{"product_id":"domagrozumab-pf-06252616-10mg","title":"Domagrozumab (PF-06252616) 10mg","description":"\u003cp data-pm-slice=\"1 1 []\"\u003e\u003cspan style=\"color: rgb(255, 42, 0);\"\u003eDue to the nature of this product being a monoclonal antibody and thus must be manufactured and stored under stringent quality standards, order fulfillment requires additional processing time. Please allow 2–3 weeks for production, plus shipping time, to ensure we deliver a product that meets our quality and purity specifications.\u003c\/span\u003e\u003c\/p\u003e\n\u003cp data-pm-slice=\"1 1 []\"\u003e\u003cstrong\u003e\u003cspan style=\"color: rgb(255, 42, 0);\"\u003e                                         \u003cspan style=\"text-decoration: underline;\"\u003eNOT \u003c\/span\u003e\u003c\/span\u003e\u003c\/strong\u003e\u003cspan style=\"text-decoration: underline;\"\u003e\u003cstrong\u003e\u003cspan style=\"color: rgb(255, 42, 0); text-decoration: underline;\"\u003eFOR HUMAN CONSUMPTION\u003c\/span\u003e\u003c\/strong\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003cp data-end=\"681\" data-start=\"180\"\u003e\u003cstrong data-end=\"210\" data-start=\"180\"\u003eDomagrozumab PF-06252616)\u003c\/strong\u003e is a \u003cstrong data-end=\"254\" data-start=\"216\"\u003ehumanized IgG1 monoclonal antibody\u003c\/strong\u003e that \u003cstrong data-end=\"293\" data-start=\"260\"\u003eneutralizes myostatin (GDF-8)\u003c\/strong\u003e—a TGF-β–superfamily ligand that acts as a \u003cstrong data-end=\"393\" data-start=\"336\"\u003edominant negative regulator of skeletal muscle growth\u003c\/strong\u003e. The therapeutic premise was that sustained myostatin blockade would increase \u003cstrong data-end=\"492\" data-start=\"472\"\u003elean muscle mass\u003c\/strong\u003e, and ideally improve \u003cstrong data-end=\"539\" data-start=\"514\"\u003estrength and function\u003c\/strong\u003e in diseases such as \u003cstrong data-end=\"597\" data-start=\"560\"\u003eDuchenne muscular dystrophy (DMD)\u003c\/strong\u003e and certain limb-girdle muscular dystrophies. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003cp data-end=\"865\" data-start=\"683\"\u003e\u003cstrong data-end=\"705\" data-start=\"683\"\u003eRegulatory status:\u003c\/strong\u003e investigational; \u003cstrong data-end=\"747\" data-start=\"723\"\u003enot FDA\/EMA-approved\u003c\/strong\u003e. Pfizer \u003cstrong data-end=\"770\" data-start=\"756\"\u003eterminated\u003c\/strong\u003e key DMD clinical studies after Phase 2 efficacy failure. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003chr data-end=\"870\" data-start=\"867\"\u003e\n\u003ch2 data-end=\"932\" data-start=\"872\"\u003e2) Target biology: myostatin\u003c\/h2\u003e\n\u003cp data-end=\"1245\" data-start=\"933\"\u003eMyostatin signals via \u003cstrong data-end=\"1002\" data-start=\"955\"\u003eactivin type II receptors (ActRIIA\/ActRIIB)\u003c\/strong\u003e to activate \u003cstrong data-end=\"1026\" data-start=\"1015\"\u003eSMAD2\/3\u003c\/strong\u003e pathways that suppress muscle hypertrophy. Blocking myostatin is a high-confidence way to increase muscle size in many models, but across human neuromuscular disease programs a consistent translational lesson has been:\u003c\/p\u003e\n\u003cblockquote data-end=\"1469\" data-start=\"1247\"\u003e\n\u003cp data-end=\"1469\" data-start=\"1249\"\u003e\u003cstrong data-end=\"1321\" data-start=\"1249\"\u003eLean mass gains do not reliably convert into functional improvements\u003c\/strong\u003e, especially when muscle is compromised by fibrosis, fatty infiltration, denervation, or ongoing degeneration. