{"id":5735,"date":"2025-11-08T20:39:13","date_gmt":"2025-11-09T03:39:13","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=5735"},"modified":"2025-11-08T20:39:17","modified_gmt":"2025-11-09T03:39:17","slug":"comparison-of-baff-april-inhibitors-2","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2025\/11\/08\/5735\/comparison-of-baff-april-inhibitors-2\/","title":{"rendered":"COMPARISON OF BAFF \/ APRIL INHIBITORS \u2013 2"},"content":{"rendered":"

\"\"<\/a>Shortly after posting our last blog on tacicepts, new data was published in the NEJM on the pivotal Phase 3 trial of atacicept.\u00a0 This publication by Lafayette et al. provides results from an IA of the ongoing ORIGIN-3 trial.[1] <\/a>\u00a0We updated our table with this new information that centers on reduction of proteinuria, UCPR and hematuria.<\/p>\n

The authors do not provide information on the GFR effects of atacicept claiming that this data has to stay blinded until the 2-yr endpoint. This strikes us as strange, because S-creatinine and GFR are measured frequently in every patient enrolled, and interim GFR trends could have been provided without breaking the blind for the final analysis.<\/p>\n

The efficacy results are impressive; we learned that pathologic Gd-IgA1 levels, specific autoantibodies and circulating immune complexes were reduced.\u00a0 We don\u2019t know whether these laboratory improvements will ultimately lead to less deposition of Igs in the glomerular mesangium, with corresponding clinical benefit. These lab changes could eventually become early biomarkers of clinical efficacy if confirmed by GFR and possibly kidney biopsy.<\/p>\n

\"\"<\/a>
atacicept ORIGIN-3 Interim data<\/figcaption><\/figure>\n

Reduction in the concentrations of IgG, IgA and IgM was not of a magnitude to affect immune response against infections; it takes a much greater drop in immunoglobulin levels to become problematic in this regard.\u00a0 This was shown in the tacicept and FcRn inhibitor trials as well.\u00a0 FcRn inhibitors reduce IgG levels by up to 70% and are not associated with a noticeable increase in infections.<\/p>\n

\"\"<\/a>
Tacicepts Comparison<\/figcaption><\/figure>\n

The higher frequency of injection site reactions in the atacicept arm, however, was surprising.\u00a0 Unfortunately, the article did not provide much detail except for making a boilerplate statement that most AEs were \u2018mild in severity\u2019.\u00a0 We feel this deserves a closer look.<\/p>\n

The authors state that the study participants were \u2018representative of the general population of patients with IgA nephropathy\u2019.\u00a0 Is that really true? \u00a0White, Asian and Latino patients were enrolled but almost no Blacks. \u00a0This is concerning, as a 2023 epidemiology study shows that IgAN is an issue in black patients as well, but here they were underrepresented.[2]<\/a><\/p>\n

\"\"<\/a>
IgAN demographics \/ US<\/figcaption><\/figure>\n

Please check back here periodically as more data become available.<\/p>\n

ABBREVIATIONS<\/strong>
\nAPRIL\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 a proliferation-inducing ligand
\nBAFF\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0B-cell activating factor
\nCKD\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 chronic kidney disease
\neGFR\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 estimated glomerular filtration rate
\nGdIgA\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0galactose-deficient IgA
\nIA\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 interim analysis
\nIgAN\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 immunoglobulin A nephropathy
\nPBO\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0placebo
\nUPCR\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a0urine protein to creatinine ratio<\/p>\n

REFERENCES
\n<\/strong>[1] <\/a>Lafayette R.\u00a0 A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy.\u00a0 NEJM DOI: 10.1056\/NEJMoa2510198
\n[2]<\/a> Kiryluk K.\u00a0 Global Incidence of IgA Nephropathy by Race and Ethnicity: A Systematic Review.\u00a0 KIDNEY360 4: 1112, 2023<\/p>\n","protected":false},"excerpt":{"rendered":"

