Manos Perros, Entasis CEO

As­traZeneca's for­mer an­tibi­otics unit claims a PhI­II win in drug-re­sis­tant bac­te­ria af­fect­ing sick­ly pa­tients

The man­age­ment team at En­ta­sis, As­traZeneca’s old an­tibi­otics unit spun out six years ago, has a new dataset it’s sim­ply de­light­ed to share.

En­ta­sis re­vealed Phase III da­ta out­lin­ing how an an­tibi­ot­ic for in­fec­tions caused by Acine­to­bac­ter bau­man­nii reached its pri­ma­ry end­point of non-in­fe­ri­or­i­ty. Re­searchers com­pared the pro­gram — known as sul­bac­tam-dur­lobac­tam or SUL-DUR — to the an­tibi­ot­ic col­istin, say­ing their drug saw low­er lev­els of all-cause mor­tal­i­ty af­ter four weeks in treat­ment-re­sis­tant pa­tients.

In­vestors gave the news a mut­ed golf clap, send­ing En­ta­sis shares $ET­TX about 3% high­er in ear­ly Tues­day trad­ing.

Acine­to­bac­ter in­fec­tions gen­er­al­ly at­tack crit­i­cal­ly ill pa­tients, En­ta­sis says, en­ter­ing the blood­stream and some­times caus­ing pneu­mo­nia. It’s a class of bac­te­ria that can be­come re­sis­tant to oth­er types of an­tibi­otics such as car­bapen­ems, a com­mon­ly used med­ica­tion for bac­te­r­i­al in­fec­tions world­wide.

There are lim­it­ed treat­ment op­tions should pa­tients find them­selves suf­fer­ing from a drug-re­sis­tant bac­te­ria, the void En­ta­sis hopes to fill. Its sci­en­tists are work­ing not just on Acine­to­bac­ter in­fec­tions but a whole host of oth­er an­tibi­ot­ic meds, and just last month an­nounced they would start hu­man tri­als for a pro­gram that could kill a heav­i­ly scru­ti­nized bug in Pseudomonas.

Tues­day’s da­ta come from a study that en­rolled 207 pa­tients. En­ta­sis set up two parts for the tri­al — Part A ran­dom­ized the in­fect­ed in­di­vid­u­als in­to SUL-DUR and col­istin arms, while Part B was open-la­bel, ex­am­in­ing SUL-DUR in pre­vi­ous­ly failed treat­ments. Of the 125 evalu­able pa­tients in Part A, 19% of pa­tients died on SUL-DUR af­ter 28 days com­pared to 32.3% on col­istin.

Be­cause the pri­ma­ry end­point was non-in­fe­ri­or­i­ty, En­ta­sis did not pow­er the study for p-val­ues here, CEO Manos Per­ros said in a Tues­day morn­ing in­vestor call. In Part B, En­ta­sis said it saw a sim­i­lar all-cause mor­tal­i­ty rate for SUL-DUR at 17.9% of pa­tients.

But where En­ta­sis sees its drug set­ting it­self apart from com­peti­tors is in safe­ty, par­tic­u­lar­ly in the end­point look­ing at nephro­tox­i­c­i­ty. Re­searchers saw a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in nephro­tox­i­c­i­ty be­tween the SUL-DUR and col­istin groups in Part A: nephro­tox­i­c­i­ty was 13.2% in the treat­ment arm ver­sus 37.6% in the con­trol, good for a p-val­ue of p=0.0002.

“This is the key dif­fer­en­tia­tor,” En­ta­sis CMO David Al­tarac said on the call.

Over­all ad­verse events were com­pa­ra­ble be­tween the groups, but drug-re­lat­ed side ef­fects were nu­mer­i­cal­ly low­er among those tak­ing SUL-DUR. On­ly 11 of 91 pa­tients in the ac­tive arm ex­pe­ri­enced a drug-re­lat­ed ad­verse event, com­pared to 26 of 86 tak­ing col­istin.

Big Phar­ma large­ly left the an­tibi­otics space around the time As­traZeneca spun out En­ta­sis in 2015, as dis­mal re­sults con­tin­ued to hound clin­i­cal tri­als. The field al­so con­tin­ues to see a large­ly bro­ken re­im­burse­ment sys­tem, and the WHO has warned the pipeline for new an­tibi­otics is grow­ing ever spars­er.

But if every­thing goes right for En­ta­sis, the com­pa­ny will be ready to sub­mit its NDA in mid-2022.

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