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.

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