Snakebit Angion reports another miss for lead program, as biotech prepares to shift its ‘primary focus’

An­gion’s lead or­gan dam­age drug took two strikes ear­li­er this year, flop­ping as a re­pur­posed ef­fort for Covid-19 and whiff­ing in high-risk kid­ney trans­plant pa­tients. The biotech re­port­ed a third on Thurs­day, rais­ing se­ri­ous ques­tions about the pro­gram’s fu­ture.

In a Phase II study look­ing at some car­diac surgery pa­tients at risk of kid­ney in­jury, An­gion re­port­ed its ANG-3777 can­di­date missed bad­ly on the pri­ma­ry end­point. The re­sults come about a month and a half af­ter the kid­ney trans­plant study and less than five months af­ter the Covid-19 tri­al, os­ten­si­bly leav­ing the can­di­date on the chop­ping block.

$ANGN shares were down about 18% af­ter the bell Thurs­day evening and in­to ear­ly Fri­day morn­ing. Dur­ing a Thurs­day af­ter­noon in­vestor call, CEO Jay Venkate­san im­plied this could be end of the road for ANG-3777, say­ing An­gion’s ‘pri­ma­ry fo­cus’ mov­ing for­ward will be its Phase II ty­ro­sine ki­nase re­cep­tor in­hibitor, ANG-3070. But An­gion and its part­ner Vi­for Phar­ma will need to fur­ther re­view the da­ta, he said, not­ing a de­ci­sion will like­ly be made some­time in ear­ly 2022 about next steps.

Much of An­gion’s fo­cus post-re­veal dealt with a sec­ondary end­point that al­so missed sta­tis­ti­cal sig­nif­i­cance, but one which the com­pa­ny said is more com­mon­ly used as a reg­u­la­to­ry bench­mark. In dam­age con­trol mode on the in­vestor call, Venkate­san stressed this point and not­ed An­gion still wants to take a clos­er look at the da­ta.

‘We have been clear with in­vestors that this tri­al was not in­tend­ed to gen­er­ate sta­tis­ti­cal­ly sig­nif­i­cant re­sults, par­tic­u­lar­ly on the [sec­ondary] MAKE90 end­point, where we be­lieve we were not suf­fi­cient­ly pow­ered,’ Venkate­san said.

The chief added there was a ‘po­ten­tial mean­ing­ful’ ben­e­fit here and would like­ly be the pri­ma­ry end­point in a piv­otal Phase III study, should An­gion elect to move for­ward.

For Thurs­day’s pri­ma­ry, re­searchers mea­sured the per­cent­age in­crease in serum cre­a­ti­nine based up­on area un­der the curve, start­ing at 24 hours af­ter pa­tients’ surgery through day 6. ANG-3777 in­duced an 8.4% in­crease while place­bo pa­tients saw a 7.3% in­crease, amount­ing to a mis­er­able p-val­ue of p=0.77.

An­gion then looked at MAKE90 events be­tween the two groups, an end­point ob­serv­ing how many pa­tients suf­fer death, ini­ti­a­tion of re­nal re­place­ment ther­a­py or a greater than 25% de­cline in eGFR with­in 90 days of their surgery. Few­er pa­tients in the drug arm saw such events at 14.7%, com­pared to 21.5% on place­bo, good for a p-val­ue of p=0.155.

De­spite this be­ing a sta­tis­ti­cal­ly in­signif­i­cant re­sult, Venkate­san de­scribed this as an ‘en­cour­ag­ing’ re­sult.

The on­ly end­point that reached sta­tis­ti­cal sig­nif­i­cance in this tri­al was an­oth­er sec­ondary mea­sure in which few­er ANG-3777 pa­tients saw a greater than 25% de­crease in eGFR af­ter three months ver­sus place­bo.

ANG-3777’s fate comes af­ter the two ear­li­er miss­es this year. The can­di­date missed the pri­ma­ry and sec­ondary end­points in a Phase II study in se­vere Covid-19 pa­tients at risk for ARDS and failed to beat out place­bo in im­prov­ing eGFR in pa­tients who had re­ceived a de­ceased donor kid­ney trans­plant at risk of de­vel­op­ing de­layed graft func­tion.
https://endpts.com/snakebit-angion-reports-another-miss-for-lead-program-as-biotech-prepares-to-shift-its-primary-focus/