Aim­ing to up­root the mar­ket for asth­ma at­tacks, As­traZeneca and Avil­lion tout two PhI­II wins for in­haled com­bo drug

A col­lab­o­ra­tion launched in 2018 be­tween As­traZeneca and British com­pa­ny Avil­lion is bear­ing new fruit Thurs­day for a se­vere asth­ma pro­gram.

The As­traZeneca and Avil­lion can­di­date, dubbed PT027, met all pri­ma­ry end­points in two Phase III stud­ies, the com­pa­nies an­nounced Thurs­day. A com­bi­na­tion of the short-act­ing be­ta2-ag­o­nist (SA­BA) al­buterol — a com­mon asth­ma med­ica­tion — and the in­haled cor­ti­cos­teroid budes­onide, PT027 is po­si­tioned to be­come the new stan­dard of care for asth­ma res­cue ther­a­py, As­traZeneca se­nior VP for res­pi­ra­to­ry and im­munol­o­gy Mi­na Makar told End­points News.

Mi­na Makar

“For 40 or 50 years plus, al­buterol has been the stan­dard of care to treat acute symp­toms of asth­ma,” Makar said. “But for all of these years, part of the chal­lenge has been that al­buterol has not been treat­ing the un­der­ly­ing in­flam­ma­tion of the asth­ma, where pa­tients be­gin to over-re­ly on their al­buterol in­halers and not get any re­lief of symp­toms.”

Fur­ther da­ta from more PT027 stud­ies are ex­pect­ed in the first half of next year, but Makar said As­traZeneca and Avil­lion have every­thing they need right now to go to reg­u­la­tors. The com­pa­nies ex­pect to file for ap­proval some­time in 2022.

Re­gard­less of an in­di­vid­ual’s asth­ma sever­i­ty, the vast ma­jor­i­ty of pa­tients car­ry around al­buterol in­halers in case they ex­pe­ri­ence an asth­ma at­tack. The med­i­cine works by loos­en­ing the con­stric­tion of smooth mus­cle in the lungs, but does noth­ing to ad­dress the un­der­ly­ing in­flam­ma­tion of the con­di­tion, Makar said.

Where PT027 hopes to step in is by adding the in­haled cor­ti­cos­teroid to al­buterol as part of the res­cue ther­a­py. It’s a treat­ment that has proven safe among oth­er asth­ma main­te­nance sup­ple­ments like Sym­bi­cort and Trel­e­gy, he added. But the idea be­hind PT027 is that by com­bin­ing the two in the res­cue as­pect, pa­tients will be more like­ly to avoid hos­pi­tal­iza­tion from se­vere at­tacks and the need for oral steroids.

“Those have sig­nif­i­cant tox­i­c­i­ty and bur­den for pa­tients in re­duc­ing ex­ac­er­ba­tions,” Frank Tru­do, As­traZeneca VP of med­ical af­fairs for res­pi­ra­to­ry and im­munol­o­gy, told End­points.

Frank Tru­do

Thurs­day’s an­nounce­ment comes from two late-stage tri­als, en­rolling rough­ly 4,100 pa­tients across the asth­ma spec­trum. The first study saw about 3,100 in­di­vid­u­als with mod­er­ate to se­vere asth­ma tak­ing main­te­nance ther­a­py, while the sec­ond re­cruit­ed about 1,000 pa­tients with mild to mod­er­ate asth­ma who had pre­vi­ous­ly re­ceived a SA­BA or main­te­nance as need­ed.

In the larg­er tri­al, PT027 sta­tis­ti­cal­ly sig­nif­i­cant­ly re­duced the risk of se­vere ex­ac­er­ba­tions com­pared to al­buterol alone, when used as a res­cue ther­a­py in re­sponse to an asth­ma at­tack. As­traZeneca and Avil­lion did not re­lease ex­act fig­ures or a p-val­ue, how­ev­er, not­ing on­ly that the pri­ma­ry was met at both the 180/160 μg and 180/80 μg dos­es.

The sec­ond study mea­sured for a pri­ma­ry end­point against both a com­para­tor and place­bo, with re­searchers look­ing at lung func­tion. Again at both dose lev­els, PT027 showed a sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in lung func­tion mea­sured by the FEV1 test, or how much air an in­di­vid­ual can breathe out in one sec­ond when forcibly ex­hal­ing.

This study al­so re­port­ed no ex­act fig­ures or p-val­ues. As­traZeneca and Avil­lion looked at the PT027 dos­es in com­par­i­son to al­buterol alone, budes­onide alone and place­bo.

As­traZeneca orig­i­nal­ly got the ball rolling with Avil­lion back in March 2018, when the com­pa­nies agreed to co-de­vel­op PT027 for asth­ma. Avil­lion took on all clin­i­cal de­vel­op­ment with As­traZeneca get­ting an op­tion to com­mer­cial­ize and mar­ket the drug in the US up­on a suc­cess­ful ap­proval.

Now with the piv­otal Phase III da­ta in hand, Makar said the pair will need to ini­ti­ate a “com­pre­hen­sive” ed­u­ca­tion pro­gram for pa­tients and physi­cians, giv­en how long al­buterol has been used. But As­traZeneca is pre­pared to do that as it pre­pares the can­di­date for launch.

“Pa­tients and physi­cians are very used to [al­buterol] be­ing the so­lu­tion for acute symp­toms,” Makar said. The pro­grams will em­pha­size how there “needs to be in­haled steroid to deal with the un­der­ly­ing in­flam­ma­tion” in ad­di­tion to al­buterol.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; 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.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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