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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What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

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After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

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Lat­est news: It’s a no on uni­ver­sal boost­ers; Pa­tient death stuns gene ther­a­py field; In­side Tril­li­um’s $2.3B turn­around; 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.

Next week is shaping up to be a busy one, as our editor-in-chief John Carroll and managing editor Kyle Blankenship lead back-to-back discussions with a great group of experts to discuss the weekend news and trends. John will be spending 30 minutes with Jake Van Naarden, the CEO of Lilly Oncology, and Kyle has a brilliant panel lined up: Harvard’s Cigall Kadoch, Susan Galbraith, the new head of cancer R&D at AstraZeneca, Roy Baynes at Merck, and James Christensen at Mirati. Don’t miss out on the action — sign up here.

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With Amgen already providing proof-of-concept for KRAS inhibitors with its sotorasib, Mirati Therapeutics is piecing together a follow-up effort in lung cancer with data it thinks are superior. But in colon cancer, where solo sotorasib has turned in a dud, Mirati may now have a strong case for superiority.

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President Biden and Pfizer CEO Albert Bourla (Patrick Semansky/AP Images)

Chaot­ic ad­comm sees Pfiz­er/BioN­Tech boost­ers re­ject­ed for gen­er­al pop­u­la­tion, but rec­om­mend­ed for old­er and high-risk pop­u­la­tions

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Merck Research Laboratories CMO Roy Baynes

Mer­ck­'s Keytru­da un­corks full da­ta on lat­est ad­ju­vant win — this time in melanoma — adding bricks to ear­ly can­cer wall

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