Photo credit: Jacquelyn Martin

Where are the in­ter­change­able biosim­i­lars?

In June 2017, Leah Christl, for­mer biosim­i­lar lead at FDA, told a con­fer­ence in Chica­go that in­ter­change­able biosim­i­lars were like­ly com­ing to the US mar­ket with­in two years.

And al­though no in­ter­change­able biosim­i­lar has been ap­proved by FDA yet, and Christl has since moved on to Am­gen, progress on in­ter­change­able biosim­i­lars has been slow in the in­ter­ven­ing years.

Most re­cent­ly, Boehringer In­gel­heim an­nounced that it has com­plet­ed, as of last April, a switch­ing study nec­es­sary for launch­ing an in­ter­change­able biosim­i­lar for Hu­mi­ra (adal­i­mum­ab), al­though the com­pa­ny did not of­fer any fur­ther de­tails on the tim­ing of its sub­mis­sion to FDA or whether there will be an ad­vi­so­ry com­mit­tee to re­view the da­ta. Boehringer al­ready has an adal­i­mum­ab biosim­i­lar ap­proved by FDA, which it will launch in the US on 1 Ju­ly 2023.

In ad­di­tion, next March, in­sulin prod­ucts will make the tran­si­tion from be­ing reg­u­lat­ed un­der the FD&C Act to the PHS Act, which, ac­cord­ing to for­mer FDA Com­mis­sion­er Scott Got­tlieb means in­ter­change­able in­sulin prod­ucts are like­ly com­ing. FDA held a meet­ing in May on in­ter­change­able in­sulins, which will be par­tic­u­lar­ly im­por­tant as on­ly three fol­low-on in­sulin prod­ucts — Basaglar, Lus­duna and Ad­mel­og — have been ap­proved since 2015.

But out­side of the one po­ten­tial adal­i­mum­ab in­ter­change­able and sev­er­al pos­si­ble in­sulin in­ter­change­able prod­ucts (none of which have been pub­licly dis­closed), no oth­er com­pa­nies have even dis­closed be­gin­ning a switch­ing study. And al­though how such switch­ing stud­ies nec­es­sary for achiev­ing this des­ig­na­tion was on­ly fi­nal­ized last May, with FDA’s guid­ance on biosim­i­lar in­ter­change­abil­i­ty, com­pa­nies have known about the switch­ing study re­quire­ments since at least when the draft was re­leased in Jan­u­ary 2017.

Bern­stein an­a­lyst Ron­ny Gal told Fo­cus via email that Am­gen and San­doz have said they will pur­sue in­ter­change­able biosim­i­lars but switch­ing stud­ies have not list­ed yet.

Got­tlieb al­so said re­cent­ly in an in­ter­view that he be­lieves the use of switch­ing stud­ies to get an in­ter­change­abil­i­ty claim “is fair­ly ef­fi­cient, but I think there’s things that you can con­tin­ue to look at in terms of us­ing re­al-world ev­i­dence [RWE] and look­ing at how you struc­ture those switch­ing stud­ies to po­ten­tial­ly make it more ef­fi­cient.”

An­tho­ny Maf­fia, head of reg­u­la­to­ry af­fairs, North Amer­i­ca at San­doz, told Fo­cus in a phone in­ter­view that he agrees with Got­tlieb on the pos­si­ble use of RWE, “but the way it’s ap­plied needs flush­ing out.”

He al­so said he thinks the in­ter­change­abil­i­ty des­ig­na­tion is “cre­at­ing an ad­di­tion­al bar­ri­er to ac­cess, and we keep em­pha­siz­ing that and feel strong­ly that it’s unique to the US and sets us apart from oth­er glob­al health au­thor­i­ties.”

A lot of the dis­cus­sion on the sav­ings from biosim­i­lars is al­so cen­tered on the fact that state phar­ma­cy laws (45 states and Puer­to Ri­co have passed leg­is­la­tion, ac­cord­ing to Am­gen) stip­u­late that biosim­i­lars may on­ly be sub­sti­tut­ed at the phar­ma­cy if FDA has des­ig­nat­ed them as in­ter­change­able to their ref­er­ence prod­ucts.

“Un­less and un­til we change the way we pay for drugs more broad­ly, in­ter­change­ables are re­al­ly the cen­tral path to re­al com­pe­ti­tion and low­er prices,” Aaron Kessel­heim, di­rec­tor of the Pro­gram on Reg­u­la­tion, Ther­a­peu­tics and Law at Brigham and Women’s Hos­pi­tal, Har­vard Med­ical School, pre­vi­ous­ly ex­plained to Fo­cus.

