Dapansutrile

The number of diagnosed prevalent cases of gout will be 25,961,819 in 2032, according to GlobalData. Credit: ThamKC via Shutterstock. France-based biotechnology company PK Med has received clearance from the US Food and Drug Administration (FDA) to advance its injectable gout treatment PKM-01 into Phase II clinical trials, without undergoing Phase I studies. The Phase II trial will evaluate three doses of PKM-01, a combined treatment of controlled-release colchicine with ropivacaine, an anaesthetic. The prospective, randomised study aims to select the optimal dose of the treatment to further advance it into Phase III trials. PKM-01 is an intra-articular injectable treatment candidate for gout flares. Unlike current treatment regimens, ropivacaine’s anaesthetic effect is expected to alleviate pain within minutes of injection. Oral colchicine, a standard anti-inflammatory treatment for gout, can only be used in low doses due to toxicity and systemic exposure. PKM-01’s localised colchicine delivery aims to offer potent, lasting pain and inflammation relief without the systemic risks associated with standard-of-care treatments. Gout is a type of arthritis that occurs when there is a buildup of uric acid in the body, leading to the formation of urate crystals in the joints. This can cause sudden and severe pain, swelling, and inflammation – typically in the big toe but can affect other joints as well. According to a report on GlobalData’s Pharmaceutical Intelligence Center, the number of diagnosed prevalent cases of gout is predicted to be 25,961,819 in 2032. The gout market is forecast to be worth $10.77bn in 2032, an increase from $4.63bn in 2022. See Also: Streamlining supply chain operations in focus at Clinical Trial Supply Europe 2024 FDA approves Alvotech-Teva’s SIMLANDI jab for multiple conditions GlobalData is the parent company of Pharmaceutical Technology. There are several therapies in the late-stage pipeline for gout, most of which are urate-lowering therapies or anti-inflammatory therapies, one of which being Dapansutrile, an inflammasome inhibitor forecast to launch in 2026 – potentially offering an improved safety profile for long-term use compared to the current treatment regimen of nonsteroidal anti-inflammatory drugs, corticosteroids, and colchicine, as per a GlobalData analyst. In the 26 February announcement accompanying the FDA clearance, PK Med CEO Gauthier Pouliquen said: “This FDA feedback is excellent news for clinicians and patients suffering from gout flares. It should significantly accelerate the time-to-market for PKM-01. PK MED is now entering the fund-raising phase to finance PKM-01 Phase II clinical trials. With robust patent protection and a clear path to deliver Phase II results, PKM-01 represents an attractive and low-risk opportunity for investors and partners.”

NEW YORK--( BUSINESS WIRE )--Olatec Therapeutics, Inc. (Olatec), a leader in the developing class of selective NLRP3 inhibitors, today announced that Cure Parkinson’s granted an award to initiate a Phase 2 clinical trial investigating the potential of oral dapansutrile to slow or stop the progression of Parkinson’s disease. Parkinson’s is a complex neurodegenerative disease, which as reported by Cure Parkinson’s, is the fastest growing neurological condition in the world. The symptoms of Parkinson’s are treated with a range of medications, but despite decades of research, currently there remains a serious unmet need for a treatment to slow, stop or reverse the progression of this disease. The movement-associated symptoms of Parkinson’s are mainly caused by the loss of dopamine-producing nerve cells (dopaminergic neurons) in the mid-brain called the substantia nigra which controls movement. This loss of dopaminergic neurons is associated with accumulation of a protein known as α-synuclein within neurons, which is thought to disrupt their function. There is growing scientific literature suggesting that inflammation contributes to the damage and loss of neurons in the brain in Parkinson’s patients. In particular, there is evidence that the NLRP3 inflammasome is activated within the inflammatory cells of the brain, called microglia, and this activation may be triggered by abnormal aggregates of α-synuclein protein. Treatment with dapansutrile has the potential to arrest this cyclical process of cell damage thereby slowing the progression of the disease. This investigator-initiated study entitled “Anti-inflammatory Intervention with Dapansutrile (OLT1177 ® ) for Parkinson’s Disease Modification (DAPA-PD): A Randomised Double-Blind Placebo-Controlled Phase II Trial” is targeting to commence in mid-2024, subject to completion of all contractual agreements and regulatory authorizations. The