Delving into the Latest Updates on HMR-4052 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Radotermin

+ [1]

Target

Growth factor receptor

Mechanism

Unspecified growth factor receptor modulators

Therapeutic Areas

Skin and Musculoskeletal DiseasesUrogenital DiseasesOther Diseases

Active Indication

Bone DiseasesErectile DysfunctionWounds and Injuries

Inactive Indication-

Originator Organization

Sanofi

Active Organization

Sanofi

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 13829484

Source: *****

The use of bioactive agents combined with osteoconductive scaffolds for the regeneration of periodontal intrabony defects has been the subject of intensive research in the past 20 years. Most studies reported that such agents, used in different concentrations, doses and combined with various scaffolds, might promote periodontal tissue regeneration, but evidence for the most effective combination of such agents is lacking. The objective of this study 13 was to rank the different combinations of recombinant human-derived growth and differentiation factors with/without scaffold biomaterial in the treatment of periodontal intrabony defects, through network meta-analysis of pre-clinical studies. The systematic review and network meta-analysis protocol was registered on the PROSPERO Systematic Review database with reference number: CRD42021213673. Relevant published articles were obtained after searching five electronic databases. A specific search strategy was followed by using keywords related to intrabony defects, regenerative materials, scaffolds and recombinant factors, and animal studies. All pre-clinical studies used for periodontal regeneration were included. The primary outcomes were: regeneration of junctional epithelium (mm), new cementum, connective tissue attachment, percentage of new bone formation (%), bone area (mm² ), bone volume density (g/cm³ ) and bone height (mm) data was extracted. The analysis was carried out using network meta-analysis methods, that is illustrating network plots, contribution plots, predictive and confidence interval plot, surface under the cumulative ranking (SUCRA), multidimensional scale ranking and net funnel plots using STATA IC statistical software. An SYRCLE's tool for assessing risk of bias was used for reporting risk of bias among individual studies. A total of N = 24 for qualitative and N = 21 studies for quantitative analysis published till 2020 were included. The cumulative total number of animals included in the control and test groups were N = 162 and N = 339, respectively. The duration of the study was between 3 and 102 weeks rhBMP-2 ranked higher in SUCRA as the agent associated with the best performance for bone volume density. rhGDF-5/TCP ranked best in the bone area (mm2), rhPDGF-BB/Equine ranked best in bone height (mm), rhBMP-2 ranked best in the percentage of new bone fill, rhBMP-2/ACS ranked best in new cementum formation, and rhGDF-5/b- TCP/PLGA ranked best in connective tissue attachment and junctional epithelium. There were no adverse effects identified in the literature that could affect the different outcomes for regeneration in intrabony defects. Various recombinant factors are effective in promoting the regeneration of both soft and hard tissue supporting structures of the periodontium. However, when considering different outcomes, different agents, associated or not with biomaterials, ranked best. Keeping into account the limited transferability of results from animal studies to the clinical setting, the choice of the most appropriate formulation of bioactive agents may depend on clinical needs and purpose.

01 Nov 2021·Journal of Tissue Engineering and Regenerative MedicineQ2 · ENGINEERING & TECHNOLOGY

Regenerative benefits of using growth factors in treatment of periodontal defects: A systematic review and meta‐analysis with Trial Sequential Analysis on preclinical studies

Q2 · ENGINEERING & TECHNOLOGY

Review

Author: Akbari, Solmaz ; Shamshiri, Ahmad Reza ; Asl roosta, Hoori ; Farimani, Zeinab ; Bohlouli, Mahboubeh

The ultimate goal in periodontal treatments is to achieve a functional and anatomical regeneration of the lost tissues. Numerous studies have in some way illustrated the beneficial effects of biologic modifiers in this process, yet they are subject to a rather large degree of diversity in their results. Thanks to the promising outcomes of bioengineering techniques in the field of periodontal regeneration, this systematic review aims to evaluate the effect of various biologic modifiers used in periodontal defects of animal models. Electronic databases (Medline, Scopus, Embase, Web of Science, and Google Scholar) were searched (March 2010-December 2020) for every study that used biomolecules for regeneration of periodontal osseous defects in animal models. Regenerated bone height or area, new cementum, new connective tissues, new regenerated periodontal ligament and the dimensions of epithelial attachment (either in mm/mm² or percentage) were the investigated outcomes. The risk of bias of the included studies was assessed using the SYRCLE tool. In closing, there was a meta-analysis carried out on the outcomes of interest. Trial Sequential Analysis was also carried out to figure out the power of meta-analytic outcomes. From 1995 studies which were found in the initial search, 34 studies were included in this review, and 20 of them were selected for the meta-analysis. The eligible studies were categorized according to the morphology of the experimental periodontal defects as one-, two-, and three-wall intrabony defects; furcation defects, and recession-type defects. The most studied biomolecules were rhFGF-2, rhGDF-5, platelet-derived growth factor, bone morphogenetic protein-2, and enamel matrix derivative (EMD). Based on the meta-analysis findings, combined application of biomolecules with regenerative treatments could improve new bone and cementum formation near 1 mm when compared to the control groups in one, two and three-wall intrabony defect models (p < 0.001). In furcation grade II defect, the addition of biomolecules was observed to enhance bone area gain and cementum height regeneration up to almost 2 mm (p < 0.001). Trial Sequential Analysis results confirmed the significant effect in the aforementioned meta-analyses. In cases of the buccal recession model, the application of rhFGF-2 and rhGDF-5 decreased the dimension of epithelial attachments besides regenerative advantages on bone and cementum formation, but EMD deposition exerted no inhibitory effect on epithelial down-growth. Application of biologic modifiers especially FGF-2 and GDF-5, could positively improve the regeneration of periodontal tissues, particularly cementum and bone in animal models. Trial Sequential Analysis confirmed the results but the power of the evidences was high just in some subgroup meta-analyses, like bone and cementum regeneration in furcation grade II model and cementum regeneration in one-wall intrabony defects. The outcomes of this study can potentially endow clinicians with guidelines for the appropriate application of growth factors in periodontal regenerative therapies.