But many bi­o­log­ics are ad­min­is­tered by physi­cians so the in­ter­change­abil­i­ty des­ig­na­tion will like­ly not be pur­sued in those in­stances. Oth­ers al­so have said in­ter­change­ables will not nec­es­sar­i­ly hit the mar­ket with as large of a dis­count as biosim­i­lars with­out the des­ig­na­tion.

In ad­di­tion, there is a lot of room for mis­in­for­ma­tion among phar­ma­cists and doc­tors. Hil­lel Co­hen, ex­ec­u­tive di­rec­tor of sci­en­tif­ic af­fairs at San­doz, pre­vi­ous­ly ex­plained how an in­ter­change­able biosim­i­lar is not more high­ly sim­i­lar than a non-in­ter­change­able biosim­i­lar, al­though the des­ig­na­tion may pro­vide the false per­cep­tion of a bet­ter prod­uct.

Maf­fia added that he thinks FDA “ab­solute­ly” must clar­i­fy when cer­tain com­pa­nies are spread­ing mis­in­for­ma­tion on biosim­i­lars. “We have to get to a com­mon set of lan­guage and that’s some­thing that FDA has a role in,” he said.


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Lat­est on ul­tra-rare dis­ease ap­proval; Pos­i­tive, if mixed, signs for Bio­gen's ALS drug; Clay Sie­gall finds a new job; 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.

Over the last four years, we’ve honored 80 women whose extraordinary accomplishments have changed the game in biopharma R&D. You can now nominate someone to be highlighted in this year’s special report. Details are here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA spells out how can­cer drug de­vel­op­ers can use one tri­al for both ac­cel­er­at­ed and full ap­provals

The FDA’s Oncology Center of Excellence has been a bright spot within the agency in terms of speeding new treatments to patients. That flexibility was on full display this morning as FDA released new draft guidance spelling out exactly how oncology drug developers can fulfill both the accelerated and full approval’s requirements with just a single randomized controlled trial.

While Congress recently passed legislation that will allow FDA to require confirmatory trials to be recruiting and ongoing prior to granting an accelerated approval, the agency is now making clear that the initial trial used to win the AA, if designed appropriately, can also serve as the trial for converting the accelerated approval into a full approval.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

Eu­ro­pean Com­mis­sion de­lays pro­pos­al for ma­jor changes to phar­ma leg­is­la­tion

The European Commission has once again delayed the release of its proposal for an overhaul of the continent’s pharmaceutical legislation.

The release, previously anticipated on March 29, will occur “slightly later” than expected due to the “very busy College agendas of the last few weeks,” a Commission spokesperson told Endpoints News via email.

While the agency hasn’t provided an updated timeline, the spokesperson said the agenda is “always indicative and adoption dates of Commission proposals may change any time, especially when these proposals concern reforms of complex legislations of major importance.”

In­cyte wins ac­cel­er­at­ed ap­proval for PD-1 in rare skin can­cer

Incyte touted an accelerated approval for its PD-1 retifanlimab in a rare skin cancer on Wednesday, roughly a year and a half after the drug suffered a rejection in squamous cell carcinoma of the anal canal (SCAC).

Retifanlimab, marketed as Zynyz, was approved for metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), a fast-growing skin cancer typically characterized by a single, painless nodule. It’s roughly 40 times rarer than melanoma, according to the nonprofit Skin Cancer Foundation — but incidence is growing, particularly among older adults, Incyte said in its announcement.

FDA re­jects Ab­b­Vie's in­fu­sion ther­a­py for Parkin­son's, re­quests more in­fo on pump de­vice

The FDA rejected AbbVie’s 24-hour infusion therapy for Parkinson’s, saying it needs more information on a device used to administer the treatment before it can clear it.

The Chicago-area drugmaker said in a press release that the complete response letter from the agency didn’t include any requests for more efficacy or safety trials related to the drug, known as ABBV-951. The company said it aims to “resubmit the NDA as soon as possible.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,600+ biopharma pros reading Endpoints daily — and it's free.

FDA+ roundup: Leg­isla­tive asks for 2024 fo­cus on more au­thor­i­ties, gener­ic drug com­pe­ti­tion

The FDA’s legislative priorities for the next year highlight the agency’s focus on expanding generic drug competition, backstopping the supply chain and growing its current authorities.

On the new authorities front, FDA is seeking to expand its mandatory recall authority for all drugs, as the agency has been embroiled in a long process to remove some from the market. Covis Pharma refused to pull its preterm birth drug Makena, which won accelerated approval, for almost five years after failing its confirmatory trial. The company has since reversed course after a negative adcomm.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.