular events, heart failure, chronic kidney disease, and premature death. We believe ocedurenone offers an exceptional benefit-risk profile and holds the potential to set new standards in the treatment of uncontrolled hypertension, addressing a significant medical gap for individuals living with cardiovascular and chronic kidney diseases.”

We are thrilled to hand over the reins of oprocedurenone to Novo Nordisk, a renowned global leader in chronic disease management. We firmly believe that this transfer can unlock oprocedurenone’s full potential, ultimately benefiting a broader range of patients worldwide suffering from cardiovascular and kidney diseases, stated Dr. Zhenhua Huang, founder and chairman of KBP Biosciences. Dr. Fred Yang, chief development officer of KBP Biosciences, further noted this transition marks a significant turning point in KBP’s journey as a relatively new player in the global pharmaceutical industry, with promising prospects in oprocedurenone’s research and development.

Ocedurenone has been the subject of scrutiny in nine clinical trials, notably the BLOCK-CKD Phase 2b trial. In this pivotal study, ocedurenone achieved its primary objective by delivering a noteworthy and statistically significant improvement in systolic blood pressure (SBP) from baseline to day 84 in patients grappling with stage 3b/4 CKD and uncontrolled hypertension. Notably, the trial did not report any instances of severe hyperkalemia or acute kidney injury associated with ocedurenone.

The CLARION-CKD phase III trial is now underway in the United States, Europe, and Asia, with the first patient dosed at the conclusion of 2021. The trial is proceeding according to plan, with an ambitious goal of randomizing over 600 patients across more than 150 sites. Novo Nordisk is also poised to launch phase III trials in additional cardiovascular and kidney disease indications in the coming years, with the aim of fully harnessing the potential of ocedurenone.

TAGRISSO Plus Chemotherapy Granted Priority Review in the US for Patients with EGFR-mutated Advanced Lung Cancer

AstraZeneca’s supplemental New Drug Application (sNDA) for TAGRISSO (osimertinib) combined with chemotherapy has been acknowledged and granted Priority Review in the United States. This expedited review is for the treatment of adult patients diagnosed with locally advanced or metastatic non-small cell lung cancer (NSCLC) exhibiting epidermal growth factor receptor mutations (EGFRm). The FDA bestows Priority Review status on drug applications that promise to bring significant improvements to the market, either through increased safety or efficacy, the prevention of severe conditions, or the enhancement of patient compliance. The Prescription Drug User Fee Act (PDUFA) date, representing the FDA’s deadline for a regulatory decision, is slated for the first quarter of 2024.

Annually, approximately 2.2 million individuals receive a global diagnosis of lung cancer, with 80-85% of these cases falling under the category of NSCLC, the most prevalent type of lung cancer. Roughly 70% of these patients are diagnosed with advanced NSCLC. Furthermore, in the United States and Europe, 10-15% of NSCLC patients, and in Asia, 30-40% of patients, exhibit EGFRm NSCLC. As per DelveInsight, in the US in 2022, there are approximately 200,000 new cases of lung cancer (~113,000 in men and ~88,000 in women). The society also reported that most lung cancer statistics include both small cell lung cancer and non-small cell lung cancer. About 10% to 15% of all lung cancers are SCLC, and about 80% to 85% are Non–Small Cell Lung Cancer.

Susan Galbraith, the Executive Vice President of Oncology R&D at AstraZeneca, emphasized, “The FLAURA2 results underpin TAGRISSO as a cornerstone in the first-line treatment of EGFR-mutated non-small cell lung cancer, extending median progression-free survival by an additional nine months when combined with chemotherapy. This option is especially vital for patients facing a poorer prognosis, including those with brain metastasis. We eagerly anticipate collaborating with the FDA to expedite the availability of this treatment regimen to patients.

The sNDA draws its foundation from the FLAURA2 Phase III clinical trial, which was prominently showcased at the Presidential Symposium during the 2023 World Conference on Lung Cancer (WCLC) organized by the International Association for the Study of Lung Cancer (IASLC). In this pivotal trial, the combination of TAGRISSO with chemotherapy demonstrated a remarkable 38% reduction in the risk of disease progression or mortality when compared to TAGRISSO monotherapy, which is the established first-line global standard of care. This significant difference was substantiated by a hazard ratio (HR) of 0.62 and a 95% confidence interval (CI) of 0.49-0.79, with a p-value of less than 0.0001.

In August 2023, the FDA granted Breakthrough Therapy Designation to the combination of TAGRISSO and chemotherapy for the initial treatment of adult patients with locally advanced or metastatic EGFRm NSCLC. TAGRISSO is authorized for use as a monotherapy in over 100 countries, including the US, EU, China, and Japan. Approved indications encompass first-line treatment for locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant treatment for early-stage (IB, II, and IIIA) EGFRm NSCLC.

FDA Awards Orphan Drug Designation to SLS009 in AML

SELLAS Life Sciences Group announced that the FDA has granted orphan drug status to SLS009 (formerly known as GFH009) for treating acute myeloid leukemia (AML) patients. SLS009 is an innovative, targeted CDK9 inhibitor currently undergoing assessment in a phase 1/2a clinical trial (NCT04588922) involving patients with relapsed/refractory AML and other blood-related cancers. Angelos Stergiou, MD, ScD hc, President and CEO of SELLAS, expressed gratitude for the FDA designation, emphasizing SLS009’s potential to address a critical unmet need in AML patients. The drug has displayed promising safety, initial efficacy, and anti-tumor activity.

Earlier, SELLAS shared favorable results from the phase 1 trial, demonstrating clinical activity and safety of SLS009 in relapsed/refractory lymphoma patients. The trial showcased an overall response rate (ORR) of 14.7% and a maximum 62% reduction in tumor burden among evaluated patients (n = 34). Notably, the ongoing trial is evaluating SLS009 in adults with confirmed relapsed/refractory hematologic malignancies, including AML, chronic lymphocytic leukemia/small lymphocytic lymphoma, and lymphoma.

