Todd Brady, Aldeyra CEO

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.

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End­points 20(+2) un­der 40, 2023; Bio­phar­ma's high­est-paid CEOs; N-of-1 CRISPR sto­ry goes on af­ter tragedy; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We will be off Monday in observance of Memorial Day — and when we get back, it will be a straight march to ASCO, BIO and more. Enjoy the (long) weekend!

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Teresa Bitetti, Takeda's president of the global oncology business unit

Take­da wins pri­or­i­ty re­view for $400M col­orec­tal can­cer drug, li­censed from Hutchmed in Jan­u­ary

Takeda and Hutchmed scored a priority review Thursday afternoon for a colorectal cancer drug, the companies announced.

The experimental drug in question is fruquintinib, previously approved in China in 2018 to treat metastatic colorectal cancer. Takeda and Hutchmed are aiming to bring fruquintinib to the US and other countries outside China in the same indication, and the FDA set its decision date for Nov. 30 of this year.

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Douglas Love, Annexon CEO

An­nex­on’s GA drug miss­es on pri­ma­ry goal but win on vi­su­al acu­ity will be fo­cus of planned late-stage tri­al

Annexon’s complement inhibitor didn’t prove better than sham at reducing lesion growth in a leading cause of blindness, but the biotech still plans to move forward on the back of secondary endpoints showing visual acuity preservation, which will “certainly” be the primary goal in a late-stage trial to be discussed shortly with the FDA, CEO Douglas Love told Endpoints News. 

The California biotech’s ANX007 was not statistically significant compared to pooled sham, the comparator, at 12 months in patients with geographic atrophy, per a Wednesday presentation. In every-month dosing, the GA lesion area changed about 6.2% from baseline (p=0.526) and 1.3% (p=0.896) in the every-other-month group. In a March note, Jefferies analyst Suji Jeong said a reduction of 20% to 30% would be “encouraging.”

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FDA ap­proves Lex­i­con’s heart-fail­ure drug af­ter de­feat in di­a­betes

The FDA on Friday approved Lexicon’s heart failure drug sotagliflozin following a string of setbacks for the pharma company, including an FDA rejection in diabetes and the loss of a development deal with Sanofi.

The dual SGLT1 and SGLT2 inhibitor will be marketed as Inpefa and is a once-daily tablet. It’s been approved to reduce the risk of cardiovascular death and heart failure-related hospitalization or urgent visits in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors. The label spans the range of left ventricular ejection fraction, including preserved ejection fraction and reduced ejection fraction, as well as patients with or without diabetes, Lexicon said Friday.

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Rich Horgan (R) with his late brother, Terry

Rich Hor­gan spear­head­ed a gene ther­a­py for his broth­er. The tri­al end­ed in tragedy, but the work con­tin­ues for more pa­tients

Rich Horgan’s quest to create a custom gene therapy for his brother, Terry, ended in tragedy. But Horgan doesn’t believe it’s the end of the story.

Terry, a 27-year-old patient with Duchenne muscular dystrophy, died last October just eight days after receiving the therapy in a clinical trial in which he was the only participant. The case raised questions about the safety of certain gene therapies and what would happen to other drug programs under a nonprofit that Horgan created, called Cure Rare Disease.

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Bio­phar­ma's 20 high­est-paid CEOs of 2022, each bring­ing in $20M+ pay­days

Even in a down year for much of the biopharma market, 20 CEOs brought in pay packages valued at more than $20 million, an Endpoints News analysis found.

Endpoints collected data on more than 350 CEO compensation packages, covering a wide range of pharma, biotech, and life sciences companies. All told, the 20 largest earners made over $725 million in 2022 — an average package of $36.4 million. Three brought in paydays over $50 million, and one CEO broke the $100 million mark.

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The 20(+2) un­der 40: Your guide to the next gen­er­a­tion of biotech lead­ers

This year’s list of 20 biotech leaders under the age of 40 includes a huge range of ambitions. Some of our honorees are planning to create the next big drug giant. Others are pushing the bounds of AI. One is working to revolutionize TB testing. All are compelling talents who are still young in age, but already far along in achievement.

And, as in years past, we went over. The 20 are actually 22 because of two double profiles that reflect how important teamwork is in the industry. As one of our honorees, Joe Illingworth of DJS Antibodies, told me in our interview, “It takes a village to raise a biotech.”

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Eu­ro­pean Com­mis­sion to re­ceive few­er Pfiz­er-BioN­Tech vac­cine dos­es un­der amend­ed con­tract

The European Commission has made a few changes to its vaccine contract with Pfizer and BioNTech, reducing the dose volume while extending the delivery timeline to cope with “evolving public health needs.”

The Commission previously struck a contract in May 2021 for 900 million doses, with the option to purchase another 900 million. Of those, 450 million were expected to be delivered in 2023, though an amendment now calls for fewer doses. While neither the Commission nor Pfizer and BioNTech have revealed an exact amount, an unnamed source told Reuters that the amendment reduces the remaining expected doses by about a third.

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