01 Oct 2021·Biotechnology JournalQ3 · ENGINEERING & TECHNOLOGY

Blockage of undesirable endocytosis of recombinant human growth/differentiation factor‐5 in Chinese hamster ovary cell cultures requires heparin analogs with specific chain lengths

Q3 · ENGINEERING & TECHNOLOGY

Article

Author: Lee, Gyun Min ; Kim, Mi Gyeom

AbstractCell surface heparan sulfate proteoglycan (HSPG)‐mediated endocytosis lowers the yield of recombinant human bone morphogenetic proteins (rhBMPs), such as rhBMP‐2 and rhBMP‐4, from Chinese hamster ovary (CHO) cell cultures. Exogenous recombinant human growth/differentiation factor‐5 (rhGDF‐5), a member of the BMP family, bound to cell surface HSPGs and was actively internalized into CHO cells. Knockdown of heparan sulfate (HS) synthesis enzymes in CHO cells revealed that the chain length and N‐sulfation of HS affected the binding of rhGDF‐5 to HSPGs and subsequent rhGDF‐5 internalization. To increase product yield by minimizing rhGDF‐5 internalization in recombinant CHO (rCHO) cell cultures, heparin, and dextran sulfate (DS) of various polysaccharide chain lengths, which are structural analogs of HS, were examined for blockage of rhGDF‐5 internalization. Heparin fragments of four monosaccharides (MW of 1.2 kDa) and DS (MW of 15 kDa) did not inhibit rhGDF‐5 internalization whereas unfractionated heparin and DS of 200 kDa could significantly inhibit it. Compared to the control cultures, supplementation with unfractionated heparin or DS of 200 kDa at 1 g L‐1 resulted in more than a 10‐fold increase in the maximum rhGDF‐5 concentration. Taken together, the supplementation of structural HS analogs improved rhGDF‐5 production in rCHO cell cultures by inhibiting rhGDF‐5 internalization.

100 Deals associated with HMR-4052

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Bone Diseases	Phase 2	-	Sanofi	-
Erectile Dysfunction	Phase 2	-	Sanofi	-
Wounds and Injuries	Phase 2	-	Sanofi	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01124006 (CTgov)	Phase 2	Intervertebral Disc Degeneration	24	rhGDF-5 (Intradiscal rhGDF-5 (1.0mg))	aznuckblnd(ukczbgtdut) = ozrsslusyu wjigtgxjvd (mioclwxiej, fvnqzbhjdy - adktulsxjz) View more	-	24 Feb 2016
				Trehalose+Glycine+rhGDF-5 (Placebo)	hquzflqplc(hmuwawydud) = ebapsxvybo smpepkaruo (zwwbnvofnf, unmuyshltt - yejoitndsz) View more
NCT01158924 (CTgov)	Phase 1/2	-	40	rhGDF-5 (Intradiscal rhGDF-5 (1.0mg))	bfzltyzvkf(glpnhhuofb) = vqracbrmme qpmblgqdkv (kvkvujsaca, xzenisiqdm - qfamcwtsoo) View more	-	27 Jan 2016
				rhGDF-5 (Intradiscal rhGDF-5 (2.0mg))	bfzltyzvkf(glpnhhuofb) = zogmrzjihx qpmblgqdkv (kvkvujsaca, grbnsawocs - wtemvudycz) View more
NCT00813813 (CTgov)	Phase 1/2	Intervertebral Disc Degeneration	32	rhGDF-5 (Intradiscal rhGDF-5 (0.25mg))	neubrauaxm(kvmiqlylyl) = niziconbzn bdrvjhiklx (jmfqxvxwev, gshxbbkamc - rzswhsssxg) View more	-	27 Jan 2016
				rhGDF-5 (Intradiscal rhGDF-5 (1.0mg))	neubrauaxm(kvmiqlylyl) = slpkrxqlyr bdrvjhiklx (jmfqxvxwev, okefpfzwwc - xxktgkdnfd) View more
NCT01182337 (CTgov)	Phase 1/2	-	31	Vehicle Control (Vehicle Control)	nikdlaezle(elytsjvxwt) = bstypfqbmg pjsszzwagr (gtzocqkknb, jsmcuxshxe - rgpjliqeyn) View more	-	27 Jan 2016
				Intradiscal rhGDF-5 (Intradiscal rhGDF-5)	ecysdpchwt(qycwnykxqd) = qnrmmbqdvw qdtncqkaez (wdcvyllrdd, ployainzkw - wjpwlgwklr) View more