trial will seek to enroll 36 participants with early Parkinson’s disease. Treatment duration will be six months with placebo control, followed by an optional, six month open-label phase. This single center study will be conducted at the John van Geest Centre for Brain Repair, Department of Clinical Neurosciences at the University of Cambridge in the UK. Dr. Caroline H. Williams-Gray, who leads the Cambridge Parkinson’s Disease Research Clinic, is the Principal Investigator. When asked about the study, Dr. Caroline Williams-Gray, said: “There is a pressing need for a specific treatment, such as dapansutrile, which targets the most relevant aspects of the immune activation pathway in Parkinson’s without causing general immunosuppression and leading to unwanted side effects. In this trial, we aim to determine dapansutrile’s safety and tolerability in patients with Parkinson’s, and to establish whether treatment with dapansutrile can reduce inflammation in both the brain and periphery in Parkinson’s. We will also investigate whether this results in a positive effect on clinical symptoms and disease progression.” Olatec’s Founder and CEO, Damaris Skouras commented: “The grant from Cure Parkinson’s and our collaboration with Dr. Williams-Gray at the University of Cambridge provides the possibility to advance dapansutrile in its first CNS indication as a potential disease modifying treatment for Parkinson’s.” About Parkinson’s Disease Over 9 million people worldwide are living with Parkinson’s disease ( mdabstracts.org , 2020). Currently, there are no therapeutics that can alter Parkinson’s disease progression. Patients initially present with complaints of changes in movement, walking and speech; worsening physical symptoms are accompanied by the development of cognitive decline as well as a range of other non-motor symptoms including mood disturbance, bladder and bowel dysfunction, sleep problems and difficulties with blood pressure control. Medications such as levodopa can improve movement symptoms but are unable to control the wide range of non-motor symptoms that affect people with Parkinson’s disease, and do not alter disease progression. About Scientific Rationale for NLRP3 in Parkinson’s Disease The movement-associated symptoms of Parkinson’s are mainly caused by the loss of dopamine-producing nerve cells (dopaminergic neurons) in an area of the midbrain called the substantia nigra which controls movement. This loss of dopaminergic neurons is associated with accumulation of a protein known as α-synuclein within neurons, which is thought to disrupt their function. Once around half of the dopaminergic neurons in the substantia nigra are lost, typically the clinical symptoms of Parkinson’s manifest, including slowness of movement, muscle stiffness and tremor. Parkinson’s can also cause a wide range of non-movement related symptoms including anxiety, sleep disturbance, gut symptoms, cognitive problems and dementia. There is growing scientific literature suggesting that inflammation contributes to the damage and loss of neurons in the brain in Parkinson’s. In particular, there is evidence that a complex of proteins called the NLRP3 inflammasome is activated within the inflammatory cells of the brain, called microglia, and this activation may be triggered by abnormal aggregates of α-synuclein protein. Activation of the NLRP3 inflammasome causes microglia to produce inflammatory molecules which are damaging to dopaminergic neurons, and may promote further α-synuclein aggregation, thus leading to a cyclical process of cell damage. Olatec believes that treatment with dapansutrile has the potential to inhibit the NLRP3 dependent neuroinflammatory process and in so doing arrest this cyclical process of cell damage thereby slowing the progression of the disease. About Dr. Caroline Williams-Gray, Principal Investigator Dr. Caroline Williams-Gray is a leading clinician scientist specializing in Parkinson’s disease and movement disorders. She studied medicine at Cambridge University and Oxford Clinical School, graduating in 2001, and gained her PhD from Cambridge University in 2008, thereafter training in neurology in Cambridge, Norwich and Queen Square, London. Dr. Williams-Gray leads the Cambridge Parkinson’s Disease Research Clinic. Dr. Williams-Gray’s work focuses on the theory that the immune system is a significant player in mediating the clinical variability of Parkinson’s disease and its progression; and in particular that peripheral immune activation plays a critical role through exacerbating microglial activation and neuronal damage in the brain. About Cure Parkinson’s Cure Parkinson’s, a UK-registered foundation, funds, facilitates and encourages research aiming to find a cure for