The study’s phase 2a segment focuses on patients with relapsed/refractory AML, treating them with SLS009 in combination with azacitidine (Vidaza) and venetoclax. The primary study endpoints are assessing safety, tolerability, and efficacy at specified dosage levels. The company aims to expedite SLS009’s clinical development and provide hope to those battling AML, supported by the orphan drug designation. The phase 2a trial’s topline results are anticipated to be released by the end of 2023.

FDA Approves Adjuvant Nivolumab in Completely Resected Stage IIB/C Melanoma

The FDA granted approval to nivolumab (Opdivo, Bristol-Myers Squibb Company) for the adjuvant treatment of completely resected Stage IIB/C melanoma in patients aged 12 and above. The drug’s efficacy was assessed in a randomized, double-blind trial called CHECKMATE-76K (NCT04099251), which included 790 patients diagnosed with Stage IIB/C melanoma. The trial involved randomizing patients (2:1 ratio) to receive either nivolumab 480 mg or a placebo via intravenous infusion every 4 weeks for a maximum of 1 year or until disease recurrence or unacceptable adverse effects.

To be eligible for enrollment, patients needed to have a complete resection of the primary melanoma with negative margins and a negative sentinel lymph node within 12 weeks before randomization. Additionally, they needed to have an ECOG performance status of 0 or 1. Patients with ocular/uveal or mucosal melanoma, autoimmune disease, those requiring systemic treatment with corticosteroids (≥10 mg daily prednisone or equivalent) or other immunosuppressive medications, and those with prior melanoma therapy other than surgery were excluded from the trial. Randomization was stratified based on the AJCC 8th staging system edition (T3b vs. T4a vs. T4b).

The primary efficacy measure was recurrence-free survival (RFS), defined as the time from randomization to the first recurrence (local, regional, or distant metastasis), new primary melanoma, or death (from any cause), whichever occurred first, as determined by the investigator. Assessments were conducted at 26-week intervals during years 1-3 and every 52 weeks thereafter for 5 years. The median RFS was not reached in either the nivolumab arm (95% CI: 28.5, not reached) or the placebo arm (95% CI: 21.6, not reached) (hazard ratio=0.42 [95% CI: 0.30, 0.59]; p-value=<0.0001).

The most frequently reported adverse reactions (in ≥20% of patients) included fatigue, musculoskeletal pain, rash, diarrhea, and pruritus. The recommended nivolumab dosage for patients weighing 40 kg or more is 240 mg every 2 weeks or 480 mg every 4 weeks until disease progression or unacceptable toxicity for up to 1 year. For pediatric patients weighing less than 40 kg, the recommended dose is 3 mg/kg every 2 weeks or 6 mg/kg every 4 weeks until disease progression or unacceptable toxicity for up to 1 year.

This review was conducted under Project Orbis, a FDA Oncology Center of Excellence initiative facilitating concurrent submission and review of oncology drugs among international partners. The FDA collaborated with the Australian Therapeutic Goods Administration (TGA), Health Canada, Israel’s Ministry of Health (IMoH), and Switzerland’s Swissmedic for this review. The application reviews are ongoing at other regulatory agencies. The review utilized the Real-Time Oncology Review (RTOR) pilot program, streamlining data submission before the complete clinical application filing, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

FDA Grants Fast Track Designation to SurVaxM in Newly Diagnosed Glioblastoma

On October 12, 2023, MimiVax, Inc. revealed that the United States Food and Drug Administration (USFDA) had granted Fast Track Designation (FTD) to its SurVaxM vaccine, which is under investigation for its potential in treating newly diagnosed glioblastoma (nGBM).

“The receipt of Fast Track Designation affirms the importance of new clinical developments of novel therapies to improve the treatment and outcomes for patients with newly diagnosed glioblastoma,” said Michael Ciesielski, CEO of MimiVax. “This designation is a key component in our journey to help patients with glioblastoma to live longer.”

The SURVIVE trial, a Phase 2b clinical study of SurVaxM for newly diagnosed glioblastoma (nGBM), is currently in the process of recruitment at 11 cancer centers throughout the United States. Encouraging results from a previous Phase 2a trial of SurVaxM for nGBM, as published in the Journal of Clinical Oncology, revealed that 51% of patients who received SurVaxM survived for a minimum of 2 years, and 41% survived for at least 3 years. Furthermore, the median Overall Survival for patients with nGBM in this study was notably longer at 25.9 months when compared to what is typically expected with standard therapy alone.

SurVaxM is formulated to introduce a groundbreaking approach in the Glioblastoma therapeutics field. SurVaxM stands out as a pioneering, patented peptide mimic immunogen designed to specifically target survivin, a cell-survival protein found in 95% of glioblastomas, as well as numerous other cancer types. SurVaxM works to trigger the patient’s innate immune response, with the goal of regulating tumor growth and deterring disease relapse. Given survivin’s prevalence in a wide range of cancers, SurVaxM potentially holds promise for application in other cancer types as well. MimiVax’s primary focus is on the successful completion of the Phase 2b SURVIVE trial and obtaining the essential funding to guide SurVaxM through the FDA approval process. 

Glioblastomas pose a significant healthcare burden due to their aggressive nature. As per DelveInsight, the total glioblastoma-diagnosed incident population in the 7MM was 32,500+ in 2021 and the number of cases is projected to increase during the forecast period. Companies are actively striving to enhance treatment options and outcomes through innovative therapies and research. Several major pharma and biotech giants such as MimiVax, among others, are actively involved in the development of novel therapies in the market.