"We are very encouraged by multiple clear signals of treatment benefit in this study - the achievement of the primary endpoint in all 12 patients that completed the study, the achievement of disease remission in more than 50% of patients, and the achievement of at least a five-point reduction in disease activity in 14 of 15 patients," said
"The clinical response in IgG4-RD patients treated with XmAb5871 is very impressive and reinforces my belief that this is a promising potential therapy," said Dr.
Final Efficacy Data:
Twelve of 15 patients (80%) completed the study and all 12 achieved the primary endpoint of at least a two-point reduction in the IgG4-RD RI on Day 169. None of the 12 required corticosteroids (CS) after month two. Eight patients achieved remission (IgG4-RD RI of 0 and no CS after two months) and the other four achieved IgG4-RD RI scores of ≤4 at Day 169. Fourteen of 15 patients (93%) achieved a decrease of ≥ 5 in the IgG4-RD RI. One patient had been on baseline CS for two years (15 mg/day) and was able to discontinue CS within two months. Four others received CS at the start of the trial and tapered off within two months.
Safety and Tolerability Data:
XmAb5871 was well tolerated. Three patients had minor, transient GI side-effects during the first infusion; all completed the study. Two serious adverse events (SAEs) unrelated to XmAb5871 were observed in one patient, pneumonia and recurrence of pneumonia due to non-compliance (patient completed study). Three patients discontinued the study, as disclosed previously. One discontinued patient was atypical with laryngeal involvement only who did not respond to XmAb5871 or to subsequent rituximab. A second patient responded, but flared at 12 weeks and did not respond to subsequent rituximab therapy. The third patient responded but developed infusion-related symptoms including transient rash and arthralgias following the fifth infusion.
Plasmablasts were reduced 70-80% from baseline and B cells were reduced 40-55% from baseline, with decreases occurring within the first two weeks.
The presentation will be available on the 'Investors' page of
Based on these results,
About the Clinical Trial
IgG4-RD patients with active disease defined by an IgG4-RD Responder Index (RI) of ≥3 were administered XmAb5871 (5 mg/kg intravenously) every 14 days for 12 doses. The primary outcome measure was the proportion of patients on Day 169 with a decrease in the IgG4-RD RI of ≥2 points compared to baseline.
Fifteen patients were enrolled in the study, having a median IgG4-RD RI of 12 (range 2-30) with active inflammatory disease in a median of five organ systems (1-10). The organs most commonly affected were lymph nodes (73% of patients), submandibular glands (60%), parotid glands (53%), and lacrimal glands (47%). Five patients (33%) had kidney involvement, four (27%) had lung findings and three each (20%) had orbital lesions, nasal cavity involvement or heart/pericardium findings.
Conference Call and Webcast:
The live call may be accessed by dialing (877) 359-9508 for domestic callers or (224) 357-2393 for international callers, and referencing conference ID number: 99272433. A live webcast of the conference call will be available online from the investor relations section of the company's website at www.xencor.com. The webcast will be archived on the company's website for 30 days.
XmAb®5871 is a first-in-class monoclonal antibody that targets CD19 with its variable domain and that uses Xencor's XmAb immune inhibitor Fc domain to target FcγRIIb, a receptor that inhibits B-cell function. XmAb5871 is the first drug candidate that Xencor is aware of that targets FcγRIIb inhibition. Xencor has demonstrated in multiple animal models and in initial human clinical trials that XmAb5871 inhibits B-cell function without destroying these important immune cells, and demonstrated promising treatment effect in patients with rheumatoid arthritis, as well as ex vivo results showing inhibition of systemic lupus erythematosus (SLE) patient B-cell activation and humoral immunity. XmAb5871 is currently in clinical development for IgG4-RD and SLE.
About IgG4-Related Disease
IgG4-Related Disease (IgG4-RD) is a rare fibro-inflammatory autoimmune disorder that is estimated to impact up to 40,000 patients in the
FcγRIIb (IIb), also called CD32b, is a receptor for Fc domains on B cells and other immune cells. When engaged, the IIb receptor blocks immune activation pathways and traffics bound soluble antigens out of circulation.
Xencor is a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune diseases, asthma and allergic diseases and cancer. Currently, 11 candidates engineered with Xencor's XmAb® technology are in clinical development internally and with partners. Xencor's internal programs include: XmAb®5871 in Phase 2 development for the treatment of IgG4-Related Disease, and also for the treatment of Systemic Lupus Erythematosus; XmAb®7195 in Phase 1 development for the treatment of asthma and allergic diseases; XmAb®14045 in Phase 1 development for acute myeloid leukemia; XmAb®13676 in Phase 1 development for B-cell malignancies; XmAb®18087 in pre-clinical development for the treatment of neuroendocrine tumors; and XmAb®20717 in pre-clinical development for the treatment of multiple cancers. Xencor's XmAb antibody engineering technology enables small changes to the structure of monoclonal antibodies resulting in new mechanisms of therapeutic action. Xencor partners include Novartis, Amgen, MorphoSys, Merck, CSL/Janssen, Alexion and Boehringer Ingelheim. For more information, please visit www.xencor.com.
Forward Looking Statements:
Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of applicable securities laws, including the quotation from
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