Shortly after posting our last blog on tacicepts, new data was published in the NEJM on the pivotal Phase 3 trial of atacicept.\u00a0 This publication by Lafayette et al. provides results from an IA of the ongoing ORIGIN-3 trial.[1] \u00a0We updated our table with this new information that centers on Continue reading COMPARISON OF BAFF \/ APRIL INHIBITORS \u2013 2<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":5716,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[227,3,18],"tags":[1271,2209,2529,2531,2532,2533,2408,2530,1583,2211,2212,2536,2210,2229,2535,2527,2208,2230,2534,2226],"class_list":["post-5735","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","category-the_viewpoint","tag-allphase-pharma-consulting","tag-atacicept","tag-baff-april-inhibitors","tag-comparison-of-phase-3-trials","tag-competition-in-igan","tag-efficacy-comparison-of-tacicepts","tag-fcrn-inhibitors","tag-fda-endpoints","tag-harald-reinhart","tag-iga-nephropathy","tag-igan","tag-origin-trial","tag-povetacicept","tag-proteinuria","tag-rainier-trial","tag-remegen","tag-telitacicept","tag-upcr","tag-vera-pharma","tag-vertex"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/tacicept-SLIDER2.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-1uv","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":5697,"url":"https:\/\/allphasepharma.com\/dir\/2025\/11\/03\/5697\/comparison-of-baff-april-inhibitors\/","url_meta":{"origin":5735,"position":0},"title":"COMPARISON OF BAFF \/ APRIL INHIBITORS","author":"Harald","date":"November 3, 2025","format":false,"excerpt":"First, a reminder where the name \u2018Berger\u2019s disease\u2019 or Morbus Berger comes from.\u00a0It was Jean Berger, a French pathologist and doctor, who initially identified IgA deposits on the glomeruli of nephritic patients.\u00a0 This was not so long ago; his publication (in French) dates from 1968.[1] Now the race is heating\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/Povetacicept-PK-e1762226541807.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/Povetacicept-PK-e1762226541807.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/Povetacicept-PK-e1762226541807.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":5771,"url":"https:\/\/allphasepharma.com\/dir\/2025\/11\/17\/5771\/tacicepts-vying-for-your-attention\/","url_meta":{"origin":5735,"position":1},"title":"TACICEPTS VYING FOR YOUR ATTENTION","author":"Harald","date":"November 17, 2025","format":false,"excerpt":"Two posters on tacicepts caught our eyes. 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This is an interim look at Phase 1b study data reporting on 17 IgAN patients treated for 48 weeks with a dose of 80 mg and 30 patients\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/TACICEPTS-VYING-FOR-ATTENTION-scaled.jpg?fit=1200%2C338&ssl=1&resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/TACICEPTS-VYING-FOR-ATTENTION-scaled.jpg?fit=1200%2C338&ssl=1&resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/TACICEPTS-VYING-FOR-ATTENTION-scaled.jpg?fit=1200%2C338&ssl=1&resize=525%2C300 1.5x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/TACICEPTS-VYING-FOR-ATTENTION-scaled.jpg?fit=1200%2C338&ssl=1&resize=700%2C400 2x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/TACICEPTS-VYING-FOR-ATTENTION-scaled.jpg?fit=1200%2C338&ssl=1&resize=1050%2C600 3x"},"classes":[]},{"id":4416,"url":"https:\/\/allphasepharma.com\/dir\/2025\/05\/30\/4416\/baff-april-inhibitors-homing-in-on-igan\/","url_meta":{"origin":5735,"position":2},"title":"BAFF \/ APRIL Inhibitors Homing in on IgAN","author":"Harald","date":"May 30, 2025","format":false,"excerpt":"Today we discuss the group of BAFF\/APRIL inhibitors, specifically the three TACI mAb constructs that are currently in development. 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So far, consistent clinical success has been seen only in IgA nephropathy (IgAN), with\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/05\/HR-BLOG-BAFF-APRIL.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/05\/HR-BLOG-BAFF-APRIL.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/05\/HR-BLOG-BAFF-APRIL.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":6362,"url":"https:\/\/allphasepharma.com\/dir\/2026\/03\/31\/6362\/igan-therapeutics-the-race-is-on\/","url_meta":{"origin":5735,"position":3},"title":"IgAN Therapeutics – The Race is On","author":"Harald","date":"March 31, 2026","format":false,"excerpt":"Is there a new trend in the journal world: \u00a0publication of interim analysis (IA) results? 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