Lil­ly, No­vo Nordisk fight in­sulin biosim­i­lars with tweaks to FDA draft guid­ance

As Amer­i­cans with di­a­betes con­tin­ue to die be­cause they can­not af­ford their in­sulin, two of the three in­sulin man­u­fac­tur­ers in the US are do­ing their best to try to al­ter FDA draft guid­ance that seeks to bring more in­sulin com­pe­ti­tion to mar­ket.

The draft guid­ance, un­veiled last No­vem­ber, ex­plains how in­sulin biosim­i­lar de­vel­op­ers may not need to con­duct com­par­a­tive clin­i­cal im­muno­genic­i­ty stud­ies un­der cer­tain cir­cum­stances.

As part of FDA’s rea­son­ing be­hind its sci­en­tif­ic think­ing on a “lack of clin­i­cal im­pact of im­muno­genic­i­ty with in­sulin,” the draft cites a re­vised guide­line from the Eu­ro­pean Med­i­cines Agency in 2015, which said that it no longer rec­om­mends a clin­i­cal im­muno­genic­i­ty study to sup­port a biosim­i­lar mar­ket­ing ap­pli­ca­tion in some cas­es.

FDA al­so points to “decades of clin­i­cal ex­pe­ri­ence with ap­proved in­sulin prod­ucts, in­clud­ing the lack of a cor­re­la­tion be­tween im­muno­genic­i­ty and safe­ty or ef­fec­tive­ness as re­flect­ed in ap­proved prod­uct la­bel­ing for in­sulin prod­ucts.”

But in com­ments sub­mit­ted 28 Jan­u­ary, No­vo Nordisk and Eli Lil­ly do their best to try to main­tain the sta­tus quo and de­lay com­pe­ti­tion from com­ing to mar­ket.

No­vo, for in­stance, said it “ex­pe­ri­enced a cir­cum­stance of un­ex­pect­ed im­muno­genic­i­ty in re­sponse to a new in­sulin ana­log which was en­coun­tered dur­ing its clin­i­cal de­vel­op­ment.”

The com­pa­ny al­so said that its ex­pe­ri­ence “ex­em­pli­fies the un­pre­dictable na­ture of im­muno­genic re­ac­tions in re­sponse to in­sulin for­mu­la­tions. As such, we be­lieve cau­tion needs to be ap­plied re­gard­ing the broad as­sump­tion” in the draft guid­ance that says that “if a com­par­a­tive an­a­lyt­i­cal as­sess­ment based on state-of-the-art tech­nol­o­gy sup­ports a demon­stra­tion of ‘high­ly sim­i­lar’ for a pro­posed biosim­i­lar or in­ter­change­able in­sulin prod­uct, there would be lit­tle or no resid­ual un­cer­tain­ty re­gard­ing im­muno­genic­i­ty.”

Lil­ly, mean­while, said that FDA should re­vise the guid­ance to ex­plain which biosim­i­lar ap­pli­ca­tions this im­muno­genic­i­ty test­ing pol­i­cy ap­plies to.

“Should FDA in­tend to ap­ply the Draft Guid­ance to in­sulin prod­ucts which were not ap­proved un­der a sec­tion 505(b)(2) ap­pli­ca­tion, Lil­ly be­lieves that good sci­ence dic­tates some amount of clin­i­cal im­muno­genci­ty da­ta should be re­quired in or­der to un­der­stand the im­pact of po­ten­tial dif­fer­ences in im­muno­genic­i­ty pro­files on clin­i­cal out­comes,” Lil­ly said.

The com­pa­ny al­so wants FDA to re­vise the guid­ance to note that it does not ad­dress is­sues with re­spect to prod­uct biosim­i­lar­i­ty and in­ter­change­abil­i­ty of de­liv­ery de­vices and pre­sen­ta­tions, in­clud­ing con­nect­ed sys­tems.

And Lil­ly laid out its case for why in­sulin biosim­i­lars should not be ap­proved as in­ter­change­able prod­ucts.

“Al­though pre­sen­ta­tion con­sid­er­a­tions are im­por­tant for biosim­i­lar­i­ty as­sess­ments, FDA should pay par­tic­u­lar at­ten­tion to the in­sulin prod­ucts pre­sen­ta­tions in the in­ter­change­abil­i­ty con­text. There, by virtue of au­to­mat­ic sub­sti­tu­tion based on an in­ter­change­abil­i­ty des­ig­na­tion, a pa­tient could be con­front­ed with an un­fa­mil­iar pre­sen­ta­tion with­out the ben­e­fit of pre­scriber over­sight or ad­di­tion­al train­ing,” Lil­ly added.

The oth­er in­sulin man­u­fac­tur­er serv­ing the US, Sanofi, did not sub­mit a com­ment on the draft guid­ance, ac­cord­ing to the dock­et.

All three have raised their prices sig­nif­i­cant­ly over the past decade. For in­stance, in 2012, a vial of Lil­ly’s Hu­ma­log in­sulin was priced at $130, and by 2016, the same vial was priced at $255.

Both Lil­ly and No­vo have launched au­tho­rized gener­ics ver­sions of their in­sulin prod­ucts at re­duced prices in prepa­ra­tion for biosim­i­lar com­pe­ti­tion. But an in­ves­ti­ga­tion from Sens. Eliz­a­beth War­ren (D-MA) and Richard Blu­men­thal (D-CT) found that Lil­ly’s au­tho­rized gener­ic was wide­ly un­avail­able in phar­ma­cies.

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