A Phase 1, Single-dose, Non-Randomized, Open-label, Parallel-group Study to Assess the Pharmacokinetics and Safety of Lenabasum in Subjects with Hepatic Impairment Compared with Matched Healthy Controls

Start Date27 Jul 2020

Sponsor / Collaborator

Corbus Pharmaceuticals Holdings, Inc.

[+1]

100 Clinical Results associated with Ajulemic acid

100 Translational Medicine associated with Ajulemic acid

100 Patents (Medical) associated with Ajulemic acid

126

Literatures (Medical) associated with Ajulemic acid

01 Jan 2025·JID innovations : skin science from molecules to population health

Long-Term Safety and Efficacy of Lenabasum, a Cannabinoid Receptor Type 2 Agonist, in Patients with Dermatomyositis with Refractory Skin Disease: Follow-Up Data from a 3-Year Open-Label Extension Study

Article

Author: Faden, Daniella Forman ; White, Barbara ; Xie, Lillian ; Poroye, Joy ; Stone, Caroline J. ; Werth, Victoria P. ; Lopes Almeida Gomes, Lais ; Stone, Caroline J ; Ahuja, Geeta ; Feng, Rui ; Werth, Victoria P

OBJECTIVES:

This study utilizes data from the open-label extension (OLE) phase of the lenabasum phase 2 trial and additional post-OLE follow-up data. Key aims include evaluating the drug's long-term effectiveness and assessing disease manifestation recurrence.

METHODS:

The phase 2 lenabasum trial enrolled patients with treatment-resistant, skin-predominant DM. The OLE consisted of a 3-year period during which 20 patients were on the drug for the entire duration, with assessments every 8 weeks to evaluate drug safety and efficacy. Subsequently, a follow-up retrospective chart review was performed on patients who completed the OLE as well as on control subjects with DM who did not participate in the lenabasum trial.

RESULTS:

By week 68, patients exhibited reductions in Cutaneous Dermatomyositis Disease Area and Severity Index activity score (-21.8), Patient Skin Activity Visual Analog Scale (-3.0), and Skindex-29 (-28.0) from OLE baseline. After OLE, 58.3% maintained stable disease, significantly higher than controls (P = .035), with 41.7% not experiencing flares compared with 91.6% of controls. In addition, 50% of patients reported sustained pruritus improvement.

CONCLUSIONS:

Data from OLE and subsequent follow-up periods demonstrate lenabasum's efficacy in maintaining disease stability, reducing flares, and improving DM symptoms, suggesting that it is a promising option for patients with treatment-resistant skin-predominant DM.

TRIAL REGISTRATION:

This study was registered at clinicaltrials.gov, with NCT02466243. Study registration was first submitted on June 2, 2015.

01 Dec 2023·The Journal of investigative dermatology

Validation of Cutaneous Dermatomyositis Disease Area and Severity Index Activity Score and Other Efficacy Outcomes as Measures of Skin Disease in Dermatomyositis in the Lenabasum Phase 3 Trial

Article

Author: Kleitsch, Julianne ; White, Barbara ; Pandya, Rachita ; Werth, Victoria P ; Dan, Joshua

In the past decade, there have been six industry-sponsored phase 3 trials in adult patients with dermatomyositis (DM), primarily focusing on improving muscle weakness. However, skin disease is a cardinal manifestation of DM. This study evaluated the sensitivity of Cutaneous Dermatomyositis Disease Area and Severity Index Activity score, Cutaneous Dermatomyositis Activity Investigator Global Assessment, Total Improvement Score, and other outcome measures used in DM clinical trials to detect improvement in DM skin disease activity. Data analyzed from the lenabasum phase 3 trial in DM showed that improvement in Cutaneous Dermatomyositis Disease Area and Severity Index Activity score increased proportionately with the degree of patient- or physician-reported improvement in skin disease, consistently measuring improvement when clinically meaningful improvement was reported at weeks 16-52. In contrast, Cutaneous Dermatomyositis Activity Investigator Global Assessment measured little change from baseline with reported no improvement in skin disease but also a similar change from baseline with slight improvement. No Skindex-29+3 subscale performed well at reflecting increasing degrees of improvement in skin disease. Extramuscular Global Assessment and Total Improvement Score generally showed increasing levels of improvement as the degree of patient- and physician-reported improvement in skin disease increased, but these are composite measures and are not specific to improvement in DM skin disease. To measure clinically meaningful improvement in skin disease in a DM trial, Cutaneous Dermatomyositis Disease Area and Severity Index Activity score is the more sensitive outcome measure across time points.

