Aldeyra shares spiral after a late-stage failure in dry eye disease — but that won’t stop its pursuit of an NDA

Aldeyra Ther­a­peu­tics’ shares tanked in pre­mar­ket trad­ing af­ter the com­pa­ny ad­mit­ted its dry eye can­di­date re­prox­alap missed the pri­ma­ry end­point in a topline Phase III read­out — but who needs the pri­ma­ry?

De­spite the late-stage fail­ure, Aldeyra is charg­ing ahead with an­oth­er Phase III tri­al, and CEO Todd Brady is con­fi­dent a sec­ondary end­point will lead the can­di­date to suc­cess.

‘We con­tin­ue to ad­vance re­prox­alap to­ward NDA sub­mis­sion as we fo­cus on the com­ple­tion of TRAN­QUIL­I­TY-2 and en­roll­ment in the 12-month safe­ty tri­al,’ he said in a state­ment.

In­vestors weren’t as con­fi­dent. $ALDX shares slipped more than 38% in pre­mar­ket trad­ing Tues­day, pric­ing in at $4.39 — a long fall from yes­ter­day’s clos­ing price of $7.13.

While re­prox­alap met the pri­ma­ry end­point of oc­u­lar red­ness in a Phase II tri­al, the end­point didn’t reach sta­tis­ti­cal sig­nif­i­cance in the Phase III TRAN­QUIL­I­TY read­out, Aldeyra an­nounced on Mon­day with­out pro­vid­ing any hard num­bers.

It did, how­ev­er, meet the sec­ondary end­point for dry eye dis­ease based on the Schirmer test, which de­ter­mines whether a pa­tient’s eye pro­duces enough tears. Again with­out pro­vid­ing the ac­tu­al re­sult, Aldeyra said the p-val­ue there was 0.0001.

The Schirmer test has been ac­cept­ed by the FDA as part of the ba­sis for ap­proval of oth­er dry eye prod­ucts, the Lex­ing­ton, MA-based com­pa­ny said. So it’s go­ing forth with an­oth­er Phase III study, dubbed TRAN­QUIL­I­TY-2 — ex­cept this time, it’s mod­i­fy­ing the tri­al so that the pri­ma­ry end­point will be met if sta­tis­ti­cal sig­nif­i­cance is achieved in ei­ther oc­u­lar red­ness or the Schirmer test.

In ad­di­tion, tar­get en­roll­ment has been upped from 300 to 400 pa­tients, ac­cord­ing to Aldeyra. Top-line re­sults there are ex­pect­ed in mid-2022.

‘Fol­low­ing the achieve­ment of sta­tis­ti­cal sig­nif­i­cance in oc­u­lar red­ness in our re­cent Phase 2 clin­i­cal tri­al, the achieve­ment of sta­tis­ti­cal sig­nif­i­cance of Schirmer test in TRAN­QUIL­I­TY may pro­vide an ad­di­tion­al op­tion to sat­is­fy the re­main­ing ob­jec­tive sign re­quire­ment for dry eye dis­ease NDA sub­mis­sion,’ Brady said in a state­ment.

In­vestors cheered on Aldeyra a few years ago when re­prox­alap achieved sta­tis­ti­cal sig­nif­i­cance in a Phase IIb read­out for two dos­es rat­ed on the Four-Symp­tom Oc­u­lar Dry­ness Score and the Over­all Oc­u­lar Dis­com­fort Symp­tom Score. How­ev­er, some care­ful ob­servers no­ticed that the high dose hit at week 8, then lost sta­tis­ti­cal sig­nif­i­cance at week 12, while the low dose out­per­formed the high dose at week 12 — rais­ing some ques­tions about dura­bil­i­ty and dose re­sponse.

Pend­ing the en­roll­ment of an on­go­ing 12-month safe­ty study and the out­come of TRAN­QUIL­I­TY-2, Brady says an NDA sub­mis­sion could come as soon as mid-2022.

This isn’t the in­dus­try’s on­ly fail­ure this year in dry eye dis­ease.

In Oc­to­ber, Oc­u­lar Ther­a­peu­tix an­nounced its lead ex­per­i­men­tal eye drug, OTX-CSI (cy­closporine in­tra­canalic­u­lar in­sert), failed to hit the pri­ma­ry end­point in a Phase II tri­al: in­creased tear pro­duc­tion at 12 weeks as mea­sured by the Schirmer test com­pared to the ve­hi­cle con­trol group. Aerie’s dry eye dis­ease drug al­so missed the pri­maries in a Phase IIb tri­al back in Sep­tem­ber, but the com­pa­ny said it would plunge right in­to two Phase III tri­als any­way.

CALQUENCE is a registered trademark of the AstraZeneca group of companies.

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Graphic: Alexander Lefterov for Endpoints News

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