Versanis chairman and CEO Mark Pruzanski, M.D., added, “It has been a privilege for our team to advance bimagrumab to address one of the greatest health crises of our time.” Lilly is best positioned to realize the potential of bimagrumab in combination with its incretin treatments to benefit individuals living with cardiometabolic disorders as a global leader in producing life-changing medications.”
Versanis stockholders might earn up to $1.925 billion in cash under the terms of the agreement, which includes an initial payment and additional payments based on specific development and sales objectives. The deal is subject to the usual closing conditions. Upon completion, Lilly will decide whether this deal is a business combination or an asset acquisition, including any relevant acquired in-process research and development charges, in accordance with Generally Accepted Accounting Principles (GAAP). This transaction will be reflected in Lilly’s financial performance and financial guidance in the future.
FDA Approves Beyfortus for Prevention of RSV in Infants
Beyfortus (nirsevimab) from AstraZeneca and Sanofi has been approved in the United States for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in newborns and infants born during or entering their first RSV season, as well as children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Beyfortus will be available in the United States ahead of the following RSV season in 2023-2024.
The FDA approval follows a unanimous vote by the Antimicrobial Drugs Advisory Committee (AMDAC) on the favorable benefit-risk profile of Beyfortus, and is based on Beyfortus’ extensive clinical development program, which includes three pivotal late-stage clinical trials. A single dose of Beyfortus revealed consistent efficacy against RSV LRTD across all clinical endpoints for five months, the span of a typical RSV season. Beyfortus is the first preventative option approved to protect a wide range of infants, including those born healthily at term, prematurely, or with certain health issues that leave them vulnerable to severe RSV sickness. The single dose can be given at the start of the RSV season or at birth for individuals born during the RSV season.
“Beyfortus represents an opportunity for a paradigm shift in preventing serious respiratory disease due to RSV across a broad infant population in the US,” said Iskra Reic, Executive Vice President, Vaccines and Immune Therapies at AstraZeneca. Beyfortus’ research highlights AstraZeneca’s continuous leadership in meeting the needs of the most disadvantaged groups and decreasing the burden on healthcare systems.”
RSV is the leading cause of hospitalization for infants under the age of one in the United States, with a yearly rate that is 16 times that of influenza. An estimated 590,000 RSV disease cases in infants under one year old require medical attention each year, including physician’s office, urgent care, emergency room, and hospitalizations. Beyfortus was well tolerated in general, having a favorable safety profile that was consistent across all clinical trials. Beyfortus and placebo had comparable overall rates of adverse events, with the majority of adverse events being mild or moderate in severity. Rash and injection site responses were the most common adverse effects.
Beyfortus was authorized in the European Union in October 2022 for the prevention of RSV LRTD in newborns and babies during their first RSV season. Regulatory applications are also being reviewed in China, Japan, and several other nations.
Alnylam Reports Updated Positive Interim Phase 1 Results for ALN-APP
Alnylam Pharmaceuticals announced positive updated interim findings from the initial phase of the Phase 1 study of ALN-APP, a potential RNAi treatment designed to target amyloid precursor protein (APP) for Alzheimer’s disease and cerebral amyloid angiopathy (CAA). The company presented these findings at the 2023 Alzheimer’s Association International Conference (AAIC) held in Amsterdam, The Netherlands from July 16-20, 2023. ALN-APP represents the first clinical-stage program that utilizes Alnylam’s proprietary C16-siRNA conjugate platform for delivering therapeutics to the central nervous system (CNS). Additionally, it is the first RNAi treatment under investigation to demonstrate gene suppression in the human brain. Alnylam Pharmaceuticals is working on the development of ALN-APP in collaboration with Regeneron Pharmaceuticals, Inc.
Part A of the ongoing Phase 1 study has enrolled twenty patients who have early-onset Alzheimer’s disease. These patients were divided into three groups and received a single dose of ALN-APP through intrathecal injection. The administration of ALN-APP in single doses has been well tolerated thus far, with all reported adverse events being of mild or moderate severity. There were no notable increases in white blood cell count or total protein levels in the cerebrospinal fluid (CSF) compared to the baseline. Routine laboratory assessments including hematology, serum chemistry, liver function, urinalysis, and coagulation, as well as preliminary data for the exploratory biomarker neurofilament light chain (NfL), did not indicate any significant abnormalities.
Patients who received a single dose of 75mg ALN-APP experienced a rapid and sustained decrease in the levels of soluble APPα (sAPPα) and soluble APPβ (sAPPβ) in the cerebrospinal fluid. These biomarkers are indicative of engagement with the target. The maximum reductions observed were 84% for sAPPα and 90% for sAPPβ. At the six-month mark following the single dose, there were sustained mean reductions of more than 55% for sAPPα and more than 65% for sAPPβ. For more detailed results, please refer to the presentation on Capella.