01 Sep 2023·Arthritis & rheumatology (Hoboken, N.J.)

Efficacy and Safety of Lenabasum, a Cannabinoid Type 2 Receptor Agonist, in a Phase 3 Randomized Trial in Diffuse Cutaneous Systemic Sclerosis.

Article

Author: Jun, Jae-Bum ; Khanna, Dinesh ; White, Barbara ; Spiera, Robert ; Kafaja, Suzanne ; Distler, Oliver ; Denton, Christopher P ; Kuwana, Masataka ; de Vries-Bouwstra, Jeska ; Levy, Yair ; Sandorfi, Nora ; Furst, Daniel E ; Lee, Eun Bong ; Dgetluck, Nancy ; Jankowski, Tomasz ; Simms, Robert W ; Litinsky, Irena ; Stevens, Wendy ; Dinh, Quinn ; Mayes, Maureen ; Chung, Lorina ; Matucci-Cerinic, Marco ; Leszcyzński, Piotr ; Steen, Virginia ; Bloom, Bradley J ; Hummers, Laura ; Hsu, Vivien ; Gordon, Jessica ; Frech, Tracy M ; Finzel, Stephanie ; Constantine, Scott

OBJECTIVE:

This phase 3 study was undertaken to investigate the efficacy and safety of lenabasum, a cannabinoid type 2 receptor agonist, in patients with diffuse cutaneous systemic sclerosis (dcSSc).

METHODS:

A multinational double-blind study was conducted in 365 dcSSc patients who were randomized and dosed 1:1:1 with lenabasum 20 mg, lenabasum 5 mg, or placebo, each twice daily and added to background treatments, including immunosuppressive therapies (IST).

RESULTS:

The primary end point, the American College of Rheumatology combined response index in dcSSc (CRISS) at week 52 for lenabasum 20 mg twice a day versus placebo, was not met, with CRISS score of 0.888 versus 0.887 (P = 0.4972, using mixed models repeated measures [MMRM]). The change in the modified Rodnan skin thickness score (MRSS) at week 52 for lenabasum 20 mg twice a day versus placebo was -6.7 versus -8.1 (P = 0.1183, using MMRM). Prespecified analyses showed higher CRISS scores, greater improvement in MRSS, and lower decline in forced vital capacity in patients on background mycophenolate and those who were taking IST for ≤1 year. No deaths or excess in serious or severe adverse events related to lenabasum were observed.

CONCLUSION:

A benefit of lenabasum in dcSSc was not demonstrated. Most patients were treated with background IST, and treatment with mycophenolate mofetil in particular was associated with better outcomes. These findings support the use of IST in the treatment of dcSSc and highlight the challenge of demonstrating a treatment effect when investigational treatment is added to standard of care IST. These findings have relevance to trial design in SSc, as well as to clinical care.