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003c\/blockquote\u003e\n\u003chr data-end=\"1474\" data-start=\"1471\"\u003e\n\u003ch2 data-end=\"1539\" data-start=\"1476\"\u003e3) Proposed benefits under investigation (evidence-weighted)\u003c\/h2\u003e\n\u003cdiv class=\"TyagGW_tableContainer\"\u003e\n\u003cdiv class=\"group TyagGW_tableWrapper flex flex-col-reverse w-fit\" tabindex=\"-1\"\u003e\n\u003ctable class=\"w-fit min-w-(--thread-content-width)\" data-end=\"2264\" data-start=\"1540\"\u003e\n\u003cthead data-end=\"1596\" data-start=\"1540\"\u003e\n\u003ctr data-end=\"1596\" data-start=\"1540\"\u003e\n\u003cth data-col-size=\"sm\" data-end=\"1549\" data-start=\"1540\"\u003eDomain\u003c\/th\u003e\n\u003cth data-col-size=\"md\" data-end=\"1569\" data-start=\"1549\"\u003eWhat was expected\u003c\/th\u003e\n\u003cth data-col-size=\"lg\" data-end=\"1596\" data-start=\"1569\"\u003eWhat the data supported\u003c\/th\u003e\n\u003c\/tr\u003e\n\u003c\/thead\u003e\n\u003ctbody data-end=\"2264\" data-start=\"1611\"\u003e\n\u003ctr data-end=\"1811\" data-start=\"1611\"\u003e\n\u003ctd data-col-size=\"sm\" data-end=\"1639\" data-start=\"1611\"\u003eLean mass \/ muscle volume\u003c\/td\u003e\n\u003ctd data-end=\"1682\" data-start=\"1639\" data-col-size=\"md\"\u003e↑ muscle size \/ lean mass as a PD signal\u003c\/td\u003e\n\u003ctd data-end=\"1811\" data-start=\"1682\" data-col-size=\"lg\"\u003e\n\u003cstrong data-end=\"1713\" data-start=\"1684\"\u003eNon-significant increases\u003c\/strong\u003e in muscle volume vs placebo were observed in DMD Phase 2. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-end=\"2049\" data-start=\"1812\"\u003e\n\u003ctd data-col-size=\"sm\" data-end=\"1843\" data-start=\"1812\"\u003eFunctional performance (DMD)\u003c\/td\u003e\n\u003ctd data-end=\"1904\" data-start=\"1843\" data-col-size=\"md\"\u003eimproved mobility and timed function (e.g., 4-stair climb)\u003c\/td\u003e\n\u003ctd data-end=\"2049\" data-start=\"1904\" data-col-size=\"lg\"\u003e\n\u003cstrong data-end=\"1934\" data-start=\"1906\"\u003ePrimary endpoint not met\u003c\/strong\u003e; overall efficacy measures did not support a significant treatment effect. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr data-end=\"2264\" data-start=\"2050\"\u003e\n\u003ctd data-col-size=\"sm\" data-end=\"2080\" data-start=\"2050\"\u003eMuscle disease modification\u003c\/td\u003e\n\u003ctd data-end=\"2121\" data-start=\"2080\" data-col-size=\"md\"\u003eslowing decline \/ improving NSAA, etc.\u003c\/td\u003e\n\u003ctd data-end=\"2264\" data-start=\"2121\" data-col-size=\"lg\"\u003eReviews note \u003cstrong data-end=\"2146\" data-start=\"2136\"\u003etrends\u003c\/strong\u003e in some measures, but not robust efficacy sufficient to continue development. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\n\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003chr data-end=\"2269\" data-start=\"2266\"\u003e\n\u003ch2 data-end=\"2306\" data-start=\"2271\"\u003e4) Molecular mechanism of action\u003c\/h2\u003e\n\u003ch3 data-end=\"2356\" data-start=\"2308\"\u003e4.1 Pharmacodynamics (ligand neutralization)\u003c\/h3\u003e\n\u003cul data-end=\"2557\" data-start=\"2357\"\u003e\n\u003cli data-end=\"2557\" data-start=\"2357\"\u003e\n\u003cp data-end=\"2557\" data-start=\"2359\"\u003eDomagrozumab \u003cstrong data-end=\"2403\" data-start=\"2372\"\u003ebinds circulating myostatin\u003c\/strong\u003e, preventing receptor engagement and reducing