Olu­mi­ant from Lil­ly, In­cyte clears third eczema study, but who will use it?

Months ago In­cyte $IN­CY elect­ed to stop fund­ing the de­vel­op­ment of Olu­mi­ant (baric­i­tinib) — com­ing up with those funds be­came part­ner Eli Lil­ly’s prob­lem. The JAK in­hibitor, which has been dogged by safe­ty con­cerns, has now cleared an­oth­er late-stage atopic der­mati­tis (AD) study.

In June 2018, the FDA ap­proved on­ly the small 2 mg dose of the drug for rheuma­toid arthri­tis, with a black box warn­ing high­light­ing the ther­a­py’s side ef­fects, in­clud­ing a star­tling throm­boem­bolism sig­nal, quash­ing Lil­ly’s $LLY block­buster dreams. The agency had ini­tial­ly re­ject­ed the drug, de­mand­ing a new study, but un­der the lead­er­ship of (now for­mer) FDA com­mis­sion­er Scott Got­tlieb, the FDA had an in­ex­plic­a­ble change of heart, and al­lowed the mar­ket­ing ap­pli­ca­tion to pro­ceed.

The eczema study, BREEZE-AD7, eval­u­at­ed the im­pact of adding baric­i­tinib (ei­ther 2 mg or 4 mg) to stan­dard-of-care top­i­cal cor­ti­cos­teroids in mod­er­ate-se­vere dis­ease pa­tients, ver­sus those who were just giv­en cor­ti­cos­teroids. The ad­di­tion of baric­i­tinib sig­nif­i­cant­ly im­proved dis­ease sever­i­ty — meet­ing the pri­ma­ry end­point of the study at 16 weeks.

Da­ta from the study showed 30.6% (34/111) AD pa­tients treat­ed with 4 mg baric­i­tinib achieved in­ves­ti­ga­tor’s glob­al as­sess­ment for atopic der­mati­tis score of “clear or al­most clear” ver­sus 14.7% (16/109) in place­bo group at Week 16. The study al­so met the sec­ondary end­points mea­sured by Eczema Area and Sever­i­ty In­dex 75 (EASI75) and 4-Point im­prove­ment on the Itch Num­ber Rat­ing Sale (NRS). This is the third pos­i­tive AD tri­al of baric­i­tinib; da­ta from the first two pos­i­tive tri­als were dis­closed in Feb­ru­ary.

“(B)ari will like­ly play a mi­nor role in AD, which may have con­tributed to In­cyte’s pri­or de­ci­sion to no longer co-fund the de­vel­op­ment of the baric­i­tinib pro­gram with LLY, re­sult­ing in roy­al­ties based on glob­al net sales,” SVB Leerink’s An­drew Berens wrote in a note.

Giv­en the dom­i­nance of (Re­gen­eron’s) Dupix­ent in the mod­er­ate and se­vere AD mar­ket and known safe­ty risks of in­fec­tions, ma­lig­nan­cies, and throm­bo­sis with oral JAK in­hibitors, we be­lieve oral, sys­temic JAK in­hibitors may not cap­ture a mean­ing­ful por­tion of the AD mar­ket. While this pro­file rep­re­sents lim­i­ta­tions of the JAK class for sys­temic ther­a­py, we be­lieve this could open the door for a greater role for top­i­cal JAK us­age, which could be pre­scribed in con­junc­tion with non-JAK sys­temic treat­ment.

In­cyte, as part of its quar­ter­ly re­sults in April, in­di­cat­ed it would in­stead fo­cus on shep­herd­ing its in­ter­nal pipeline through clin­i­cal stud­ies, but con­tin­ue to re­ceive roy­al­ties on glob­al net sales of baric­i­tinib, in ac­cor­dance with its deal with Lil­ly. In the first half of 2019, In­cyte earned about $35 mil­lion in baric­i­tinib roy­al­ties.

One of In­cyte’s in­ter­nal as­sets is its ex­per­i­men­tal rux­oli­tinib cream, which is be­ing eval­u­at­ed for use in atopic der­mati­tis and vi­tili­go.

“If top­i­cal rux­oli­tinib can suc­ceed in the two on­go­ing Phase 3 tri­als (da­ta ex­pect­ed in 2020), we be­lieve the drug could be used across the spec­trum of dis­ease and in con­junc­tion with sys­temic, non-JAK ther­a­py. There­fore, while the pro­file of bari and the JAK class sug­gests lim­it­ed sys­temic us­age in AD, it could al­low greater us­age of top­i­cal rux in this dis­ease. We as­sume a 2021 U.S. launch for top­i­cal rux­oli­tinib, with peak rev­enue of ~$1.1bn,” Berens said.

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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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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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.