The ongoing study continues to investigate the effects of single doses of ALN-APP in Part A. Additionally, the safety review committee has suggested commencing Part B, which involves multiple doses of the treatment. Patients from Part A will be enrolled in Part B, and regulatory approval has already been obtained to proceed with this phase in Canada, where most of the Part A patients were enrolled. However, in the United States, the multiple-dose portion of the study is currently under a partial clinical hold. This hold is due to observations made in previous non-clinical toxicology studies, which revealed certain findings.
Alongside ALN-APP, Alnylam Pharmaceuticals and Regeneron Pharmaceuticals have identified ten targets within the central nervous system (CNS) as part of their exclusive collaboration established in 2019. The objective of this collaboration is to develop RNA interference (RNAi) therapeutics for diseases affecting the eye and the CNS.
FDA Accepts NDA for Rivoceranib Plus Camrelizumab in Unresectable HCC
Elevar Therapeutics declared that the U.S. Food and Drug Administration (FDA) has accepted their new drug application (NDA) for rivoceranib. Rivoceranib, an oral TKI (tyrosine kinase inhibitor), is being investigated in combination with camrelizumab, a PD-1 inhibitor, as a potential first-line treatment for unresectable hepatocellular carcinoma (uHCC). The FDA has set a target action date, known as the Prescription Drug User Fee Act (PDUFA) target action date, for May 16, 2024. Elevar Therapeutics is a majority-owned subsidiary of HLB Co., Ltd.
The new drug application (NDA) for rivoceranib is backed by clinical data obtained from the Phase 3 CARES 310 study (NCT03764293). The study evaluated the combination of rivoceranib and camrelizumab, and the results demonstrated statistically significant and clinically meaningful improvements in overall survival (OS), progression-free survival (PFS), and overall response rate compared to sorafenib, which is a standard first-line treatment for unresectable hepatocellular carcinoma (uHCC).
The international trial included 543 patients and was conducted at 95 study sites across 13 countries/regions. The combination of camrelizumab and rivoceranib showed a median OS of 22.1 months (with a 95% confidence interval of 19.1-27.2), whereas sorafenib had a median OS of 15.2 months (with a 95% confidence interval of 13.0-18.5). The hazard ratio was 0.62 (with a 95% confidence interval of 0.49-0.80), indicating a significant reduction in the risk of death with the camrelizumab + rivoceranib combination compared to sorafenib (p<0.0001, one-sided).
In terms of progression-free survival (PFS), the camrelizumab + rivoceranib combination showed a median PFS of 5.6 months (with a 95% confidence interval of 5.5-6.3), whereas sorafenib had a median PFS of 3.7 months (with a 95% confidence interval of 2.8-3.7). The hazard ratio was 0.52 (with a 95% confidence interval of 0.41-0.65), indicating a significant reduction in the risk of disease progression or death with the combination therapy (p<0.0001, one-sided).
Furthermore, the confirmed objective response rate for the camrelizumab + rivoceranib combination was 25.4% (with a 95% confidence interval of 20.3-31.0), while sorafenib had an objective response rate of 5.9% (with a 95% confidence interval of 3.4-9.4). These results indicate a substantially higher rate of tumor response with the combination therapy compared to sorafenib.
The efficacy results of the combination therapy remained consistent across various subgroups, indicating its potential benefits for the overall global population with unresectable hepatocellular carcinoma (uHCC). The treatment also demonstrated efficacy in patients with uHCC caused by both hepatitis C virus and non-viral factors, which represent the majority of liver cancer cases in the United States.
In February 2023, the National Medical Products Administration (NMPA) in China approved the combination therapy of rivoceranib and camrelizumab as a first-line treatment for liver cancer.
Elevar Therapeutics is not only focusing on the combination therapy for uHCC but is also developing rivoceranib as a standalone treatment option for adenoid cystic carcinoma (ACC). Additionally, they are exploring the use of rivoceranib as both monotherapy and in combination with other therapies for various types of tumor cells.
Karyopharm Receives FDA Fast Track Designation for Selinexor for the Treatment of Myelofibrosis
On July 17, 2023, Karyopharm Therapeutics Inc. (Nasdaq: KPTI) announced that the United States Food and Drug Administration (FDA) has granted Fast Track Designation to the development program of selinexor for the treatment of patients with Myelofibrosis, including primary Myelofibrosis, post-essential thrombocythemia Myelofibrosis, and post-polycythemia vera Myelofibrosis.
Karyopharm began the Phase 3 clinical research (XPORT-MF-034) (NCT04562389) in June 2023 to examine the effectiveness and safety of once-weekly selinexor 60 mg combined with ruxolitinib in Myelofibrosis patients who have never taken JAKi inhibitors. Updated data from the Phase 1 study, demonstrated rapid, deep, and sustained spleen responses and robust symptom improvement in patients treated with selinexor 60 mg in combination with ruxolitinib as of the cut-off date of April 10, 2023, were presented at the American Association for Cancer Research Annual Meeting 2023, American Society of Clinical Oncology 2023, and European Haematology Association 2023. Phase 3 study top-line results are anticipated in 2025. To help the maximum number of patients, the company intends to broaden its clinical development program for Myelofibrosis by examining selinexor in other JAKi-naive contexts, such as novel combinations.