News (Medical) associated with Ajulemic acid

19 Jul 2023

·www.sciencedaily.com

Towards new antibiotics with the first artificial synthesis of tanzawaic acid b

Drug-resistant bacteria represent a major threat to public health worldwide, and scientists are constantly searching for novel antibiotic compounds. In a recent study, a research team achieved the first artificial synthesis of tanzawaic acid B, a promising antibiotic drug candidate, on gram scale. Their findings can make synthetic tanzawaic acids widely available, paving the way for the discovery of new drugs. The discovery of antibiotics in 1928 was a major turning point in the history of medicine. For the first time since the dawn of human civilization, doctors had gained access to an extremely powerful and effective tool to fight against a wide variety of bacterial infections. Today, bacterial diseases that were previously a death sentence can be cured, and infections following surgery or chemotherapy can be prevented or treated more effectively. Unfortunately, the worldwide use (and abuse) of antibiotics led to the emergence of drug-resistant bacterial strains. Over time, bacteria that could normally be killed by a given antibiotic produced mutant offspring immune to it. These mutant strains are a major threat to public health, and the only safe course of action is to develop new antibiotic compounds. Against this backdrop, a research team including Professor Isamu Shiina, Assistant Professor Takatsugu Murata and Mr. Hisazumi Tsutsui from the Tokyo University of Science (TUS) in Japan has now achieved a major breakthrough in the synthesis of new antibiotics. As reported in their paper published in ACS Omega in July 2023, the team achieved the first-ever gram-scale synthesis of tanzawaic acid B, which can serve as a candidate for the discovery of new drugs. But what is tanzawaic acid B? In 1997, Professor Daisuke Uemura and colleagues working in the Tanzawa area of Japan isolated a series of organic polyketide compounds from the fungus Penicillium citrinum. These compounds were grouped together into what we now call the "tanzawaic" acid family, containing dozens of members ranging from A to Z1. In particular, tanzawaic acid B has attracted the most attention as it shares a common core structure with many tanzawaic acids, meaning that an artificial synthesis method for tanzawaic acid B could readily lead to synthesis methods for the rest. However, synthesizing tanzawaic acid B from scratch is a challenging endeavor. The tanzawaic acids share a polysubstituted octalin skeleton -- a structure composed of 10 carbon atoms in a tight pattern with multiple chemical groups at specific locations. The researchers synthesized this skeleton by utilizing a chain-like molecule that they had synthesized in a previous study. Then, by leveraging a carefully controlled intramolecular Diels-Alder reaction, they made these chains preferentially "fold" into the desired octalin skeleton. The next challenge was to precisely modify the octalin skeleton in multiple steps to produce tanzawaic acid B. As octalin has eight carbon atoms that can participate in stereochemical reactions, any desired substitution effectively competes with 255 other possible arrangements. To tackle this issue, the researchers employed asymmetric alkylation and asymmetric Mukaiyama aldol reaction, which enabled them to produce the desired polysubstituted octalin compound tanzawaic acid B on gram scale. Overall, this new synthesis technique could play a key role in the development of antibiotic drugs based on tanzawaic acids. Excited about the outcome of the study, Prof. Shiina comments: "For more than 25 years since its discovery, the total synthesis of tanzawaic acid B had not been realized, until now. The present synthesis method will hopefully lead to the creation of various compounds for pharmaceuticals in the future, including new antibiotic candidates for multidrug-resistant bacteria." With a continuous, large-scale supply of tanzawaic acids, researchers will soon be able to test their interesting biological activities, including antibacterial, antimalarial, and antifungal properties. "Further improvements to the synthesis of tanzawaic acid B are currently underway, along with the investigations of its biological activity and synthetic analogs," concludes Prof. Shiina.

