ImPact Biotech Receives FDA Clearance of IND Application for Padeliporfin VTP in Pancreatic Cancer

ImPact Biotech, a biotechnology company in its clinical stage dedicated to advancing Padeliporfin Vascular Targeted Photodynamic (VTP) therapy for various solid tumors, announced on December 20, 2023, that the U.S. Food and Drug Administration (FDA) has granted clearance for the Company’s Investigational New Drug (IND) application that allows the commencement of a Phase 1 study targeting patients with unresectable pancreatic adenocarcinoma (PDAC).

Padeliporfin VTP (Vascular Targeted Photodynamic) therapy represents a minimally invasive approach in oncology for addressing solid tumors. This treatment method provides an efficacy comparable to surgery while prioritizing the preservation of healthy tissue or organs. VTP involves administering an inactive drug, Padeliporfin, intravenously. Upon exposure to light, this drug promptly induces the restriction of blood supply exclusively in the illuminated region, leading to focused tumor necrosis. This, in turn, triggers antitumor immune responses, bolstering the elimination of cancer cells.

We are excited to explore the potential of Padeliporfin VTP in addressing the tremendous unmet need in locally advanced Pancreatic Cancer and look forward to initiating this study in the first half of next year,” said Barak Palatchi, CEO of ImPact Biotech. “Moreover, alongside our ongoing pivotal study in upper tract urothelial cancer and plans to evaluate Padeliporfin VTP in non-small cell lung cancer, clearance of this IND reflects broadly held conviction in our platform as a non-surgical alternative with potential to improve outcomes and expand the treatable population of patients across a range of solid tumors.

The Phase 1 study consists of two segments, conducted across multiple centers, employing a non-randomized, open-label approach. Its purpose is to examine the safety, tolerance, pharmacokinetics, pharmacodynamics, and initial effectiveness of Padeliporfin VTP therapy among patients diagnosed with Stage 3, locally advanced, and unresectable PDAC. 

Part A will adopt a 3+3 dose-escalation format to assess the safety and tolerance of Padeliporfin VTP. This phase will involve administering escalating doses of VTP through endovascular means via an optical fiber, combined with a fixed intravenous dosage of Padeliporfin. Part B will enroll an expansion group, utilizing either the maximum tolerated dose identified in Part A or the recommended expansion dose. The primary objective of this phase is to evaluate the preliminary effectiveness of the treatment.

In 2021, the total incident cases of Pancreatic Cancer in the 7MM countries were 175,700+ cases, and these cases are anticipated to increase in the upcoming years. Among the European countries, Germany had the highest incident cases of Pancreatic Cancer in 2021, i.e., 21,800+ cases, followed by France which had 14,900+ incident cases in 2021. On the other hand, Spain had the lowest incident cases of Pancreatic Cancer, i.e. 8,500+ cases in 2021. Japan had 43,100+ incident cases of Pancreatic Cancer in 2021. Along with ImPact Biotech, several other major pharma and biotech companies are evaluating theory drug candidates in various stages of clinical development to overcome the existing treatment challenges in the Pancreatic Cancer therapeutics market

Ocelot Bio Receives FDA Orphan Drug Designation for OCE-205 for the Treatment of Ascites

On December 20, 2023, Ocelot Bio, Inc., a clinical-stage biopharmaceutical company specializing in pioneering therapeutics for addressing complications related to end-stage liver disease (ESLD), announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to their primary candidate, OCE-205. This designation is specifically for treating ascites stemming from all causes except cancer.

Ocelot Bio’s primary asset, OCE-205, stands as a therapeutic peptide with a distinct mechanism of action that holds promise in enhancing outcomes for individuals facing complications arising from end-stage liver disease (ESLD). The uniqueness of OCE-205 stems from its formulation as a peptide combining agonist and antagonist properties, specifically targeting the vasopressin 1a (V1a) receptor while lacking activity on the vasopressin 2 (v2) receptor, even at concentrations significantly higher than those utilized in ESLD therapy. 

By possessing both V1a agonist and antagonist attributes, OCE-205 therapy aims to alleviate portal hypertension while maintaining a ceiling on its maximal effectiveness. This feature helps prevent excessive vasoconstriction, a concern associated with full agonists that can lead to ischemic injuries and potentially severe adverse effects like respiratory failure. Furthermore, by excluding V2 activity, OCE-205 treatment aims to steer clear of fluid retention and overload issues.

The Phase 2 clinical trial, focusing on assessing OCE-205 for treating hepatorenal syndrome accompanied by acute kidney injury (HRS-AKI) (NCT05309200), has successfully completed its enrollment. Concurrently, clinical investigations targeting ascites are projected to commence in 2024. Notably, the U.S. Food and Drug Administration (FDA) granted an Orphan Drug Designation for OCE-205’s utilization in treating hepatorenal syndrome in 2022 and extended this designation to include ascites in 2023.

