{"id":5771,"date":"2025-11-17T21:14:43","date_gmt":"2025-11-18T04:14:43","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=5771"},"modified":"2025-12-10T20:04:36","modified_gmt":"2025-12-11T03:04:36","slug":"tacicepts-vying-for-your-attention","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2025\/11\/17\/5771\/tacicepts-vying-for-your-attention\/","title":{"rendered":"TACICEPTS VYING FOR YOUR ATTENTION"},"content":{"rendered":"\n
\"\"<\/a><\/figure>\n\n\n\n

Two posters on tacicepts caught our eyes.<\/p>\n\n\n\n

First is the Tumlin publication on povetacicept, an oral presentation in the “Late-Breaking Research” session. 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 with a 240 mg dose; both arms are dosed SC q4w.[1]<\/a><\/p>\n\n\n\n

Given the small patient cohort, open study design and absence of a placebo arm, this is just a first glimpse at efficacy. As it was a late-breaker, nobody bothered to check for typos either.<\/p>\n\n\n\n

We are told that the GFR ‘stabilized’; UPCR, hematuria and Gd-IgA1 levels were reduced. These early data confirm what we already know about the class of BAFF\/APRIL inhibitors; namely, that povetacicept does well on all accounts.  It is too early to make any quantitative comparisons or claims.  No need to update our tacicept comparison table from a prior blog yet, as we are only tracking pivotal Phase 3 trials. We are puzzled, however, by the lack of a dose response despite the 3-fold difference in dosing regimens.<\/p>\n\n\n\n

We interpret these data as a signal or trend in the right direction.<\/p>\n\n\n\n

Second, the Lafayette poster is about the atacicept ORIGIN-3 study, labeled correctly a “High-Impact Clinical Trial”.[2]<\/a>  Here, dosing was150 mg SC weekly.  The 36-wk results are indeed impressive but wait, where are the new data?  Could this be a duplicate publication?<\/p>\n\n\n

\n
\"\"<\/a>
ORIGIN-3 IA – From: Lafayette JASN<\/figcaption><\/figure>\n<\/div>\n\n\n

A recent NEJM article by Lafayette and the Vera team provided outcome information on the same population, now with graphs stacked vertically [3]<\/a>:<\/p>\n\n\n

\n
\"\"<\/a>
ORIGIN-3 IA – From: Lafayette NEJM<\/figcaption><\/figure>\n<\/div>\n\n\n

While the data for UPCR and Gd-IgA1 reductions are identical, we noticed some subtle changes to the hematuria graph: atacicept no longer comes out at -81.0% but at -82.1%, while hematuria in the placebo arm now shows a  -19.4% reduction, somewhat less than the -20.7% quoted in the (earlier) NEJM article.  Of note, the odds ratios are nevertheless unchanged.<\/p>\n\n\n\n

Both graphs and publications deal with the same IA of 203 patients (atacicept N=106; placebo N=97) at Week 36.  Why this difference?<\/p>\n\n\n\n

Usually, we are not sticklers about a 1-2% deviation in results from an IA, and neither should you be. Data correction of a single patient outcome may account for such small discrepancies. What seems like a duplicate publication is probably meant to be an update, a correction of sorts, to a secondary endpoint.<\/p>\n\n\n\n

This is, however, more than a routine IA. This data set with UPCR reduction at 36-wk as the primary efficacy outcome for ORIGIN-3 is at the core of Vera\u2019s FDA submission. The 203-patient FAS that constitutes the IA should be rock-solid by now (see timeline of primary study completion) and we should be told which graph is correct.<\/p>\n\n\n

\n
\"\"<\/a><\/figure>\n<\/div>\n\n\n

<\/p>\n\n\n\n

The Vera team is now compiling the atacicept NDA dossier.  We are anxious to learn the final results.<\/p>\n\n\n\n

ABBREVIATIONS
<\/strong>Gd-IgA1        galactose-deficient IgA1
IA                   interim analysis
FAS               full analysis set
UPCR           urinary protein to creatinine ratio<\/p>\n\n\n\n

REFERENCES
<\/strong>[1]<\/a> Tumlin J.  Efficacy and Safety of Povetacicept in Patients with IgAN and Primary Membranous Nephropathy (pMN) at 48 Weeks of Treatment: The RUBY-3 Study.  SA-OR091.  JASN 36(10S):10.1681\/ASN.20253s04myx7, October 2025
[2]<\/a> Lafayette R.  ORIGIN 3: A Phase 3 Trial of Atacicept in IgAN.  TH-OR083JASN (10S):10.1681\/ASN.202589fw4b2p, October 2025.
[3]<\/a> Lafayette R.  A Phase 3 Trial of Atacicept in Patients with IgA Nephropathy.  NEJM. 2025 Nov 6. doi: 10.1056\/NEJMoa2510198.<\/p>\n","protected":false},"excerpt":{"rendered":"

Two posters on tacicepts caught our eyes. First is the Tumlin publication on povetacicept, an oral presentation in the “Late-Breaking Research” session. 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 Continue reading TACICEPTS VYING FOR YOUR ATTENTION<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":5781,"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":[1271,2209,2529,2531,2532,2194,2533,2408,2530,1583,2211,2212,2536,2210,2229,2208,2230,2534,2226],"class_list":["post-5771","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-data-cleaning","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-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\/TACICEPTS-VYING-FOR-ATTENTION-scaled.jpg?fit=2560%2C720&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-1v5","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":5771,"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":5735,"url":"https:\/\/allphasepharma.com\/dir\/2025\/11\/08\/5735\/comparison-of-baff-april-inhibitors-2\/","url_meta":{"origin":5771,"position":1},"title":"COMPARISON OF BAFF \/ APRIL INHIBITORS \u2013 2","author":"Harald","date":"November 8, 2025","format":false,"excerpt":"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\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\/atacicept-ORIGIN-3-Interim-e1762657582817.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/atacicept-ORIGIN-3-Interim-e1762657582817.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/11\/atacicept-ORIGIN-3-Interim-e1762657582817.jpg?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":4416,"url":"https:\/\/allphasepharma.com\/dir\/2025\/05\/30\/4416\/baff-april-inhibitors-homing-in-on-igan\/","url_meta":{"origin":5771,"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. They were tested in a broad gamut of B-cell indications but failed to show efficacy in many. 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":5771,"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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