11 Jul 2023

·www.sciencedaily.com

Drug precursor biosynthesis hinges on carrier-mediated ring formation

The entire biosynthetic pathway of actinopyridazone has been unveiled, revealing that an unprecedented carrier protein-mediated ring-forming step is key to its synthesis. The entire biosynthetic pathway of actinopyridazone has been unveiled, revealing that an unprecedented carrier protein-mediated ring-forming step is key to its synthesis. Nitrogen-nitrogen bond-containing cyclic compounds such as pyrazole, triazole, pyridazine and many others are critical building blocks for a variety of medicinal compounds, both natural and synthetic. The biosynthesis of some of these compounds hinges on the formation of nitrogen-nitrogen (N-N) single bonds between amino acids. However, the mechanisms by which a diversity of compounds is possible is poorly understood. Dr. Kenichi Matsuda and Professor Toshiyuki Wakimoto at Hokkaido University led a team to elucidate the biosynthetic pathway of actinopyridazinone, an N-N bond-containing cyclic compound that is an important scaffold for synthetic drugs. Their findings were published in the journal Angewandte Chemie International Edition. "Actinopyridazinone is produced by Streptomyces, a genus of bacteria that is the source of the majority of antibiotics of natural origin," Wakimoto explains. "It is the first natural compound known to possess a dihydropyridazinone ring. This ring is also known as a 'wonder nucleus,' as it has been extensively studied as a precursor for a wide range of drugs." In previous work, the team used bioinformatics to identify a group of gene sequences that are potentially involved in the biosynthesis of natural products that contain N-N bonds, and from these genome sequences, they discovered the novel class of compounds called actinopyradizones. With a series of genetic and biochemical experiments, they were also able to unveil the first steps in the pathway; in this study, they focused on understanding how the dihydropyridazone ring is formed. The gene cluster apy is the biosynthetic gene cluster associated with actinopyradizone synthesis. It contains 17 potential genes; knockout studies indicated that ten of these -- apy1, apy2, apy3, apy4, apy6, apy8, apy9, apy10, apy11 and apy13 -- were necessary for actinopyradizone synthesis. Biochemical analyses of the knockouts allowed the team to deduce that Apy3, an AMP-dependent synthetase/ligase, Apy4, a serine hydrolase, and Apy6, a carrier protein-rhodanese fusion, were the key proteins responsible for the formation of the dihydropyridazone ring. "Apy6 functions as a carrier molecule; and Apy3 loads the intermediate compound onto Apy6," Matsuda elaborates. "Apy4 then catalyses the removal of an acetyl group (-COCH3); the resulting molecule is unstable and spontaneously reacts to form a dihydropyridazone ring. The most notable feature of actinopyridazone biosynthesis is the unprecedented carrier protein-mediated machinery for dihydropyridazinone formation." Matsuda said that this study is the first description of the biosynthetic pathway for actinopyradizone, and is only the second study to report the enzyme-dependent biosynthesis of a N-N bond-containing ring structure. The first such compound is piperazic acid, whose biosynthetic pathways are completely unrelated; hence, this study has also highlighted that the biosynthetic pathways of N-N bond-containing cyclic compounds are very diverse.

