Lonvoguran Ziclumeran — In Vivo CRISPR Gene Editing in Hereditary Angioedema
New England Journal of Medicine, 2026 · paper · Clinical trials
A phase 3 randomized trial of a single infusion of the CRISPR gene-editing treatment lonvo-z versus placebo in 80 patients with hereditary angioedema. Monthly attack rates were 0.26 versus 2.10, an 87% relative reduction.
3 findings
Substance The text says "A total of 64 patients (43 in the lonvo-z group and 21 in the placebo group) reached at least the week 28 evaluation". Figure 1 lists 44 lonvo-z and 21 placebo patients at risk at week 28, and the Table 2 footnote ¶ says "At week 28, data were available for 44 patients in the lonvo-z group and 20 patients in the placebo group".
- p. 4 Results, Patients
64 patients (43 in the lonvo-z group and 21 in the placebo group) reached at least the week 28 evaluation
- p. 7 Figure 1, No. at Risk, Lonvo-z row, week 28
44
- p. 6 Table 2 footnote ¶
data were available for 44 patients in the lonvo-z group
- p. 4 Results, Patients
A total of 64 patients (43 in the lonvo-z group and 21 in the placebo group) reached at least the week 28 evaluation
Only the authors can say what is right here.
Judge's note: I checked the page images. Page 4 text: 43/21 (total 64; footnote ‡ of Table 2 says 16 had not reached week 28, which fits 80−64). Figure 1 No. at Risk, week 28: Lonvo-z 44, Placebo 21 (total 65). Table 2 footnote ¶: AE-QoL data at week 28 for 44 lonvo-z and 20 placebo patients (total 64). Week-28 AE-QoL data for 44 lonvo-z patients cannot sit beside only 43 lonvo-z patients reaching week 28 unless a visit window or a different definition applies, and the paper defines neither for the at-risk counts or the AE-QoL availability. I found no explanation in the Figure 1 legend or the footnotes. Only the authors can say which split is correct.
Second check: another model agreed
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Substance In Table 3 (lonvo-z, N=52) the Fatigue row prints "7 (14)"; 7/52 is 13.5%, which rounds to 13%, and Table 1 prints the same 7 of 52 as "7 (13)".
- p. 8 Table 3, Fatigue row, lonvo-z column
7 (14)
- p. 5 Table 1, Mild severity row, lonvo-z column (same n/N printed as 13%)
7 (13)
- p. 8 Table 3, Fatigue and Nasopharyngitis rows, lonvo-z column
Fatigue 7 (14)
Judge's note: The header of Table 3 on p. 8 gives Lonvo-z N=52. The other rows round correctly (6/52 printed 12, 5/52 printed 10, 10/52 printed 19, 32/52 printed 62). Table 1 Mild row prints 7 (13) with the same denominator. 13.46 is not a rounding tie. No footnote gives a different denominator.
Second check: another model agreed
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Substance In Table 3 (lonvo-z, N=52) the Nasopharyngitis row prints "7 (14)"; 7/52 is 13.5%, which rounds to 13%.
- p. 8 Table 3, Nasopharyngitis row, lonvo-z column
7 (14)
Judge's note: This is the same rounding defect as C005 but in a separate table cell (Nasopharyngitis row, lonvo-z column), so I kept it as its own cluster. The placebo cell in the same row, 9/28 = 32%, is correct. The denominator is 52 per the header, and no footnote alters it.
Second check: another model agreed
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5 minor (typos and the like; most checked by the judge only)
Wording The Discussion says aminotransferase elevations "occurred in approximately 10 to 15% of patients treated with lonvo-z", while the Results give a single lonvo-z figure, "eight patients (15%)".
- p. 10 Discussion, paragraph on other in vivo gene-editing trials
which occurred in approximately 10 to 15% of patients treated with lonvo-z
- p. 8 Results, Safety (liver enzymes)
elevated levels of aspartate aminotransferase, alanine aminotransferase, or both were observed in eight patients (15%)
Only the authors can say what is right here.
Judge's note: Page 10: the sentence sits in a paragraph beginning "In this trial". Page 8 Results: lonvo-z 8 patients (15%), placebo 3 patients (11%). No lonvo-z value near 10% is reported in this trial. The range may be pooling phase 1–2 data, but the text does not say so. This is a wording ambiguity for the authors to resolve.
Second check: another model agreed
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Typo The instrument is called "Angioedema-Quality of Life (AE-QoL) questionnaire" in the Table 1 footnote § but "Angioedema Quality of Life (AE-QoL) questionnaire" in the Methods (p. 3) and in ref 12.
- p. 3 Trial End Points
Angioedema Quality of Life (AE-QoL) questionnaire
- p. 5 Table 1 footnote §
The Angioedema-Quality of Life (AE-QoL) questionnaire
Judge's note: I looked at both crops. The hyphen is printed in the Table 1 footnote and missing in the Methods text. This is a house-style inconsistency only and does not change the meaning.
Second check: none (judge only)
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Typo There is a duplicated negation on p. 4: "The 95% confidence intervals have not been not adjusted for multiplicity" should read "have not been adjusted".
- p. 4 Statistical Analysis, end of paragraph on missing data
The 95% confidence intervals have not been not adjusted for multiplicity
- p. 4 Statistical Analysis, last paragraph start
have not been not adjusted for multiplicity
Judge's note: The page image shows the double "not" as printed, so this is not an extraction artefact. The intended meaning is clear from the rest of the sentence ("should not be used in place of hypothesis testing").
Second check: none (judge only)
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Typo In Table 2 the row label "LS mean change from baseline to wk 28 in AE-QoL questionnaire total score — (95% CI)" has an em dash with no unit after it.
- p. 6 Table 2, AE-QoL row label
questionnaire total score — (95% CI)
Judge's note: I looked at the Table 2 crop. The other LS mean rows end in "(95% CI)" with no dash, and "— no. (%)" rows give a unit after the dash. Here the dash is followed by nothing, so either a unit (e.g., points) is missing or the dash is stray. This is cosmetic.
Second check: none (judge only)
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Typo The title of reference 11 misspells the disease: "in patients with hereditary angiodema" (should be "angioedema").
- p. 11 Reference 11
in patients with hereditary angiodema
- p. 11 Reference 11 title
hereditary angiodema
Judge's note: The reference list image on p. 11 shows "angiodema" printed in ref 11. Everywhere else the paper uses "angioedema".
Second check: none (judge only)