Ab­b­Vie went all in on cys­tic fi­bro­sis a few years ago, shelling out $245 mil­lion for a port­fo­lio of drugs from Gala­pa­gos in the hopes of de­thron­ing Ver­tex’s block­buster Trikaf­ta. On Fri­day, it be­came clear that Ver­tex still reigns supreme — at least for now.

Ab­b­Vie’s send­ing its ex­per­i­men­tal triplet ther­a­py to the scrap heap af­ter it whiffed on an in­ter­im analy­sis in a Phase II proof-of-con­cept study, ex­ecs re­vealed dur­ing the Q1 call.

Tom Hud­son

“The ef­fi­ca­cy re­sults from this in­ter­im analy­sis did not meet our pre-spec­i­fied cri­te­ria for ad­vanc­ing this triple ther­a­py and de­vel­op­ment,” Tom Hud­son, CSO and se­nior VP of R&D, said.

The study test­ed a dual com­bi­na­tion ther­a­py — in­clud­ing Ab­b­Vie’s C1 cor­rec­tor AB­BV-2222 and po­ten­tia­tor AB­BV-3067 — along­side C2 cor­rec­tor AB­BV-119. Re­searchers con­clud­ed that the ad­di­tion of AB­BV-119 “did not pro­vide a mean­ing­ful im­prove­ment in FEV1,” or forced ex­pi­ra­to­ry vol­ume in 1 sec­ond, an es­tab­lished mark­er of CF. The ad­di­tion of the C2 cor­rec­tor al­so didn’t lead to a mean­ing­ful re­duc­tion in sweat chlo­ride con­cen­tra­tion over the dual ther­a­py.

“We were able to again as­sess the ef­fi­ca­cy of our dual ther­a­py, which per­formed well,” Hud­son said. “So based on the per­for­mance of our dual ther­a­py, we plan to con­tin­ue our CF pro­gram.”

The com­pa­ny is lin­ing up a new C2 cor­rec­tor, AB­BV-567, which it plans to test as a triplet ther­a­py with the ex­ist­ing C1 cor­rec­tor and po­ten­tia­tor in a Phase II study launch­ing be­fore ear­ly next year.

“‘576 is struc­tural­ly dis­tinct from our pre­vi­ous C2 cor­rec­tor ‘119 and has a bet­ter PK pro­file, and pro­vides high­er drug ex­po­sure which has the po­ten­tial to de­liv­er bet­ter ef­fi­ca­cy,” Hud­son said.

Ab­b­Vie’s stock $AB­BV was down more than 8.5% on Fri­day, trad­ing at around $149.92 per share.

R&D chief Michael Sev­eri­no, who’s set to leave the com­pa­ny at the end of next month, made clear ear­li­er this year that Ab­b­Vie in­tends to “ex­ceed the bar that is be­ing set by Ver­tex,” ei­ther by su­pe­ri­or ef­fi­ca­cy marks or a bet­ter tol­er­a­bil­i­ty pro­file.

“We want to have a reg­i­men that is very com­pet­i­tive that de­liv­ers ef­fi­ca­cy to pa­tients in the man­ner that they need to im­prove their long-term func­tion­ing and ul­ti­mate­ly, long-term sur­vival,” he said back in Jan­u­ary.

Resh­ma Ke­wal­ra­mani

Now, Ab­b­Vie’s Phase II flop has cleared the way for Ver­tex to main­tain its tight grip on the CF mar­ket. Trikaf­ta — Ver­tex’s triplet ther­a­py dar­ling first ap­proved back in 2019 — raked in more than $7.5 bil­lion last year. And the com­pa­ny has its own next-gen ther­a­py in the works, as CEO Resh­ma Ke­wal­ra­mani aims to stay one step ahead of the com­pe­ti­tion.

“It’s frankly amaz­ing (and I strug­gle to find an­oth­er ex­am­ple of this) that 1 com­pa­ny (VRTX) has the en­tire $11B CF mod­u­la­tor mar­ket to them­selves but vir­tu­al­ly no com­pe­ti­tion in sight!” Ever­core ISI’s Li­isa Bayko and Jing­ming Chen wrote in a note to in­vestors on Fri­day.

