Aldeyra’s at­tempt at treat­ing dry eye dis­ease has seen a few ups and downs in re­cent years, but the biotech’s sight to ap­proval got a lit­tle clear­er Tues­day with a crossover tri­al suc­cess that will pad its case to the FDA this quar­ter.

In De­cem­ber 2021, the com­pa­ny’s drug, re­prox­alap, failed to reach sta­tis­ti­cal sig­nif­i­cance in re­duc­ing eye red­ness in a Phase III tri­al, but Aldeyra scrapped that pri­ma­ry end­point in a sep­a­rate late-stage study. The tri­al end­ed up achiev­ing the new pri­ma­ry end­point, a test mea­sur­ing tear pro­duc­tion, last month.

Now, a crossover study shows the drug was bet­ter than the con­trol at both of those end­points, as well as in mul­ti­ple sec­ondary goals: dry­ness, dis­com­fort, grit­ti­ness, sting­ing, burn­ing and itch­ing. With all the da­ta in hand, the Lex­ing­ton, MA-based biotech will take its drug to the FDA this quar­ter, CEO and pres­i­dent Todd Brady said on an in­vestor call Tues­day morn­ing.

The small biotech, which had $216.9 mil­lion on hand at the end of March, is go­ing up against Big Phar­ma in dry eye dis­ease, in­clud­ing No­var­tis’ Xi­idra and Ab­b­Vie/Al­ler­gan’s Resta­sis.

“Ap­prov­abil­i­ty has been put to bed. The no­tion that re­prox­alap is ac­tive and is safe across a va­ri­ety of dif­fer­ent tri­al de­signs, acute and chron­ic, cham­ber, field-based stud­ies, etc., I think it’s sol­id,” Brady said on the in­vestor call.

In at­tempt­ing to dif­fer­en­ti­ate it­self from drugs on the mar­ket, Aldeyra point­ed to its mar­ket re­search, claim­ing about 60% to 70% of pa­tients dis­con­tin­ue Xi­idra and Resta­sis, with me­di­an time of stop­ping use at one month and three months, re­spec­tive­ly.

The first dry eye Resta­sis gener­ic, af­ter near­ly 20 years on the mar­ket, was ap­proved by the FDA in Feb­ru­ary. The drug hauled in $1.29 bil­lion for Ab­b­Vie last year.

Aldeyra’s 63-pa­tient crossover study test­ed the 0.25% oph­thalmic so­lu­tion and found the in­ves­ti­ga­tion­al treat­ment was bet­ter at re­duc­ing eye red­ness “as soon as 10 min­utes af­ter” en­ter­ing the dry eye cham­ber, the first time at which it was as­sessed by hu­mans and not dig­i­tal pho­tog­ra­phy, the com­pa­ny said. The oth­er pri­ma­ry end­point, the Schirmer test, was al­so achieved af­ter one day of dos­ing, Aldeyra said. Pa­tients re­ceived four dos­es on day one and two dos­es the fol­low­ing day.

“To our knowl­edge, an ad­e­quate and well-con­trolled crossover tri­al in dry dis­ease has not been pre­vi­ous­ly per­formed, per­haps be­cause most in­ves­ti­ga­tion­al dry dis­ease drugs re­quire at least two weeks to demon­strate even mod­est ac­tiv­i­ty,” Brady said on the call.

Brady de­scribed the crossover tri­al as the meat of the NDA pack­age that will go to the FDA’s doorsteps lat­er this quar­ter.

“I think we can all agree at this point that the crossover re­sults will be large­ly front and cen­ter for a cou­ple of rea­sons. Num­ber one, the re­sults are out­stand­ing, and I think de­fin­i­tive. Num­ber two, the crossover has in a sense demon­strat­ed, at least in this case, that it can re­duce the ma­jor prob­lem in dry eye dis­ease tri­als, which is vari­abil­i­ty from pa­tient to pa­tient,” Brady said.

The biotech said there were no treat­ment-emer­gent mod­er­ate or se­ri­ous ad­verse events in the study of the RASP in­hibitor, which aims to re­duce oc­u­lar in­flam­ma­tion. Three pa­tients stopped tak­ing the treat­ment be­cause of ad­verse events, in­clud­ing one dur­ing the ad­min­is­tra­tion of the in­ves­ti­ga­tion­al eye drop. In­clud­ing pa­tients in the crossover study, the eye drop has now been test­ed in more than 1,800 pa­tients.

Asked by an an­a­lyst if the com­pa­ny would move for­ward with a study of the drug look­ing specif­i­cal­ly at the Schirmer test, Brady said that tri­al is “ef­fec­tive­ly on hold giv­en the re­sults that we an­nounced to­day.”

“In the very un­like­ly sit­u­a­tion that there are re­main­ing ques­tions about the clin­i­cal pack­age [dur­ing the pre-NDA meet­ing], we’ll be pre­pared to ini­ti­ate that tri­al, ef­fec­tive­ly, im­me­di­ate­ly,” Brady said.

