UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Fri­day award­ed Boehringer In­gel­heim the first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra biosim­i­lar Cyl­te­zo, mean­ing that when it launch­es in Ju­ly 2023, phar­ma­cists will be able to au­to­mat­i­cal­ly sub­sti­tute the Boehringer’s ver­sion for Ab­b­Vie’s mega-block­buster with­out a doc­tor’s in­put.

The des­ig­na­tion will like­ly give Boehringer, which first won ap­proval for Cyl­te­zo in 2017, the leg up on a crowd­ed field of Hu­mi­ra com­peti­tors.

The field’s cur­rent fron­trun­ner is Am­gen’s Am­je­vi­ta (adal­i­mum­ab-at­to), which is like­ly to launch in Jan­u­ary 2023, al­though oth­ers have won ap­provals and will hit the mar­ket lat­er in 2023, in­clud­ing San­doz’s Hy­ri­moz (adal­i­mum­ab-adaz), Pfiz­er’s Abri­la­da (adal­i­mum­ab-afzb) and Sam­sung’s Hadli­ma (adal­i­mum­ab-bwwd). Oth­ers from Fre­se­nius Kabi, Co­herus and Mo­men­ta may be com­ing too, pend­ing ap­proval.

Ex­perts will be keen to see which com­peti­tors take the largest share of Hu­mi­ra’s $15B+ an­nu­al mar­ket, and how low the price drops. Five Hu­mi­ra biosim­i­lars are cur­rent­ly mar­ket­ed in Eu­rope, and the price has de­clined by more than 50%, al­though lat­er en­trants have trou­ble grab­bing mar­ket share, ac­cord­ing to Bern­stein biotech an­a­lyst Ron­ny Gal.

But un­like the US, Eu­rope does not use an in­ter­change­abil­i­ty des­ig­na­tion, so all of the com­peti­tors can be used in­ter­change­ably with the ref­er­ence prod­uct. This would seem to sug­gest that Boehringer would have a ma­jor jump on the field, but some ex­perts claim that Cyl­te­zo and oth­er Hu­mi­ra biosim­i­lars are ap­proved for a con­cen­tra­tion of the ref­er­ence prod­uct that peo­ple no longer use.

“From my pay­er dis­cus­sion it’s a nice-to-have,” Gal told End­points. “All else be­ing equal, hav­ing both for­mu­la­tions will be an ad­van­tage.”

An­oth­er po­ten­tial Hu­mi­ra com­peti­tor from Alvotech is al­so seek­ing an in­ter­change­abil­i­ty des­ig­na­tion for its biosim­i­lar, which has yet to be FDA ap­proved. The com­pa­ny is still locked in a court bat­tle with Ab­b­Vie, but re­cent­ly had an Ab­b­Vie suit thrown out. Alvotech claims to be de­vel­op­ing the first in­ter­change­able biosim­i­lar for the high­er con­cen­tra­tion of Hu­mi­ra, which is much more wide­ly used now than when the oth­er biosim­i­lars first won FDA ap­proval back in Sep­tem­ber 2016.

“So when those biosim­i­lar com­pa­nies en­ter in 2023, we ex­pect that on­ly 10% of Hu­mi­ra sales in the US – around 15 to 16 bil­lion, on­ly 10% will be [the low­er con­cen­tra­tion] 50 mg. We, on the oth­er hand, were the first to get fil­ing ac­cep­tance [with the FDA] of the high­er con­cen­tra­tion, so we can fo­cus on 90% of the mar­ket when we come out,” Alvotech CEO Róbert Wess­man pre­vi­ous­ly told End­points News.

Boehringer pe­ti­tioned the FDA back in 2020 over the agency’s in­ter­pre­ta­tion of the term “strength,” not­ing that un­der FDA’s cur­rent in­ter­pre­ta­tion, no cur­rent­ly ap­proved adal­i­mum­ab prod­uct can be con­sid­ered biosim­i­lar or in­ter­change­able to Hu­mi­ra’s high­er con­cen­tra­tion for­mu­la­tion be­cause the prod­ucts have dif­fer­ent con­cen­tra­tions.

Cyl­te­zo is ap­proved in two strengths – 20 mg and 40 mg – in a 50 mg/mL con­cen­tra­tion for­mu­la­tion that is cit­rate-free, and five oth­er adal­i­mum­ab biosim­i­lars have been ap­proved on­ly as a 50 mg/mL con­cen­tra­tion for­mu­la­tion.

“In Boehringer In­gel­heim’s view, these biosim­i­lar prod­ucts, in­clud­ing Cyl­te­zo, should be con­sid­ered to have the same ‘strength’ as the cor­re­spond­ing OC [orig­i­nal con­cen­tra­tion] and HC [high­er con­cen­tra­tion] ver­sions of Hu­mi­ra be­cause they con­tain the same to­tal drug con­tent per con­tain­er (e.g., 40 mg), re­gard­less of the vol­ume of ex­cip­i­ents. This in­ter­pre­ta­tion of ‘strength’ would give spon­sors of adal­i­mum­ab prod­ucts with OC for­mu­la­tions, like Cyl­te­zo, the op­por­tu­ni­ty to sub­mit a sec­tion 351(k)ap­pli­ca­tion seek­ing biosim­i­lar­i­ty and/or in­ter­change­abil­i­ty de­ter­mi­na­tions that ap­ply to Hu­mi­ra’s HC for­mu­la­tion.”

A biosim­i­lar ex­pert who re­quest­ed anonymi­ty not­ed that this ap­proval for the Cyl­te­zo in­ter­change­able may be a sign that the FDA would al­so OK Boehringer’s cit­i­zen pe­ti­tion, but the dock­et has yet to be up­dat­ed with a fi­nal re­sponse from FDA.

