Eli Lil­ly notch­es an­oth­er pos­i­tive baric­i­tinib eczema tri­al, but has Der­mi­ra made it ob­so­lete?

En­ter­ing to­day, most of what you need­ed to know about Eli Lil­ly’s JAK in­hibitor baric­i­tinib could be found in two places:

In the FDA-man­dat­ed, 1,000-plus word, bold­ed note now ap­pend­ed to the end of every press re­lease about the drug that be­gins: “WARN­ING: SE­RI­OUS IN­FEC­TIONS, MA­LIG­NAN­CY, AND THROM­BO­SIS.”

And in the run-up to the JP Mor­gan Health­care Con­fer­ence, when Eli Lil­ly dropped $1.1 bil­lion on the an­ti-in­flam­ma­to­ry skin biotech Der­mi­ra – a move that SVB Leerink’s Pasha Sar­raf had pre­dict­ed a month pri­or based on the con­sis­tent­ly meh re­sults baric­i­tinib had pro­duced in Phase III tri­als.

To­day, though, Eli Lil­ly an­nounced pos­i­tive re­sults from a fifth tri­al. The pri­ma­ry end­point was the per­cent­age of atopic der­mati­tis (AD) pa­tients who saw a 75% change in their Eczema Area and Sever­i­ty In­dex (EASI), and it showed a far high­er per­cent­age of pa­tients reached that lev­el on the drug arms than on the place­bo arm. For the high­est dose of the drug, that was 29.5%, com­pared with 8.2%.

Those re­sults are an im­prove­ment over the first Phase III tri­als an­nounced ear­li­er this year, when the same 2-mil­ligram dose scored around 18%. But it is still be­hind the da­ta Pfiz­er’s JAK in­hibitor abroc­i­tinib has post­ed on the same end­points. And it is line with the Phase III re­sults for a baric­i­tinib com­bi­na­tion treat­ment an­nounced in Au­gust, a few months be­fore Sar­raf wrote a damn­ing note about the drug and pre­dict­ed Eli Lil­ly would ac­quire Der­mi­ra.

“Nei­ther we, nor any of the KOLs with whom we have spo­ken be­lieves that bari’s pro­file is sur­viv­able com­mer­cial­ly in AD,” she wrote to in­vestors on De­cem­ber 9.

Af­ter near­ly a decade of co-de­vel­op­ing the drug with In­cyte, Lil­ly won ap­proval for rheuma­toid arthri­tis in the sum­mer of 2018. But it came, like oth­er JAK in­hibitors, with a black box warn­ing and strict lim­its on dos­ing, con­di­tions the FDA made af­ter ini­tial­ly re­ject­ing the drug. It al­so didn’t look more ef­fec­tive than its ri­vals. Sales were ane­mic and In­cyte washed its hands of the drug. Eli Lil­ly kept the tri­als go­ing.

Eli Lil­ly has said the tri­als sup­port an ap­pli­ca­tion for AD ap­proval, but will an­oth­er 10 per­cent­age points on one end­point, in one study be enough to make the drug com­pet­i­tive? The com­pa­ny doesn’t seem to be bet­ting on it. Der­mi­ra, the new ac­qui­si­tion, is fo­cused on le­brik­izum­ab, an an­ti-in­flam­ma­to­ry that got 56% of pa­tients to achieve the bench­mark 75% change in EASI score in a Phase IIb tri­al, plus good re­sults on an­oth­er AD end­point: skin le­sion clear­ing.

Eli Lil­ly won’t be alone in that race ei­ther. They’ll be chas­ing Re­gen­eron and Sanofi’s Dupix­ent, which is ap­proved and has post­ed sim­i­lar num­bers.

And both of those drugs have an ad­van­tage on baric­i­tinib and abroc­i­tinib. They’re IL-13 in­hibitors, not JAKs (Dupix­ent al­so hits IL-4). And at min­i­mum, that should mean a lot few­er bold­ed, all-caps let­ters in press re­leas­es and on the la­bel.

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

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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.

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.

Mer­ck flesh­es out Keytru­da win in first-line cer­vi­cal can­cer, adding more fire­pow­er to its ear­ly can­cer push

Merck has worked hard to bring its I/O blockbuster Keytruda into earlier and earlier lines of therapy, and now the wonder drug appears poised to make a quick entry into early advanced cervical cancer.

A combination of Keytruda and chemotherapy with or without Roche’s Avastin cut the risk of death by 33% over chemo with or without Avastin (p=<0.001) in first-line patients with persistent, recurrent or metastatic cervical cancer, according to full data from the Phase III KEYNOTE-826 study presented Saturday at #ESMO21.

EQRx chairman Alexis Borisy and CEO Melanie Nallichieri

EQRx, CStone un­furl full lung can­cer da­ta for PD-L1 drug in what the part­ners are call­ing a first

As a self-stylized drug pricing disruptor, EQRx has high hopes for its lead PD-(L)1 to offer proof of concept for the entire business model. After touting a win back in May, the biotech is back with full data in lung cancer that could back up an approval.

Patients dosed with EQRx and CStone Pharmaceuticals’ sugemalimab posted median progression-free survival of 9 months compared with 5.8 months for patients given placebo (p=0.0026), according to full data from the Phase III GEMSTONE-301 study in Stage III non-small cell lung cancer set to be presented at this weekend’s #ESMO21.

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As­traZeneca touts Imfinzi im­munother­a­py com­bos for lung can­cer in push to dri­ve PD-L1 drug up­take

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an Innate’s anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.