Acelex (polmacoxib) / CG Invites, Daewoong Pharma - LARVOL DELTA

Polypharmacology of carbonic anhydrase inhibitors and activators. (PubMed, Expert Opin Pharmacother) - "Several antiepileptics (topiramate, zonisamide, lacosamide, levetiracetam), some atypical antipsychotics (sulpiride, veralipride), celecoxib, polmacoxib, pazopanib, the antiulcer agent famotidine and compounds in clinical trials (epacadostat and PCI-27483) as antitumor agents significantly inhibit several CA isoforms of the 15 human ones, apart their action on several other targets...Polypharmacology involving CA inhibitors/CAAs are understood from the chemical, structural and pharmacological viewpoints. The many other drug targets with which these modulators of activity interact allow for de novo design of such agents for the management of multifactorial conditions in need of innovative drugs."

Journal • Review • CNS Disorders • Epilepsy • Genetic Disorders • Glaucoma • Obesity • Oncology • Ophthalmology

Polmacoxib 2mg in patients with mild to moderate idiopathic osteoarthritis of hip/knee-a randomized, double-anonymous study. (PubMed, Pain Manag) - "All patients were assessed with various pain measuring scales and recorded the scores at the end of weeks 3 and 6. The data for all the pain assessment scores were analyzed, and polmacoxib was found to be a non-inferior therapeutic agent compared to celecoxib in terms of safety and efficacy.(https://ctri.nic.in/CTRI/2022/05/042923)."

Journal • Cardiovascular • Gastrointestinal Disorder • Idiopathic Arthritis • Immunology • Osteoarthritis • Pain • Rheumatology

Perioperative Polmacoxib Reduce Opioid Consumption for Post Operative Pain After Rotator Cuff Tear. (clinicaltrials.gov) - P=N/A | N=150 | Recruiting | Sponsor: Eulji University Hospital

New trial • Pain

Polmacoxib: A Review of the Newer Non-steroidal Anti-inflammatory Drug in Osteoarthritis. (PubMed, Cureus) - "The dual mode of action exhibited by polmacoxib is expected to minimize adverse cardiovascular effects while achieving maximum effectiveness in inflamed osteoarthritic joints. This article aims to review the pharmacological properties, clinical efficacy, and safety data of polmacoxib in osteoarthritis."

Journal • Review • Cardiovascular • Gastrointestinal Disorder • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

CrystalGenomics to supply anti-osteoarthritis drug to Russia for $2 mn (The Korea Economic Daily) - "South Korea's first-generation biopharma venture company CrystalGenomics Inc. on Wednesday said it received a $2 million (2.6 billion won) order from a government-run Russian pharmaceutical company for its new anti-osteoarthritis drug Acelex, whose active ingredient is Polmacoxib. CrystalGenomics said it concluded a second supply contract worth $43.8 million with PharmArtis International and can earn up to $77.6 million in milestone (performance technology) fees based on additional sales."

Commercial • CNS Disorders • Osteoarthritis • Pain

Identification of new 4-(6-oxopyridazin-1-yl)benzenesulfonamides as multi-target anti-inflammatory agents targeting carbonic anhydrase, COX-2 and 5-LOX enzymes: synthesis, biological evaluations and modelling insights. (PubMed, J Enzyme Inhib Med Chem) - "First, the furanone heterocycle in the dual CA/COX-2 inhibitor Polmacoxib was replaced with the pyridazinone one...All of the disclosed pyridazinones were tested for inhibitory activities against 4 hCA isoforms (I, II, IX, and XII), as well as against COX-1/2, and 5-LOX. Furthermore, in vivo anti-inflammatory and analgesic effects of pyridazinones 7a and 7b were examined."

Journal • Pain

Phase III Study of CG100649 in Osteoarthritis Patients (clinicaltrials.gov) - P3 | N=362 | Completed | Sponsor: CrystalGenomics, Inc. | Unknown status ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology

Validation of the Claims-Based Definition for Knee Osteoarthritis in South Korea (ISPOR-EU 2022) - "The optimal definition included knee X-ray due to KOA, and specific medications (etoricoxib, polmacoxib, NSAIDs-Herbal, glucosamine, diacerein, chondroitin sulfate, or hyaluronate injection). Patients with KOA can be identified using a validated claims-based definition to generate real-world evidence in the NHI database."

Immunology • Osteoarthritis • Pain • Rheumatoid Arthritis • Rheumatology

Drug-Drug Interaction Study of "CG100650" in Healthy Volunteers (clinicaltrials.gov) - P1 | N=41 | Completed | Sponsor: CrystalGenomics, Inc. | Recruiting ➔ Completed

Trial completion

Daewoong readies to release Acelex generic (Korea Biomedical Review) - "Daewoong Pharmaceutical applied for a trademark, Acelcox (ingredient: polmacoxib), presumed to be a generic drug of Acelex, an osteoarthritis pain reliever....The name Acelcox is believed to be combined from the original drug “Acelex” and COX from 'COX-2'"

General generics event • CNS Disorders • Osteoarthritis • Pain

Population Pharmacokinetic and Pharmacodynamic Analysis of Polmacoxib in Healthy Volunteers and Patients With Osteoarthritis. (PubMed, Clin Ther) - "The current model accurately characterized the pharmacokinetic and pharmacodynamic properties of polmacoxib and could provide a basis for individualized drug therapy. (Clin Ther. 2021;XX:XXX-XXX)"

Clinical • Journal • PK/PD data • Immunology • Osteoarthritis • Pain • Rheumatology

Benzylic Aroylation of Toluenes Mediated by a LiN(SiMe)/Cs System. (PubMed, J Org Chem) - "Some challenging substrates with respect to benzylic deprotonations, such as fluoro and methoxy substituted toluenes, are selectively transformed to 2-aryl acetophenones. The value of benzylic deprotonation of 3-fluorotoluene is demonstrated by the synthesis of a key intermediate in the preparation of Polmacoxib."