Aldeyra is al­so test­ing re­prox­alap’s po­ten­tial in al­ler­gic con­junc­tivi­tis. The biotech cleared a Phase III in the sea­son­al al­ler­gy last year, show­ing that pa­tients scratched their eyes few­er times af­ter be­ing ex­posed to rag­weed pollen when giv­en the drug.

Amgen had hoped that its latest study matching its landmark KRAS G12C drug Lumakras with checkpoint inhibitors would open up its treatment horizons and expand its commercial potential. Instead, the combo spurred safety issues that blunted efficacy and forced the pharma giant to alter course on its treatment strategy, once again disappointing analysts who have been tracking the drug’s faltering sales and limited therapeutic reach.

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The field of gene therapy has been diligently moving forward over the past several decades to bring potentially life-saving treatments to patients with genetic diseases. In addition to two approved adeno-associated viral (AAV) gene therapies, there are more than 250 AAV gene therapies in various clinical trial stages.1 AAV vectors remain the most frequently used vector for delivering therapeutic transgenes to target tissues due to their demonstrated and lasting clinical efficacy and extensive safety track record. As AAV therapies advance through clinical trials and into commercialization, many biotech companies are turning to contract development and manufacturing organizations (CDMOs) to prepare their programs for late-stage clinical and commercial scale manufacturing. Given the scope and scale of the manufacturing needs that will accompany regulatory approvals for these assets, CDMOs continue to expand their capacity to meet the needs of increasing prevalent patient populations. However, despite rapid growth, projected gene therapy manufacturing demands still outpace the collective capacity of the CDMO industry.

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.

One of the cool things about adding EndpointsPharma to the daily roster is that my colleagues can now dedicate time to tracking quarterly updates and tuning into calls with Big Pharma companies. Check out their dispatch from the Q2 earnings below.

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Amgen CEO Bob Bradway is bellying up to the M&A table today, scooping up the newly anointed commercial biotech ChemoCentryx $CCXI and its recently approved rare disease drug for $3.7 billion out of the cash stockpile. The deal comes in at $52 a share — a hefty increase over the $24.11 close yesterday.

Bradway and the Amgen team get a drug called Tavneos (avacopan) in the deal, a complement factor C5a inhibitor OK’d to treat anti-neutrophil cytoplasmic autoantibody (ANCA)-vasculitis, an autoimmune disease which can be lethal.

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Pfizer CEO Albert Bourla has vowed to leave no stone unturned in the search for new biotech deals, and the BD team is not letting him down.

The Wall Street Journal reported today that Pfizer is in the final stages of acquiring Global Blood Therapeutics for $5 billion. According to the Journal report, though, Pfizer is not the only buyer at the deal table and while the pharma giant may be close to clinching it, there are no guarantees it will continue.

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Two of the most outspoken — and successful — drug developers in biotech say they’ve collected early-stage clinical data that are pointing them down the trail to the holy grail in cancer immunotherapy R&D.

While analysts largely busied themselves today with chronicling the ongoing success of Regeneron’s two big cash cows — Dupixent and Eylea — chief scientist George Yancopoulos and CEO Len Schleifer used the Q2 call to spotlight their early success with a combination of the “homegrown” PSMAxCD28 costimulatory bispecific antibody REGN5678 in combination with their PD-1 checkpoint Libtayo. The presentation comes just weeks after Regeneron completed a deal to gather all rights to the PD-1 that had been in Sanofi’s hands. And the two top execs are unstinting in their praise of the potential of a whole set of costimulatory pipeline projects which they say may finally deliver the long-awaited next-level approach to broadening the immunotherapy field of drugs.

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Rising monkeypox cases have put the US on high alert as it announces a national health emergency, which grants the government more power in its response.

The news comes as Bavarian Nordic continues to fill orders for its Jynneos vaccine and other companies – including Moderna – consider jumping into the vaccine race. Meanwhile, the New York Times reports that the US has allowed around 20 million doses of smallpox vaccine in its stockpile to expire.

Al Sandrock is narrowing the focus of Voyager Therapeutics, concentrating on CNS diseases that were the hallmark of his time leading R&D at Biogen, including an emphasis on a familial form of ALS for which his former employer is getting a speedy review at the FDA.

Less than six months into his journey as CEO at Voyager, Sandrock is focusing the preclinical pipeline on Alzheimer’s disease, GBA1 Parkinson’s disease and SOD1 amyotrophic lateral sclerosis, the rare form of ALS for which the FDA will decide whether to approve Biogen’s tofersen by Jan. 25, 2023.

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While Pfizer’s $11.4 billion acquisition of Array BioPharma in the summer of 2019 was mainly focused on oncology, namely Braftovi and Mektovi, there were a few non-cancer assets, including a Phase III drug being tested in a rare cardiovascular disease.

The late-stage trial is now being axed, alongside any further development of the oral small molecule, the pharma giant disclosed after the closing bell on Wednesday. Based on an interim futility analysis of the global Phase III REALM-DCM trial, Pfizer determined a path forward was not in its best interest. Pfizer no longer expected the study would meet its primary goal.

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Bioscience & Technology Business Center The University of Kansas Lawrence, Kansas

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