“The FDA granting Orphan Drug Designation for OCE-205 in ascites is validation of the tremendous need for improved therapies offering novel approaches for patients and supports our clinical focus on this important indication,” said Lise Kjems, M.D., Ph.D., chief medical officer at Ocelot Bio. “This milestone serves as a catalyst as we work with patients, healthcare professionals and health authorities to pave a brighter path forward for these patients who have limited treatment options. We are well positioned to further advance our clinical development program for OCE-205 and look forward to progressing this program in ascites.”

The Orphan Drug Designation offers Ocelot Bio specific advantages, including financial support for clinical development and the prospect of up to seven years of exclusive market rights in the U.S. for the drug’s specified orphan indication if it obtains final approval for that particular designation. Ocelot Bio intends to commence clinical investigations of OCE-205 targeting refractory ascites in the year 2024. 

Ascites signify an abnormal buildup of fluid in the abdominal cavity, serving as a key indicator of the transition into the decompensated phase of cirrhosis. As per DelveInsight, in 2020, the total cases of Ascites due to cirrhosis in the 7MM were 240,700+. In 2020, there were 26,800+ and 122,200+ cases of Grade I and Grade II & III ascites due to cirrhosis in the United States. Among the EU-5 countries, the highest cases of Ascites due to cirrhosis were found in Germany (20,004), followed by the UK (15,845) and France (11,138). The least cases of Ascites due to cirrhosis were found in Spain (4,904). There were 29,571 cases of ascites due to cirrhosis in Japan in 2020. The current approaches for ascites management are restricted, often involving invasive procedures carrying significant risks and challenges for patients. This highlights the urgent necessity for innovative advancements that can enhance outcomes for individuals grappling with this debilitating condition. Globally, several major pharma and biotech giants are actively working in the Ascites therapeutics market to overcome the existing treatment challenges. 

Amylyx Pharmaceuticals Announces First Participant Dosed in the Global Phase 3 ORION Study of AMX0035 in Progressive Supranuclear Palsy

Amylyx Pharmaceuticals, Inc. (NASDAQ: AMLX) announced that the initial participant has received medication in ORION, a Phase 3 clinical trial examining AMX0035 (sodium phenylbutyrate [PB] and taurursodiol [TURSO]) as a treatment for Progressive Supranuclear Palsy (PSP). This randomized, double-blind, placebo-controlled trial aims to enroll around 600 participants across approximately 100 sites in the United States, Canada, the European Union, the United Kingdom, and Japan. It stands as the largest Progressive Supranuclear Palsy clinical trial conducted to date.

AMX0035 constitutes an oral, fixed-dose combination consisting of sodium phenylbutyrate and taurursodiol (known as ursodoxicoltaurine outside of the U.S.). It has received approval in the U.S. as RELYVRIO® for treating amyotrophic lateral sclerosis (ALS) in adult patients. In Canada, it has been conditionally approved as ALBRIOZA™ for ALS treatment. Importantly, the formulation of RELYVRIO, ALBRIOZA, and AMX0035 remains identical. Furthermore, apart from its established usage in ALS, AMX0035 is under investigation for potential treatment applications in various other neurodegenerative diseases. Amylyx is exploring its potential in treating diverse populations in different geographical regions.

The primary efficacy endpoint of the trial will focus on assessing the alteration in disease progression from the baseline to Week 52. This measurement will be based on the total score derived from the 28-item Progressive Supranuclear Palsy Rating Scale (PSPRS), a well-established and validated endpoint commonly used in Progressive Supranuclear Palsy clinical trials.

The secondary efficacy endpoints encompass multiple measurements:

  • Disease progression, evaluated through a modified 10-item PSPRS score.
  • Motor aspects concerning activities of daily life, assessed via the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part 2 (MDS-UPDRS Part II).
  • In addition to these secondary endpoints, the trial will explore various other outcomes, including changes in activities of daily living, cognitive function, quality of life, overall survival, brain regional volumes, fluid biomarkers indicating neuronal injury or inflammation, and the impact on caregiver burden.

The assessment of safety and tolerability will involve monitoring the occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Participants who complete the initial 52-week randomized, placebo-controlled phase of the trial will have the opportunity to participate in an Open-Label Extension. During this extension phase, all participants will receive AMX0035 for an additional year.

Anticipated timelines suggest that the top-line results from this trial are expected to be available within 2–3 years.

“There is a pressing unmet need within the PSP community for new and effective treatment options, as no disease-modifying therapies have been approved for the treatment of the disease,” said Dr. Kristophe Diaz, Executive Director and Chief Science Officer at CurePSP. “We’re looking forward to continuing our collaboration on ORION, recognizing that a united global effort is essential to usher in promising advancements and raise awareness for people living with PSP and their families.”

“Given PSP is a relentlessly progressive disease, it is imperative that we respond to the unmet needs of the community with a sense of urgency. Our current focus is on activating clinical trial sites in all participating regions in order to complete the trial as quickly and efficiently as possible, gearing toward what could potentially be the first therapy for the PSP community,” said Lahar Mehta, MD, Head of Global Clinical Development at Amylyx.