SMAD2\/3 signaling downstream (conceptual for all anti-myostatin mAbs). \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003ch3 data-end=\"2599\" data-start=\"2559\"\u003e4.2 Target engagement and PD signals\u003c\/h3\u003e\n\u003cp data-end=\"2853\" data-start=\"2600\"\u003eIn first-in-human work, domagrozumab showed \u003cstrong data-end=\"2663\" data-start=\"2644\"\u003etypical IgG1 PK\u003c\/strong\u003e and evidence of \u003cstrong data-end=\"2701\" data-start=\"2680\"\u003etarget engagement\u003c\/strong\u003e, with a myostatin-modulation signal that \u003cstrong data-end=\"2784\" data-start=\"2743\"\u003eplateaued around the 20 mg\/kg IV dose\u003c\/strong\u003e (in that study’s PD readouts). \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003chr data-end=\"2858\" data-start=\"2855\"\u003e\n\u003ch2 data-end=\"2917\" data-start=\"2860\"\u003e5) Pharmacokinetics and administration \u003c\/h2\u003e\n\u003cp data-end=\"3006\" data-start=\"2918\"\u003eIn healthy-subject studies, domagrozumab demonstrated \u003cstrong data-end=\"3005\" data-start=\"2972\"\u003etypical IgG1 pharmacokinetics\u003c\/strong\u003e:\u003c\/p\u003e\n\u003cul data-end=\"3159\" data-start=\"3007\"\u003e\n\u003cli data-end=\"3041\" data-start=\"3007\"\u003e\n\u003cp data-end=\"3041\" data-start=\"3009\"\u003eslow absorption after SC dosing,\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"3059\" data-start=\"3042\"\u003e\n\u003cp data-end=\"3059\" data-start=\"3044\"\u003eslow clearance,\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"3089\" data-start=\"3060\"\u003e\n\u003cp data-end=\"3089\" data-start=\"3062\"\u003elow volume of distribution,\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"3159\" data-start=\"3090\"\u003e\n\u003cp data-end=\"3159\" data-start=\"3092\"\u003elong half-life (mAb-typical). \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp data-end=\"3366\" data-start=\"3161\"\u003eIn the DMD Phase 2 program, dosing was by \u003cstrong data-end=\"3219\" data-start=\"3203\"\u003eIV infusions\u003c\/strong\u003e at multiple ascending dose levels (5, 20, 40 mg\/kg) with measured serum concentrations increasing with dose. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003chr data-end=\"3371\" data-start=\"3368\"\u003e\n\u003ch2 data-end=\"3409\" data-start=\"3373\"\u003e6) Clinical evidence \u003c\/h2\u003e\n\u003ch3 data-end=\"3495\" data-start=\"3411\"\u003e6.1 Duchenne muscular dystrophy: Phase 2 randomized trial + open-label extension\u003c\/h3\u003e\n\u003cp data-end=\"3634\" data-start=\"3496\"\u003eA Phase 2 randomized, double-blind trial in ambulatory boys with DMD evaluated domagrozumab vs placebo with a primary functional endpoint:\u003c\/p\u003e\n\u003cul data-end=\"4042\" data-start=\"3636\"\u003e\n\u003cli data-end=\"3711\" data-start=\"3636\"\u003e\n\u003cp data-end=\"3711\" data-start=\"3638\"\u003e\u003cstrong data-end=\"3659\" data-start=\"3638\"\u003ePrimary endpoint:\u003c\/strong\u003e change in \u003cstrong data-end=\"3698\" data-start=\"3670\"\u003e4-stair climb (4SC) time\u003c\/strong\u003e at week 49\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"3819\" data-start=\"3712\"\u003e\n\u003cp data-end=\"3819\" data-start=\"3714\"\u003e\u003cstrong data-end=\"3725\" data-start=\"3714\"\u003eResult:\u003c\/strong\u003e \u003cstrong data-end=\"3754\" data-start=\"3726\"\u003eprimary endpoint not met\u003c\/strong\u003e; efficacy measures did not show a significant treatment effect\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"3913\" data-start=\"3820\"\u003e\n\u003cp