That wasn’t the on­ly blow Ab­b­Vie suf­fered in its Q1 re­sults. Hu­mi­ra — Ab­b­Vie’s star rheuma­toid arthri­tis drug that’s ex­pect­ed to face a slew of gener­ic ri­vals in the US next year — missed sales es­ti­mates in Q1, off­set by biosim­i­lar com­pe­ti­tion in oth­er parts of the world.

The drug brought in $4.7 bil­lion, down 2.7% on a re­port­ed ba­sis. As sev­er­al biosim­i­lar ver­sions pre­pare for US launch­es next year, Ab­b­Vie is de­pend­ing on Skyrizi and Rin­voq to make up for any loss­es.

“We ex­pect com­bined peak sales for Skyrizi and Rin­voq to ex­ceed the peak rev­enues achieved by Hu­mi­ra,” CEO Rick Gon­za­lez said ear­li­er this year, up­on read­ing out the com­pa­ny’s Q4 re­sults.

A num­ber of vari­ables will im­pact the ef­fect of biosim­i­lars on Hu­mi­ra sales, Gon­za­lez said on the call, in­clud­ing pric­ing and avail­abil­i­ty.

“There’s no mar­ket like the Unit­ed States for Hu­mi­ra any­where around the world,” he said. “The Unit­ed States is sig­nif­i­cant­ly larg­er than any oth­er mar­ket around the world. There are cer­tain­ly biosim­i­lar play­ers that are like an Ab­b­Vie, and I would ex­pect them to have man­u­fac­tur­ing ca­pac­i­ty. There are gener­ic play­ers that could have suf­fi­cient man­u­fac­tur­ing ca­pac­i­ty. And then there are very small com­pa­nies.”

Skyrizi, mean­while, brought in $940 mil­lion last quar­ter, up 63.7%. Ex­ecs tout­ed a re­cent launch in pso­ri­at­ic arthri­tis, as well as an up­com­ing de­ci­sion in Crohn’s dis­ease. Rin­voq sales soared 53.6% to $465 mil­lion last quar­ter, but still fell short of sales es­ti­mates.

Jeff Stew­art

“​​We ex­pect growth in the sec­ond-line-plus RA set­ting go­ing for­ward where our field force is now fo­cused on lever­ag­ing com­pelling da­ta from two im­por­tant Phase III tri­als,” said Jeff Stew­art, ex­ec­u­tive VP and chief com­mer­cial of­fi­cer.

In 2019, Ab­b­Vie sealed a $63 bil­lion deal to buy out Al­ler­gan as an­oth­er way to repo­si­tion it­self ahead of the loss of US patent pro­tec­tion for Hu­mi­ra. And ac­cord­ing to the com­pa­ny, it’s now pay­ing off. The aes­thet­ics unit was a key growth dri­ver in Q1, Ab­b­Vie said, with the Botox fran­chise rak­ing in $641 mil­lion.

“Aes­thet­ics is once again ex­ceed­ing ex­pec­ta­tions,” Gon­za­lez said. “The cat­e­go­ry con­tin­ues to grow ro­bust dou­ble dig­its, es­pe­cial­ly in tox­ins and fillers, where there is sub­stan­tial op­por­tu­ni­ty for fur­ther mar­ket pen­e­tra­tion.”

Cor­rec­tion: Ab­b­Vie’s new C2 cor­rec­tor is called ABBV-576

Innoforce is off to the races at its new site in the city of Hangzhou, China.

The Chinese CDMO announced last week that it has started manufacturing at the new facility, which was built to offer process development and manufacturing operations for RNA, plasmid DNA, viral vectors and other cell therapeutics. It will also serve as Innoforce’s corporate HQ.

The company said it’s investing more than $200 million in the 550,000-square-foot manufacturing base for advanced therapies. The GMP manufacturing facility features space for producing plasmids with three 30-liter bioreactors. For viral vector manufacturing, Innoforce also has 200- and 500-liter bioreactors at its disposal, along with eight suites to make cell therapies. The site also includes several labs and warehouse spaces.

As the FDA remains silent on orphan drug exclusivity in the wake of a controversial court case, the agency continues to hand out new designations. The latest: Algernon Pharmaceuticals’ experimental lung disease drug ifenprodil.

The Vancouver-based company announced on Monday that ifenprodil received orphan designation in idiopathic pulmonary fibrosis (IPF), a chronic lung condition that results in scarring of the lungs.  Most IPF patients suffer with a dry cough, and breathing can become difficult.

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.