Progressive Supranuclear Palsy, stands as an infrequent, sporadic neurodegenerative ailment typically observed in adults. This disorder impacts various functions such as walking, balance, eye movement, swallowing, and speech. PSP commonly starts in the later stages of middle age and exhibits a swift progression over time. Globally, around seven out of 100,000 individuals are affected by this condition. In 2022, the total prevalent cases of Progressive Supranuclear Palsy were estimated to be approximately 80,700+ cases in the 7MM and the cases are projected to increase in the upcoming years. In the US, there were approximately 21,000+ prevalent cases of Progressive Supranuclear Palsy in 2022. Among the 7MM, Japan accounted for the highest prevalent cases of Progressive Supranuclear Palsy, contributing nearly 29%, while Spain accounted for the least with nearly 7% of the total prevalent cases. 

Individuals diagnosed with Progressive Supranuclear Palsy generally have a life expectancy of six to eight years from the time of initial diagnosis. Presently, there are no approved therapies intended to modify the course of the disease for individuals with Progressive Supranuclear Palsy. The PSP community faces a critical and urgent requirement for novel and efficacious treatment alternatives, given the absence of approved therapies capable of modifying the progression of this disease. Globally, several major pharma and biotech giants including Amylyx Pharmaceuticals, among others, are actively working in the Progressive Supranuclear Palsy therapeutics market to overcome the existing treatment challenges. 

SELLAS Receives FDA Orphan Drug Designation for SLS009 for Treatment of Peripheral T-cell Lymphomas

SELLAS Life Sciences Group has announced the approval of Orphan Drug Designation (ODD) for their innovative CDK9 inhibitor, SLS009, by the U.S. Food and Drug Administration (FDA) for addressing relapsed/refractory Peripheral T-cell Lymphomas (PTCL).

Angelos Stergiou, MD, ScD h.c., President and CEO of SELLAS, expressed enthusiasm about this milestone, emphasizing its significance following the recent FDA Fast Track Designation for PTCL. He highlighted SLS009’s positive outcomes in the Phase 1 trial for r/r hematological malignancies, showcasing clinical responses in PTCL, including instances of complete response. The compound exhibited a promising safety profile, robust initial efficacy signals, and signs of anti-tumor activity, driving both Phase 1 and ongoing Phase 2 studies. With these designations secured, the company is eager to advance SLS009’s development, collaborating closely with regulators to bring this treatment to those in need.

SLS009 is presently undergoing assessment in a Phase 1b/2 trial focusing on r/r PTCL. This study, funded by GenFleet Therapeutics, Inc. in China, aims to enroll up to 95 patients, evaluating safety, efficacy, and potentially serving as a registrational study based on outcomes.

Notably, the Phase 1 trial’s dose-escalation phase demonstrated SLS009’s favorable safety and promising clinical efficacy in r/r hematological malignancies. Encouraging responses were observed in patients with acute myeloid leukemia and lymphoma, particularly in PTCL cases. The responses surpassed those seen with the current standard of care, belinostat, in a similar patient population. Furthermore, patients achieving complete response with SLS009 had prior treatments involving an HDAC inhibitor.

The Orphan Drug Designation by the FDA offers various benefits to aid drug developers in addressing rare diseases or conditions, including support throughout the drug development process, tax credits for qualifying clinical expenses, exemptions from specific FDA fees, and seven years of marketing exclusivity.

Apnimed Announces First Patient Dosed in SynAIRgy, the Second Phase 3 Clinical Study of AD109, a Potential Nighttime Oral Treatment for Obstructive Sleep Apnea

Apnimed has initiated dosing the first patient in its SynAIRgy Phase 3 investigation, aiming to assess the effectiveness and safety of AD109 (aroxybutynin/atomoxetine) over a six-month period compared to a placebo. AD109 carries the promise of being the inaugural nighttime oral pharmacological remedy for individuals affected by Obstructive Sleep Apnea (OSA) who either cannot tolerate or decline Positive Airway Pressure (PAP) therapy.

Presently, less than half of the individuals employing PAP therapy maintain long-term compliance, leaving a significant number susceptible to the untreated repercussions of OSA, including heightened risks of stroke and heart attack.

Dr. Larry Miller, CEO of Apnimed, underscored the significance of the LunAIRo and SynAIRgy trials as the most extensive prospective appraisals of a novel pharmacological approach for OSA. These trials represent a crucial stride toward developing a potential treatment catering to patients with limited or no alternative options. Uncovering and testing alternative therapies for OSA is essential to potentially enhance patients’ quality of life during both nocturnal rest and daytime wakefulness. Pending the outcomes, AD109 holds the potential to revolutionize OSA treatment. The Phase 3 program’s top-line findings for AD109 are anticipated in the initial half of 2025.

Obstructive Sleep Apnea (OSA) imposes a substantial burden on individuals and healthcare systems worldwide. The rising prevalence of OSA, coupled with its associated health risks like cardiovascular problems and cognitive impairment, underscores the need for effective interventions. Companies such as Apnimed, among others, are operating within the Obstructive Sleep Apnea market and play a crucial role in developing innovative therapies aimed at managing and treating OSA.