data-end=\"3913\" data-start=\"3822\"\u003e\u003cstrong data-end=\"3853\" data-start=\"3822\"\u003eBody composition \/ imaging:\u003c\/strong\u003e \u003cstrong data-end=\"3873\" data-start=\"3854\"\u003enon-significant\u003c\/strong\u003e increases in muscle volume vs placebo\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"4042\" data-start=\"3914\"\u003e\n\u003cp data-end=\"4042\" data-start=\"3916\"\u003e\u003cstrong data-end=\"3927\" data-start=\"3916\"\u003eSafety:\u003c\/strong\u003e generally safe and well tolerated; most AEs mild and not treatment related \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003cp data-end=\"4174\" data-start=\"4044\"\u003ePfizer subsequently announced termination of the DMD Phase 2 and its open-label extension. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003ch3 data-end=\"4255\" data-start=\"4176\"\u003e6.2 Limb-girdle muscular dystrophy (LGMD R9\/2I; FKRP-related): Phase Ib\/IIa\u003c\/h3\u003e\n\u003cp data-end=\"4482\" data-start=\"4256\"\u003eAn open-label multiple ascending-dose study in \u003cstrong data-end=\"4330\" data-start=\"4303\"\u003eFKRP-related LGMD R9\/2I\u003c\/strong\u003e concluded that domagrozumab was \u003cstrong data-end=\"4371\" data-start=\"4363\"\u003esafe\u003c\/strong\u003e, but there was \u003cstrong data-end=\"4441\" data-start=\"4387\"\u003eno clear evidence of clinically meaningful benefit\u003c\/strong\u003e. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003chr data-end=\"4487\" data-start=\"4484\"\u003e\n\u003ch2 data-end=\"4543\" data-start=\"4489\"\u003e7) Safety and tolerability \u003c\/h2\u003e\n\u003ch3 data-end=\"4567\" data-start=\"4545\"\u003e7.1 Common\/overall\u003c\/h3\u003e\n\u003cp data-end=\"4733\" data-start=\"4568\"\u003eIn DMD Phase 2, most participants experienced at least one AE, typically \u003cstrong data-end=\"4649\" data-start=\"4641\"\u003emild\u003c\/strong\u003e and often not considered treatment-related. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003ch3 data-end=\"4811\" data-start=\"4735\"\u003e7.2 Serious adverse events and immunogenicity (from public CSR synopses)\u003c\/h3\u003e\n\u003cp data-end=\"5110\" data-start=\"4812\"\u003ePfizer’s public clinical study report synopsis for the Phase 2 DMD study describes treatment-related SAEs including (examples listed): \u003cstrong data-end=\"4972\" data-start=\"4947\"\u003efemoral neck fracture\u003c\/strong\u003e, \u003cstrong data-end=\"4985\" data-start=\"4974\"\u003eanxiety\u003c\/strong\u003e, and \u003cstrong data-end=\"5013\" data-start=\"4991\"\u003etroponin increased\u003c\/strong\u003e, with one discontinuation due to SAE anxiety (40 mg\/kg). \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003cp data-end=\"5259\" data-start=\"5112\"\u003e\u003cem data-end=\"5259\" data-start=\"5112\"\u003e(CSR synopses are helpful for safety granularity, but they are not substitutes for a full regulatory label because the product was not approved.)\u003c\/em\u003e\u003c\/p\u003e\n\u003chr data-end=\"5264\" data-start=\"5261\"\u003e\n\u003ch2 data-end=\"5316\" data-start=\"5266\"\u003e8) Development outcome and regulatory landscape\u003c\/h2\u003e\n\u003cp data-end=\"5552\" data-start=\"5317\"\u003eDomagrozumab remained \u003cstrong data-end=\"5358\" data-start=\"5339\"\u003einvestigational\u003c\/strong\u003e and Pfizer \u003cstrong data-end=\"5386\" data-start=\"5370\"\u003ediscontinued\u003c\/strong\u003e DMD development after failure to meet the Phase 2 primary endpoint, terminating both the main study and open-label extension. