FDA (via Endpoints News)

FDA tar­gets faster re­views for biosim­i­lar sup­ple­ments, draft guid­ance says

The FDA  on Thurs­day pub­lished new draft guid­ance ex­plain­ing how it will speed its re­view of biosim­i­lar or in­ter­change­able ap­pli­ca­tion sup­ple­ments, which can be used to up­date the ini­tial biosim­i­lar ap­proval when it is for few­er than all the ref­er­ence prod­uct’s li­censed con­di­tions of use.

The 9-page draft de­tails how FDA can­not li­cense a biosim­i­lar or in­ter­change­able prod­uct for an in­di­ca­tion pro­tect­ed by or­phan-drug ex­clu­siv­i­ty or pe­di­atric ex­clu­siv­i­ty un­til the ex­pi­ra­tion of that ex­clu­siv­i­ty. Ap­pli­cants al­so may de­cide not to seek li­cen­sure of a pro­posed biosim­i­lar or pro­posed in­ter­change­able prod­uct for con­di­tions of use that are pro­tect­ed by a patent or for oth­er rea­sons.

For in­stance, when Pfiz­er’s In­flec­tra (in­flix­imab-dyyb) and Mer­ck’s Ren­flex­is (in­flix­imab-ab­da) were first ap­proved, FDA ap­proved them for all the same in­di­ca­tions as J&J’s Rem­i­cade (in­flix­imab), ex­cept pe­di­atric ul­cer­a­tive col­i­tis. This in­di­ca­tion was ex­clud­ed be­cause J&J at the time en­joyed an FDA-grant­ed pe­ri­od of or­phan ex­clu­siv­i­ty. Sim­i­lar­ly, when Am­gen won ap­proval for its Hu­mi­ra (adal­i­mum­ab) biosim­i­lar Am­je­vi­ta (adal­i­mum­ab-at­to), the com­pa­ny did not seek ap­proval for sev­er­al in­di­ca­tions be­cause of or­phan ex­clu­siv­i­ty.

But af­ter that ex­clu­siv­i­ty or patent ex­pires, an ap­pli­cant may de­cide to sub­mit a sup­ple­ment to the li­censed 351(k) bi­o­log­ics li­cense ap­pli­ca­tion (BLA) for the pre­vi­ous­ly pro­tect­ed in­di­ca­tion.

And al­though FDA com­mit­ted to re­view­ing and act­ing on orig­i­nal 351(k) BLA sup­ple­ments with clin­i­cal da­ta with­in 10 months of re­ceipt, the agency now says such sup­ple­ments will be re­viewed and act­ed up­on in a 6-month time­frame.

“As not­ed, the Bs­U­FA II Goals Let­ter de­scribes a 10-month goal date for orig­i­nal 351(k) BLA sup­ple­ments with clin­i­cal da­ta. How­ev­er, at this time, FDA be­lieves that a re­view time­frame of 6 months will gen­er­al­ly be ap­pro­pri­ate for a sup­ple­ment to a li­censed 351(k) BLA seek­ing li­cen­sure of the biosim­i­lar or in­ter­change­able prod­uct for an ad­di­tion­al con­di­tion of use that has been pre­vi­ous­ly li­censed for the ref­er­ence prod­uct, as­sum­ing the sup­ple­ment does not raise nov­el re­view is­sues,” the draft says.

If an ap­pli­cant does not want FDA to take ac­tion on a 351(k) BLA or sup­ple­ment be­fore a spec­i­fied date, the ap­pli­cant should re­quest that FDA re­frain from act­ing on the ap­pli­ca­tion, the draft adds.

To make such a re­quest, the draft says that an ap­pli­cant should in­clude the fol­low­ing lan­guage on the cov­er let­ter of their BLA or sup­ple­ment, in bold type­face and promi­nent­ly placed above the body of the cov­er let­ter:

351(k) BLA ac­tion tim­ing re­quest: [Ap­pli­cant Name] re­quests that FDA not take ac­tion on this [ap­pli­ca­tion/sup­ple­ment] be­fore [spec­i­fied date].

The draft al­so ex­plains how the pro­posed la­bel­ing for a biosim­i­lar will de­pend on whether the ap­pli­cant is seek­ing li­cen­sure for all (or few­er) of the con­di­tions of use li­censed for the ref­er­ence prod­uct. And an ap­pli­cant may sub­mit a jus­ti­fi­ca­tion as to why, in the ap­pli­cant’s view, the draft la­bel­ing meets the re­quire­ments for ap­proval, con­sid­er­ing the con­di­tions of use for which the ap­pli­cant is seek­ing li­cen­sure.

FDA al­so says that it rec­om­mends that an ap­pli­cant seek­ing li­cen­sure for a pro­posed in­ter­change­able prod­uct seek li­cen­sure for all of the ref­er­ence prod­uct’s li­censed con­di­tions of use when pos­si­ble.

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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.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

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.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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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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Mi­rati's KRAS drug looks like the fa­vorite in colon can­cer with new da­ta, putting the pres­sure square on Am­gen

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.

Mirati’s adagrasib, dosed solo or in combination with chemotherapy cetuximab, showed response rates grater than sotorasib solo  and as part of combination study in a similar patient population also revealed this week at #ESMO21. Mirati’s data were presented as part of a cohort update from the Phase II KRYSTAL-1 study testing adagrasib in a range of solid tumors harboring the KRAS-G12C mutation.

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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

With just days before President Joe Biden’s Covid-19 booster rollout is set to go into effect, an FDA advisory committee appeared on the verge of not recommending boosters for anyone in the US before a last-minute change of wording laid the groundwork for older adults to have access to a third dose.

The FDA’s adcomm on Vaccines and Related Biological Products (VRBPAC) roundly rejected Pfizer/BioNTech booster shots for all individuals older than 16 by a 16-2 vote Friday afternoon. Soon after, however, the agency posed committee members a new question limiting booster use to the 65-and-older population and individuals at high risk of disease due to occupational exposure or comorbidities.

The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ESMO Congress has had a major focus on Big Pharma drugs — most notably candidates from Merck and AstraZeneca — but there have also been updates from smaller biotechs with data looking to challenge the big-name drugmakers.

Today, we’re highlighting some of the data releases that flew under the radar at #ESMO21 — whether from early-stage drugs looking to make a mark or older stalwarts with interesting follow-up data.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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

In recent months, the battle for PD-(L)1 dominance has spilled over into early cancer with Merck’s Keytruda and Bristol Myers Squibb’s Opdivo all alone on the front lines. Keytruda now has another shell in its bandolier, and it could spell a quick approval.

Keytruda cut the risk of relapse or death by 35% over placebo (p=0.00658) in high-risk, stage 2 melanoma patients who had previously undergone surgery to remove their tumors, according to full data from the Phase III KEYNOTE-716 presented Saturday at #ESMO21.

Take­da scores a win for a rare type of lung can­cer, gear­ing up for a show­down with J&J

Four months after J&J’s infused drug Rybrevant scored the industry’s first win in a rare type of non-small cell lung cancer (NSCLC), Takeda is following up with an oral option for the small but desperate patient population.

The FDA granted an accelerated approval to Takeda’s oral TKI inhibitor Exkivity (mobocertinib) in metastatic NSCLC patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, the company announced on Wednesday.

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