Austin’s Ae­glea Bio­Ther­a­peu­tics is hop­ing to blaze a path re­duc­ing a key amino acid bio­mark­er for a rare wast­ing meta­bol­ic dis­ease with its en­gi­neered en­zyme ap­proach. But with a piv­otal out­comes read­out bod­ing poor­ly for the drug’s ben­e­fit, Ae­glea hopes it still has enough da­ta on hand to catch the FDA’s eyes.

Ae­glea’s pegzi­larginase, a re­com­bi­nant en­zyme de­signed to de­grade the amino acid argi­nine, hit its pri­ma­ry end­point re­duc­ing argi­nine lev­els in the blood over place­bo in pa­tients with the rare meta­bol­ic dis­ease arginase 1 de­fi­cien­cy (ARG1-D), the Austin-based biotech said Mon­day.

The 21 pa­tients dosed with pegzi­larginase post­ed an 80% re­duc­tion in mean plas­ma argi­nine over place­bo at six months, good for a sta­tis­ti­cal­ly sig­nif­i­cant p=<0.0001. Mean­while, 90.5% of pa­tients re­ceiv­ing the en­zyme reached nor­mal plas­ma argi­nine lev­els com­pared with no pa­tients in the con­trol arm.

The goal of the Phase III PEACE study was to demon­strate that sig­nif­i­cant­ly re­duc­ing el­e­vat­ed argi­nine lev­els — a ther­a­peu­tic route with no FDA-ap­proved treat­ments — would show a cor­re­la­tion with im­proved out­comes for pa­tients with ARG1-D, which typ­i­cal­ly presents in ear­ly child­hood with pa­tients ex­pe­ri­enc­ing spas­tic­i­ty, seizures, de­vel­op­men­tal de­lay, in­tel­lec­tu­al dis­abil­i­ty and ear­ly mor­tal­i­ty.

But those weren’t the re­sults Ae­glea turned up.

On two key sec­ondary end­points, in­clud­ing im­prove­ments in a two-minute walk test and a catch-all mo­bil­i­ty test known as GMFM-E, peglizarginase failed to best place­bo de­spite show­ing what Ae­glea called “pos­i­tive trends” on pa­tient out­comes.

For the two-minute walk test, pa­tients dosed with peglizarginase post­ed a mean in­crease in dis­tance walked from base­line of 7.4 me­ters com­pared with an in­crease of 1.9 me­ters in con­trol pa­tients. That came out to an ug­ly p=0.5961, far be­low the bar for sta­tis­ti­cal sig­nif­i­cance. On the GMFM-E test, pa­tients dosed with pegzi­larginase showed a 4.2-unit in­crease over base­line com­pared with a 0.4-unit de­cline for place­bo pa­tients (p=0.1087).

“We are dis­ap­point­ed this isn’t a sta­tis­ti­cal­ly sig­nif­i­cant re­sult,” Ae­glea Chief De­vel­op­ment Of­fi­cer Er­ic Brad­ford said on a call with an­a­lysts Mon­day. “It high­lights the chal­lenge of de­sign­ing a study where there’s no clin­i­cal prece­dent.”

Ae­glea said it didn’t flag any new safe­ty con­cerns in the study and no pa­tients drop­ping out due to dos­ing.

Even with no out­comes im­prove­ments to show, Ae­glea thinks it has enough da­ta in hand to go to the FDA for a rul­ing. The biotech said it plans to file a BLA in the first of the year and is plan­ning con­cur­rent mar­ket­ing fil­ings in the “cer­tain coun­tries in Eu­rope and the Mid­dle East” along­side part­ner Im­med­ica Phar­ma AB.

Some of that op­ti­mism is tied to re­sults from the open-la­bel ex­ten­sion por­tion of a sin­gle-arm Phase I/II study, in which 11 of 14 pa­tients showed im­prove­ments across a slate of three mo­bil­i­ty tests at 56 weeks. Those re­sults, of course, weren’t pow­ered for sig­nif­i­cance and weren’t con­trolled, cast­ing doubt on whether reg­u­la­tors will be con­vinced.

How­ev­er, it wouldn’t be the first time the agency has giv­en tac­it ap­proval to a sur­ro­gate end­point with­out the out­comes da­ta to back it up. From Bio­gen’s Aduhelm to Sarep­ta’s Ex­ondys 51, the agency has at times hand­ed out ac­cel­er­at­ed ap­provals based on a high de­gree of con­fi­dence a giv­en bio­mark­er will even­tu­al­ly lead to sig­nif­i­cant clin­i­cal ben­e­fit but with­out the ac­tu­al ben­e­fits shown in pa­tients.

In this case, Ae­glea’s out­comes re­sults are more ex­plic­it, like­ly lead­ing the biotech to pitch a “to­tal­i­ty of da­ta” ar­gu­ment to reg­u­la­tors based on in­cre­men­tal im­prove­ments and a dearth of ther­a­peu­tic op­tions — an ar­gu­ment CEO An­tho­ny Quinn high­light­ed dur­ing the team’s call with an­a­lysts.

Mean­while, Ae­glea has rolled the PEACE tri­al pa­tients in­to a long-term ex­ten­sion por­tion, where Ae­glea hopes to show sus­tained argi­nine re­duc­tion as well as im­prove­ments in clin­i­cal out­comes.

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.