Clinical Result

30 May 2023

·www.businesswire.com

KND Labs Named 2023 NASC MVP Supplier of the Year

LAKEWOOD, Colo.--( BUSINESS WIRE )--KND Labs is pleased to announce the company has been named National Animal Supplement Council’s (NASC) MVP Supplier of the Year in 2023 — KND Labs’ second consecutive year receiving this recognition . MVP Supplier of the Year is awarded by the NASC Board of Directors each year during the organization’s annual member conference as a way to showcase the supplier most beneficial to its members in the last year. The award is presented based on a series of performance metrics including delivery of excellence in products and services; continuing industry education through webinars and presentations; and support and service to individual companies. “KND Labs is thrilled and honored by this continued recognition as the premier supplier of CBD ingredients for pet products,” said KND Labs President Nich Wilson. “As the authority in animal supplements, this award from NASC underscores KND Labs’ commitment to our pet industry partners and our goal of being the most compliant certified supplier of bulk hemp-derived ingredients.” The award comes on the heels of the groundbreaking release of a study conducted by NASC on the tolerability of CBD in dogs. Pet brands and veterinarians alike continue to promote the use of CBD oil in products for dogs, cats and other animals based on their endocannabinoid systems. The study, which has been submitted for peer review, shows the tolerability of broad spectrum cannabidiol (CBD), broad spectrum CBD with cannabigerol (CBG) and broad-spectrum CBD with cannabidiolic acid (CBDA) in healthy male and female dogs when given a daily dose for 90 consecutive days. “Part of what makes this study unique is the data from support from the NASC’s Adverse Event Reporting System (NAERS™) which is the most advanced system of post market surveillance in the world,” said Bill Bookout, President of NASC, in announcing the study result. “Through this system, NASC members enter their products, ingredients, and administration recommendations into the NAERS database along with the number of units in each container provided to customers. These collective data are processed by algorithms in the system and Adverse Events, both serious and non-serious, can be compared and analyzed per million administrations.” The discovery further supports the use of therapeutic CBD in healthy dogs, which often is used in response to animals with seizures, anxiety, pain, skin issues, and other physical and neurological issues. “Partnering with a trustworthy CBD supply chain partner is critical for producers of pet supplements and other pet industry products,” said KND Labs Manager of Sales, Courtlandt Pennell. “Having now earned the NASC MVP supplier award for two years running, KND Labs has shown time and again our commitment to compliance and quality for our partners in the pet industry and across all the industries we serve.” In addition to its NASC supplier status, KND Labs is also NSF, cGMP 111 and 117, euGMP Effci ISO 9001, Kosher-certified and is certified as an API (Active Pharmaceutical Ingredients) manufacturer for the pharmaceutical industry and for OTC applications. About KND Labs KND Labs is a leading manufacturer of hemp-derived ingredients, extracting quality bulk ingredients for brands and manufacturers of both human and pet products. Focused on certification and compliance in the CBD market, KND is a preferred NASC supplier, EFFCI eGMP, 21 CFR PART 117 cGMP, 21 CFR Part 111 cGMP, ISO 9001:2105 certified, API certified, NSF certified, USDA Organic certified and Kosher certified. KND is also an active member of the European Industrial Hemp Association (EIHA) and an FDA Drug Establishment. With two state-of-the-art facilities in Lakewood, Colo. and Arvada, Colo., KND Labs produces hemp-derived cannabinoids such as CBD, CBG, and other hemp-derived cannabinoids in powdered isolate form, distillate oil form and liquid or powder water-soluble form. Learn more at kndlabs.com .

100 Deals associated with Ajulemic acid

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Lupus Erythematosus, Discoid	Phase 3	US	Corbus Pharmaceuticals Holdings, Inc.	30 Jan 2022
Dermatomyositis	Phase 3	US	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018
Dermatomyositis	Phase 3	JP	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018
Dermatomyositis	Phase 3	BG	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018
Dermatomyositis	Phase 3	CA	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018
Dermatomyositis	Phase 3	CZ	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018
Dermatomyositis	Phase 3	DE	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018
Dermatomyositis	Phase 3	HU	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018
Dermatomyositis	Phase 3	IT	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018
Dermatomyositis	Phase 3	PL	Corbus Pharmaceuticals Holdings, Inc.	17 Dec 2018

