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.


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.

FDA chief Stephen Hahn on Capitol Hill earlier this week (Getty Images)

As FDA buck­les un­der the strain of a pan­dem­ic work­load, Trump again ac­cus­es the agency of a po­lit­i­cal hit job

Peter Marks appeared before a virtual SVB Leerink audience yesterday and said that his staff at FDA’s CBER is on the verge of working around the clock. Manufacturing inspections, policy work and sponsor communications have all been pushed down the to-do list so that they can be responsive to Covid-related interactions. And the agency’s objective right now? “To save as many lives as we can,” Marks said, likening the mortality on the current outbreak as equivalent to “a nuclear bomb on a small city.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Daniel O'Day, Gilead CEO (Kevin Dietsch/UPI/Bloomberg via Getty Images)

Play-by-play of Gilead­'s $21B Im­munomedics buy­out de­tails a fren­zied push — and mints a new biotech bil­lion­aire

Immunomedics had not really been looking for a buyout when the year began. Excited by its BLA for Trodelvy, submitted to the FDA in late 2019, executive chairman Behzad Aghazadeh started off looking for potential licensing deals and zeroed in on four potential partners, including Gilead, following January’s JP Morgan Healthcare Conference in San Francisco. Such talks advanced throughout the year, with discussions advancing to the second round in mid-August.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 90,500+ biopharma pros reading Endpoints daily — and it's free.

President Donald Trump and FDA Commissioner Stephen Hahn (AP Images)

FDA is­sues fi­nal rule al­low­ing im­por­ta­tion of drugs from Cana­da — but al­so keeps the pow­er to re­voke it

Just over a month away from the presidential election, the FDA has issued a final regulation fulfilling President Trump’s promise to let states import certain prescription drugs from Canada.

On Thursday, Trump told a crowd in North Carolina that the new rule goes into effect “today.” But the published regulation states that it won’t take effect for 60 days. And even then, it could be a while before cheaper drugs make it across the border.

President Donald Trump reacts after signing an executive order following his remarks on his healthcare policies yesterday in Charlotte, North Carolina (Getty Images)

Op-ed: Will phar­ma re­al­ly pay for Trump’s lat­est law­less promise to 33 mil­lion Medicare ben­e­fi­cia­ries? Not like­ly

Sitting atop the executive branch, President Donald Trump is the ultimate authority at the FDA. He can fast track any vaccine to approval himself. If it came to that, of course.

What he can’t do is unilaterally order the legislative branch to loosen the Treasury’s coffers for $6.6 billion. Nor can he command pharmaceutical companies to pay for $200 vouchers sent to 33 million Medicare beneficiaries for prescription drugs before the election.

President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the latest incident where Alex Azar has steadfastly taken the side of President Donald Trump over that of the FDA, the HHS secretary was noncommittal this morning when asked if he supports the attempt by his subordinates at the FDA to strengthen guidelines for a vaccine EUA.

Appearing on NBC’s Today Show, the HHS secretary muddied the waters, stating that the guidance that matters is the one that is “actually already out there.”

The win­dow is wide open as four more biotechs join the go-go IPO class of 2020

It’s another day of hauling cash in the biopharma world as four more IPOs priced Friday and a fifth filed its initial paperwork.

The biggest offering comes from PMV Pharma, an oncology biotech focusing on p53 mutations, which raised $211.8 million after pricing shares at $18 apiece. Prelude Therapeutics, developing PRMT5 inhibitors for rare cancers, was next with a $158 million raise, pricing shares at $19 each. Graybug Vision raised $90 million after pricing at $16 per share for its wet AMD candidates, and breast cancer biotech Greenwich Lifesciences brought up the rear with a small, $7 million raise after pricing shares at $5.75.

J&J of­fers PhI/IIa da­ta show­ing its sin­gle-dose vac­cine can stir up suf­fi­cient im­mune re­sponse

Days after J&J dosed the first participants of its Phase III ENSEMBLE trial, the pharma giant has detailed the early-stage data that gave them confidence in a single-dose regimen.

Testing two dose levels either as a single dose or in a two-dose schedule spaced by 56 days in, the scientists from Janssen, the J&J subsidiary developing its vaccine, reported that the low dose induced a similar immune response as the high dose. The interim Phase I/IIa results were posted in a preprint on medRxiv.

New York governor Andrew Cuomo (AP Images)

An­drew Cuo­mo says New York will un­der­take its own vac­cine re­view process, and wouldn’t rec­om­mend trust­ing the fed­er­al gov­ern­ment

The concerns keep mounting over President Donald Trump’s politicization of the FDA and other federal agencies guiding the development of a safe and effective vaccine. And today, the telegenic New York governor Andrew Cuomo appeared to introduce even more politics into the matter — latest in an ongoing series of incidents that have cast the proudly independent FDA in starkly political terms.

During his daily press conference Cuomo said that the state will review any coronavirus vaccines approved by the federal government, citing a lack of trust in the Trump administration. The announcement comes one day after Trump accused the FDA of making an “extremely political” move in proposing stricter vaccine guidance.