Fast Track Designation for selinexor highlights its potential to address the unmet medical need in Myelofibrosis, an important acknowledgement as we continue our pivotal Phase 3 study,” said Reshma Rangwala, MD, PhD, Chief Medical Officer of Karyopharm. “Selinexor’s unique mechanism of action, XPO1 inhibition, is a novel and potentially fundamental mechanism in Myelofibrosis. We have been highly encouraged by the efficacy and safety data observed to date [in our Phase 1 study] with selinexor in combination with ruxolitinib in patients with treatment-naïve Myelofibrosis and believe selinexor has the potential to shift the treatment paradigm. We look forward to continued interaction with the FDA as we advance the development of this promising treatment for patients in need.
As per DelveInsight, the total prevalent population of Myelofibrosis in the 7MM was 39,700+ in 2021 and is projected to increase in the upcoming years. In the United States, the total number of prevalent cases of Myelofibrosis was 19,800+ in the year 2021. Myelofibrosis can be further categorized into primary Myelofibrosis and secondary Myelofibrosis. In 2021, primary Myelofibrosis accounted for 75% of all cases in the US. Similarly, among the EU-5 countries, Germany accounted for the highest number of Myelofibrosis diagnosed prevalent cases, followed by the UK, whereas Spain accounted for the lowest number of cases in 2021.
The treatment goal for most patients with Myelofibrosis is to relieve symptoms, reduce an enlarged spleen, improve blood cell counts (i.e., anemia), and reduce the risk of complications. The anticipated approval and launch of Selinexor, is expected to improve the treatment landscape of Myelofibrosis. Similarly, several other major pharma and biotech giants such as GSK, AbbVie, Incyte Corporation, Celgene/BMS, and MorphoSys, among others are engaged in developing therapies to address these unmet needs of patients.
Adcentrx Therapeutics Announces FDA Clearance of IND Application for ADRX-0706 for the Treatment of Advanced Solid Tumors
On July 17, 2023, Adcentrx Therapeutics (“Adcentrx”), announced that the US FDA has cleared the company’s Investigational New Drug (IND) application of ADRX-0706 for the treatment of select advanced solid tumors. ADRX-0706 is an ADC product candidate discovered by Adcentrx. Nectin-4, a cell surface adhesion protein that is overexpressed in a variety of human malignancies and is linked to a poor prognosis for the disease, is the target of the antibody component. The ADC is manufactured using a proprietary conjugation technology and novel tubulin inhibitor payload to generate an ADC with a drug-antibody ratio of eight (DAR 8). In preclinical models, ADRX-0706 showed a positive pharmacokinetic and safety profile, as well as considerable efficacy for a number of tumor indications.
“The FDA’s acceptance of our IND application is an exciting milestone for Adcentrx,” said Hui Li, Ph.D., Founder and Chief Executive Officer of Adcentrx. “As our first program to receive FDA clearance, we are one step closer to bringing our novel ADC technology to patients in need across the oncology landscape.”
“ADRX-0706 demonstrated a remarkable efficacy and safety profile in preclinical studies,” added Pia Challita-Eid, Ph.D., Chief Scientific Officer of Adcentrx. “We are thrilled to be progressing our first program into the clinic as we continue to apply our optimized ADC platform on a robust and differentiated product pipeline.”
As per the update from ADRX-0706 will undergo an open-label, multicenter, non-randomized dose escalation and dose expansion trial for its first-in-human Phase 1a/1b clinical trial. Patients with specific advanced solid tumors will be enrolled in the study. The primary objectives of the study will be to characterize the safety and tolerability of ADRX-0706 and determine the optimal dose of ADRX-0706, a major goal. The first patient is anticipated to be enrolled in the study in the second half of 2023, and the first data readout is anticipated in the middle of 2024.
Solid tumors refer to abnormal masses or growths that develop in tissues or organs of the body. Unlike liquid tumors such as leukemia, solid tumors form in a specific location and often maintain their shape. These tumors can occur in various organs and tissues, including the lungs, breasts, colon, prostate, liver, brain, and others. Treatment of solid tumor plans depends on factors such as tumor type, stage, location, and individual patient characteristics. Due to their diverse nature, solid tumors require personalized and multidisciplinary approaches for effective management. Ongoing research and advancements in medical science aim to improve diagnostic techniques, develop more targeted therapies, and enhance overall outcomes for individuals affected by solid tumors. The development of pipeline therapies such as ADRX-0706, among others, is anticipated to transform the Advanced Solid Tumors’ treatment scenario in the upcoming years.