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02466243 (phase 2 lenabasum trial, Pubmed \| JID Innov)	Phase 2	cytokines	20	Lenabasum	phhebtoayt(kejeskklqq) = vezeeechxp vquyylfzeu (kjieiehzfy ) View more	Positive	01 Jan 2025
				Lenabasum (Control subjects with DM)	phhebtoayt(kejeskklqq) = mfwzrfcxtc vquyylfzeu (kjieiehzfy )
NCT02466243 (phase 2 lenabasum trial \| JBT101-DM-001, CTgov)	Phase 2	Dermatomyositis	22	Placebo (Placebo)	zefqtacvmq(qehytyvpfr) = izdupcndsv uwieapneow (qymlwfmiov, tlxshibpfl - pccnywxnhq) View more	-	19 Jan 2023
				JBT-101 (JBT-101)	okcxijyngs(zjjkvfmhhk) = lsfhpsqddz hlpffatnrf (bqnucqjcsq, kezhteexgp - vgbklzwwvb) View more
NCT03451045 (CTgov)	Phase 2	Cystic Fibrosis	447	Lenabasum 20 mg (Lenabasum 20 mg BID)	ytipvhvzzx(tsdnvpcyuj) = ikyemkiucd rhzpwldvqg (gaajdcvgek, zdczytbund - jswboupsdd) View more	-	18 Jan 2023
				Lenabasum 5 mg (Lenabasum 5 mg BID)	ytipvhvzzx(tsdnvpcyuj) = ctxveryzam rhzpwldvqg (gaajdcvgek, gallbfkkzd - wrpmffwvvr) View more
NCT03093402 (CTgov)	Phase 2	Systemic Lupus Erythematosus	109	JBT-101 (High: JBT-101 20mg/20mg)	efnumshexm(djpufywcyi) = xdeqmrjiqh mojjtptlfk (zscnapwuqn, lfmfongtgj - mngsfwysts) View more	-	18 Nov 2022
				JBT-101 (Medium: JBT-101 20mg/Placebo)	efnumshexm(djpufywcyi) = pzulbcryoa mojjtptlfk (zscnapwuqn, kgajsnncfv - scywskzcci) View more
DETERMINE (EULAR2022)	Phase 3	Dermatomyositis	175	Lenabasum 20mg BID	zjyewnzzmo(oebvzpdojz) = fiidwjcsrq mbabyrgtwg (npxjsrsetk, 7.76)	Negative	01 Jun 2022
				Placebo BID	zjyewnzzmo(oebvzpdojz) = jwjsbbfecx mbabyrgtwg (npxjsrsetk, 8.88)
NCT02466243 (JBT101-DM-001, EULAR2021)	Phase 2	Skin Diseases	22	Lenabasum 20 mg BID	upvdkawgwi(fxoapqltog) = All OLE subjects experienced at least 1 adverse event (AE), with 118 AEs during the OLE through Dec 2020. Most AEs were mild (n = 111, 94%), with 2 severe AEs (fatigue and metastatic prostate cancer) considered unrelated to lenabasum. AEs occurring in ≥ 3/20 OLE subjects were: URI (n = 5); fatigue (n = 4); nausea (n = 3); common cold (n = 3); UTI (n = 3); and DM flare (n = 3). No serious AEs related to lenabasum have been reported in this OLE to date. No subject discontinued the OLE because of an AE related to lenabasum. jihtoyvazx (fntcfiyrfd ) View more	Positive	02 Jun 2021
Phase 3 Trial of Lenabasum (EULAR2021)	Phase 3	Scleroderma, Diffuse CB2	363	Lenabasum 5 mg	pwkezfaqvd(zvfsnvlcrp) = njehkzwqjk hdcgnfqqfl (ywqlitijzu, (6.91))	-	02 Jun 2021
				Lenabasum 20 mg	pwkezfaqvd(zvfsnvlcrp) = xxtpcsnilt hdcgnfqqfl (ywqlitijzu, (6.91))
NCT02465450 (Pubmed \| J Cyst Fibros) Manual	Phase 2	Cystic Fibrosis	89	lenabasum	ediqubnkwe(xfcdvulers) = hthjeqettt qzowltxvcm (xmfmdrpvso ) View more	Positive	01 Jan 2021
				Placebo	ediqubnkwe(xfcdvulers) = oqypbljodo qzowltxvcm (xmfmdrpvso ) View more
NCT03398837 \| NCT02465437 (ACR2020)	Phase 2/3	COVID-19 \| Scleroderma, Diffuse	385	Lenabasum 20 mg BID	kyocygwydt(fnnfrlymky) = Four/385 (0.11%) participants suffered a COVID-19 adverse event (AEs), including one serious AE (SAE) xodccgotol (nmvpwtzylu )	Positive	08 Nov 2020
NCT03398837 (RESOLVE-1, GlobeNewswire) Manual	Phase 3	Scleroderma, Systemic	365	Lenabasum	cnhybdnlki(mxcextjczo) = tckgmobhqi igdsaljnjz (cocwtbbbmz ) View more	Negative	09 Sep 2020
				Placebo	cnhybdnlki(mxcextjczo) = dvuovoljkr igdsaljnjz (cocwtbbbmz ) View more

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