Journal

Crystal Genomics ends phase 3 clinical trial in Russia for ’Acelex’… NDA planned [Google translation] (E-Today) - P3, N=250; NCT01765296; Sponsor: CrystalGenomics, Inc.; "Crystal Genomics announced on the 22nd that it has successfully completed phase 3 clinical trials of the osteoarthritis analgesic anti-inflammatory drug 'Acelex' (ingredient name Polmacoxib) for marketing approval in Russia....(The company explained that the treatment effect of non-inferiority was proven in all areas, including the Lequesne index) and the overall clinical evaluation and improvement scale (CGI-I)....A final clinical trial result report (CSR) for phase 3 clinical trials will be prepared and an application for permission to market Acelex (NDA) will be made to the Russian Food and Drug Administration."

Trial completion date • CNS Disorders • Osteoarthritis • Pain

Crystal Genomics completes NDA for ’Acelex’ in Brazil [Google translation] (Medical News) - "Crystal Genomics announced on the 17th that it has completed an application for permission (NDA) for the sale of a new drug,'Acelex (ingredient name Polmacoxib)', an anti-osteoarthritis analgesic, to the Brazilian Food and Drug Administration (ANVISA)....'When a new drug is approved, marketing and distribution companies in Brazil have already been selected, so it will serve as a cash cow according to sales.'"

Non-US regulatory • CNS Disorders • Osteoarthritis • Pain

CrystalGenomics announces positive results from phase 2b osteoarthritis study of CG100649 (PRNewswire) - P2b, N=132; CG100649-2-02; Throughout the study, both of the CG100649 treatment groups demonstrated non-inferiority compared to Celebrex on all primary and secondary outcome measures; There were no drug-related serious AEs in either of the CG100649 treatment groups or in the Celebrex treatment group

P2b data • Pain

A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis. (PubMed, Clin Orthop Surg) - "The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered safe for long-term use based on this relatively small scale of study in a Korean population. More importantly, the results of this study showed that polmacoxib has the potential to be used as a pain relief drug with reduced gastrointestinal side effects compared to traditional nonsteroidal anti-inflammatory drugs for OA."

Clinical • Journal • P1 data • P2 data • P3 data • Biosimilar • Osteoarthritis • Pain

CrystalGenomics partners with TR-Pharm for Acelex commercialization in Turkey and MENA (PRNewswire) - "CrystalGenomics, Inc. has announced that it has signed a License and Supply Agreement with TR-Pharm for the commercialization of Acelex® (polmacoxib) in Turkey and the Middle East and North Africa (MENA) region....Based on the current projections, it is anticipated that the cumulative sales of Acelex will reach USD 253 million in the licensed region over the course of the term of the Agreement."

Licensing / partnership • Sales projection • Pain

An unusual case of colon perforation with multiple transmural ulcers after use of polmacoxib and everolimus in a metastatic breast cancer patient: A case report. (PubMed, Ann Coloproctol) - "Intestinal perforation has not been reported previously as a complication of everolimus, and perforation of the lower intestinal tract caused by a selective COX2 inhibitor is extremely rare. We present here a case of colon perforation that occurred after use of polmacoxib in a metastatic breast cancer patient who had been treated with everolimus for the preceding six months."

Clinical • Journal

An update on drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors. (PubMed, Expert Opin Drug Metab Toxicol) - "An update on their drug-drug interactions is presented here considering these main therapeutic areas and drugs: glaucoma (acetazolamide, methazolamide, dichlorophenamide, dorzolamide and brinzolamide); epilepsy/obesity (sulthiame, topiramate and zonisamide); arthritis/inflammation (celecoxib and polmacoxib) and hypoxic tumors (SLC-0111).Areas covered...Fewer interactions were reported for the anti-glaucoma agents, whereas synergistic combinations of celecoxib with antibiotics or SLC-0111 with various antitumor drugs were extensively investigated.Expert opinion. Drug interactions involving CAIs may be used both for monitoring the clinical efficacy of these agents when co-administered with other drugs but also for better controlling some diseases, such as hypoxic tumors, case for which the combination of CAIs with other anticancer agents (histone deacetylase inhibitors, alkylating agents, antimetabolite nucleosides, angiogenesis inhibitors and immune check point..."

Journal

Crystal Genomics, Daehwa win patent for patch-form arthritis drug (Korea Biomedical Review) - "Crystal Genomics and Daehwa Pharmaceutical said they have registered a patent for their patch-form Acelex, a degenerative arthritis treatment. The two companies will hold the patent until it expires on March 22, 2038."

Patent

Crystal Genomics acquires US patent for 'Aselex', a new drug for osteoarthritis treatment (The Korea Economic Daily) - "Innovative drug development company specialized crystal...Genomics...(United States Patent registered for the crystal forms and compositions') of the osteoarthritis treatment drug...The registered patent is a US patent for the crystalline forms and compositions of the next generation osteoarthritis treatment drug Asselex raw chemicals. The period is until June 22, 2037."

Patent