A Boehringer spokesper­son told End­points in a state­ment, “We re­main com­mit­ted to mak­ing Cyl­te­zo com­mer­cial­ly avail­able as an In­ter­change­able biosim­i­lar with Hu­mi­ra in 2023 and will con­tin­ue to work with them to re­solve ques­tions posed in our Cit­i­zen Pe­ti­tion. You are prob­a­bly al­ready aware that the FDA will al­so be hold­ing a vir­tu­al pub­lic meet­ing to dis­cuss pro­posed rec­om­men­da­tions for the reau­tho­riza­tion of the Biosim­i­lar User Fee Act (Bs­U­FA) lat­er this year. Giv­en the com­plex­i­ty of this top­ic, we are en­cour­aged to see ad­di­tion­al fo­cus on ap­pro­pri­ate fund­ing of biosim­i­lar de­vel­op­ment.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

All about Omi­cron; We need more Covid an­tivi­rals; GSK snags Pfiz­er’s vac­cine ex­ec; Janet Wood­cock’s fu­ture at FDA; 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.

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Usama Malik

Ex-Im­munomedics CFO charged with in­sid­er trad­ing, faces up to 20 years in prison af­ter al­leged­ly tip­ping off girl­friend and rel­a­tives of a PhI­II suc­cess

The former CFO of Immunomedics, who helped steer the company to its $21 billion buyout by Gilead last year, has been charged with insider trading, the Department of Justice announced Thursday.

Usama Malik tipped off his then-girlfriend and four others that a Phase III study for Trodelvy would be stopped early four days before Immunomedics publicly announced the result in April 2020, DoJ alleged in its complaint. The individuals then purchased Immunomedics shares, selling them after the news broke and Immunomedics’ stock price doubled.

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Merck's new antiviral molnupiravir (Quality Stock Arts / Shutterstock)

As Omi­cron spread looms, oral an­tivi­rals ap­pear to be one of the best de­fens­es — now we just need more

After South African scientists reported a new Covid-19 variant — dubbed Omicron by the WHO — scientists became concerned about how effective vaccines and monoclonal antibodies might be against it, which has more than 30 mutations in the spike protein.

“I think it is super worrisome,” Dartmouth professor and Adagio co-founder and CEO Tillman Gerngross told Endpoints News this weekend. Moderna CEO Stéphane Bancel echoed similar concerns, telling the Financial Times that experts warned him, “This is not going to be good.”

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Pfiz­er, Am­gen and Janssen seek fur­ther clar­i­ty on FDA's new ben­e­fit-risk guid­ance

Three top biopharma companies are seeking more details from the FDA on how the agency conducts its benefit-risk assessments for new drugs and biologics.

While Pfizer, Amgen and Janssen praised the agency for further spelling out its thinking on the subject in a new draft guidance, including a discussion of patient experience data as part of the assessment, the companies said the FDA could’ve included more specifics in the 20-page draft document.

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Janet Woodcock (AP Images)

Janet Wood­cock plots her fu­ture at FDA, with se­nior ad­vi­sor role to fall back on if Califf wins con­fir­ma­tion

Acting FDA commissioner Janet Woodcock has been the face of just about every drug approval decision at the agency since the turn of the century. Since the pandemic began, she’s moved between the top of the drugs center to the head of therapeutics at Operation Warp Speed, leading the drive for work on Covid-targeted mAbs and antivirals.

Looking forward — and pending a quick Senate confirmation to cement Rob Califf’s return to the top of FDA early next year — Woodcock’s role at the agency will again be in flux.

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Richard Pazdur (via AACR)

Ac­cel­er­at­ed ap­proval re­forms need mean­ing­ful con­fir­ma­to­ry tri­al im­prove­ments, pro­fes­sors write in Sci­ence

Outside of Covid-19, 2021 has been the year of the accelerated approval.

Beginning last spring, FDA openly challenged six “dangling” accelerated approvals (hadn’t confirmed their clinical benefit yet), three of which were later pulled by the companies.

Then in June, FDA pulled out the accelerated approval pathway, seemingly out of nowhere, to sign off on Biogen’s controversial Alzheimer’s drug Aduhelm. It hadn’t even been mentioned at the drug’s adcomm.

Common performs onstage, December 2020 (Getty Images)

Com­mon, Jamie Foxx among celebs stand­ing up for clin­i­cal tri­als in star-stud­ded can­cer group's pan­dem­ic push

Healthcare screenings and clinical trial enrollment were battered by the pandemic. But the well-known celebrity-backed Stand Up To Cancer non-profit, along with pharma and advocacy partners, has been working to reverse that and make up lost ground, by stepping up awareness campaigns.

Twelve campaigns launched in 2020 and another five in 2021 amplify the need for cancer screening and care, especially for underserved communities. While pharma companies have long been donors to the cancer research group, Covid brought new support — and increased awareness efforts.

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UP­DAT­ED: Am­gen halts some drug dis­counts for safe­ty net hos­pi­tals as SCO­TUS takes on 340B case

Amgen will soon be the 10th biopharma company to pull back on offering drug discounts to contract pharmacies of safety-net hospitals under a federal program. Like its peers, Amgen argues that the growth of these contract pharmacies has ballooned in recent years and needs to be reigned in.

Beginning Jan. 3, 2022, Amgen’s policy will only allow 340B covered hospitals to designate a single pharmacy location, with the exception of federal grantees and contract pharmacies wholly owned by a 340B hospital, or that have common ownership with a health system.