Parkinson’s, with urgency, for people currently living with Parkinson’s. It was founded in 2005 by people living with Parkinson’s, who set out to find a cure. It focuses on research projects investigating disease-modifying therapies, with the potential to slow, stop or reverse the progression of Parkinson’s. Cure Parkinson’s partners with Van Andel Institute (VAI) and the John Black Charitable Foundation (JBCF) to fund an International Linked Clinical Trials (iLCT) initiative aiming to develop new, potentially disease-modifying Parkinson’s therapies. Together, they have directly funded, or secured funding from donors and fundraisers, for over £75 million supporting clinical trials searching for a cure for Parkinson’s and have pledged a total of USD $6.75 million to Parkinson’s research, over three years. Under its iLCT program, Cure Parkinson’s supports clinical trials based on a drug prioritization process conducted by a committee of world-leading experts. Over the last decade, the iLCT program has completed 13 trials and currently has 16 ongoing studies investigating 15 molecules. About Dapansutrile Dapansutrile (lab code: OLT1177 ® ) is an investigational small molecule, new chemical entity that specifically binds to and blocks NLRP3 (nucleotide-binding and oligomerization domain [NOD]‑, leucine rich repeat-, pyrin domain-containing 3), the sensor molecule integral in the formation of the NLRP3 inflammasome. Inflammasomes are multiprotein complexes involved in intracellular surveillance of danger signals that trigger an intense inflammatory response, via generation of bioactive IL-1β and IL-18 through caspase-1 activation. Dapansutrile has been shown to prevent the formation of the NLRP3 inflammasome, which in turn inhibits the production of IL-1β and IL‑18. Dapansutrile has been well tolerated and shown to improve clinical outcomes in patients with acute gout flare (see The Lancet Rheumatology ) and heart failure (see Journal of Cardiovascular Pharmacology ). Dapansutrile has also been observed to have anti-inflammatory properties and other promising activity in a broad spectrum of over 20 preclinical animal models including arthritis, asthma, acute myocardial infarction (AMI), heart failure, contact dermatitis, multiple sclerosis, melanoma, pancreatic and breast cancers, spinal cord injury (SCI), Parkinson’s and Alzheimer’s disease. For a complete list of Olatec’s original publications on dapansutrile in various preclinical and clinical disease areas, please refer to Olatec’s publication page, here . About Olatec Therapeutics, Inc. Olatec is a privately held, clinical-stage biopharmaceutical company developing a platform of oral NLRP3 inhibitors to treat and prevent a broad spectrum of acute and chronic inflammatory diseases known to be mediated by IL-1. Clinical trials include gout and diseases of aging such as type 2 diabetes, heart failure and cancer (see list of clinical trials to-date, here ). In addition to the lead compound, dapansutrile, Olatec’s platform of proprietary compounds includes approximately 40 analogues (OLT Analogues) being screened as viable drug candidates. A portfolio of intellectual property registrations protecting Olatec’s compounds consists of over 150 patents granted. Olatec’s drug development team is comprised of experienced management and international experts in translational medicine with unparalleled expertise in inflammation and immunology and has been involved in the discovery and development of first-line inflammation treatments in the market today. For more information, please visit http://www.olatec.com Disclaimer & Forward-looking Statement This press release is not an offer to sell and is not soliciting an offer to buy any equity interests in the Company. The information contained herein is being provided for information purposes only. The Company makes no express or implied representation or warranty as to the completeness of this information. Any forward-looking statements contained in this release are based on assumptions made by Olatec at the time this Press Release was prepared. Any forward-looking statement contained in this Press Release is subject to known and unknown risks, uncertainties and other factors that may be materially different from those contemplated in such forward-looking statements. All information with respect to industry data has been obtained from sources believed to be reliable and current, but the accuracy thereof cannot be guaranteed by the Company. Olatec does not undertake any obligation to update or revise the forward-looking statements contained in this Press Release to reflect events or circumstances occurring after the date this Press Release was prepared, or to reflect the occurrence of unanticipated events.