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003chr data-end=\"5557\" data-start=\"5554\"\u003e\n\u003ch2 data-end=\"5616\" data-start=\"5559\"\u003e9) Scientific synthesis\u003c\/h2\u003e\n\u003cp data-end=\"5684\" data-start=\"5617\"\u003eDomagrozumab fits a recurring pattern seen in myostatin inhibition:\u003c\/p\u003e\n\u003col data-end=\"5874\" data-start=\"5685\"\u003e\n\u003cli data-end=\"5755\" data-start=\"5685\"\u003e\n\u003cp data-end=\"5755\" data-start=\"5688\"\u003e\u003cstrong data-end=\"5748\" data-start=\"5688\"\u003eTarget engagement and some mass\/volume signals can occur\u003c\/strong\u003e, but\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"5874\" data-start=\"5756\"\u003e\n\u003cp data-end=\"5874\" data-start=\"5759\"\u003e\u003cstrong data-end=\"5800\" data-start=\"5759\"\u003eFunctional endpoints are hard to move\u003c\/strong\u003e in progressive dystrophies where structural pathology limits translation.\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ol\u003e\n\u003cp data-end=\"6130\" data-start=\"5876\"\u003eThis does not invalidate myostatin biology; it indicates that \u003cstrong data-end=\"6050\" data-start=\"5938\"\u003edisease context, endpoint choice, and combination strategies (rehab\/training, antifibrotics, gene therapies)\u003c\/strong\u003e may be essential for functional impact. \u003cspan data-state=\"closed\" class=\"\"\u003e\u003c\/span\u003e\u003c\/p\u003e\n\u003chr data-end=\"6135\" data-start=\"6132\"\u003e\n\u003ch2 data-end=\"6204\" data-start=\"6137\"\u003e10) Future directions \u003c\/h2\u003e\n\u003cp data-end=\"6279\" data-start=\"6205\"\u003eIf an anti-myostatin approach were pursued now, the “must haves” would be:\u003c\/p\u003e\n\u003cul data-end=\"6745\" data-start=\"6280\"\u003e\n\u003cli data-end=\"6398\" data-start=\"6280\"\u003e\n\u003cp data-end=\"6398\" data-start=\"6282\"\u003e\u003cstrong data-end=\"6313\" data-start=\"6282\"\u003eFunction-first trial design\u003c\/strong\u003e (power, stair climb, sit-to-stand, VO₂peak, ADLs) plus standardized rehab\/training\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"6496\" data-start=\"6399\"\u003e\n\u003cp data-end=\"6496\" data-start=\"6401\"\u003e\u003cstrong data-end=\"6419\" data-start=\"6401\"\u003eMuscle quality\u003c\/strong\u003e metrics (MRI volume + intramuscular fat + strength per CSA), not DXA alone\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"6670\" data-start=\"6497\"\u003e\n\u003cp data-end=\"6670\" data-start=\"6499\"\u003e\u003cstrong data-end=\"6535\" data-start=\"6499\"\u003eEarlier or different indications\u003c\/strong\u003e where muscle is salvageable (frailty, GLP-1–associated lean loss, post-hospital deconditioning) rather than advanced dystrophy alone\u003c\/p\u003e\n\u003c\/li\u003e\n\u003cli data-end=\"6745\" data-start=\"6671\"\u003e\n\u003cp data-end=\"6745\" data-start=\"6673\"\u003eClear \u003cstrong data-end=\"6706\" data-start=\"6679\"\u003ePK\/PD target engagement\u003c\/strong\u003e thresholds tied to functional outcomes\u003c\/p\u003e\n\u003c\/li\u003e\n\u003c\/ul\u003e","brand":"RCpeptides","offers":[{"title":"Default Title","offer_id":52684838240594,"sku":null,"price":4000.0,"currency_code":"EUR","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/1048\/0956\/2450\/files\/Domagrozumab_10mg.png?v=1770834783","url":"https:\/\/sciencepeptideslab.com\/products\/domagrozumab-pf-06252616-10mg","provider":"Science Peptides Lab","version":"1.0","type":"link"}