Lil­ly shows more pos­i­tive Crohn's da­ta for its IL-23 in­hibitor as it con­tin­ues to chase down ri­vals

About a year and a half af­ter pre­sent­ing pos­i­tive topline re­sults in Crohn’s dis­ease, Eli Lil­ly gave its ex­per­i­men­tal IL-23 an­ti-in­flam­ma­to­ry mirik­izum­ab a boost Mon­day with new da­ta.

The fresh in­fo comes from the Phase II study and is a 52-week fol­low-up of the orig­i­nal tri­al. Mirik­izum­ab showed that, af­ter the ini­tial 12-week pe­ri­od, pa­tients who con­tin­ued treat­ment for an­oth­er 40 weeks saw fur­ther im­prove­ment in en­do­scop­ic re­sponse and Pa­tient-Re­port­ed Out­comes re­mis­sion.

Lo­tus Mall­bris

“We are very ex­cit­ed about this da­ta; this is the first dis­clo­sure of both new ef­fi­ca­cy and safe­ty that shows not on­ly an im­me­di­ate re­sponse, but most im­por­tant­ly, a con­tin­u­ous ef­fi­ca­cy re­sponse,” Lil­ly glob­al im­munol­o­gy chief Lo­tus Mall­bris told End­points News.

Orig­i­nal­ly, the tri­al mea­sured three dif­fer­ent dos­es for en­do­scop­ic re­sponse against a place­bo at week 12. The study met the pri­ma­ry end­point as high­er dos­es pro­gres­sive­ly saw greater re­sponse, with 25.8%, 37.5%, and 43.8% of pa­tients hit­ting the mark com­pared to 10.9 per­cent of place­bo pa­tients.

PRO re­mis­sion was a sec­ondary end­point in that study por­tion, and it was achieved in 12.9%, 28.1% and 21.9% of pa­tients in the three dos­ing arms, com­pared to 6.3% of pa­tients treat­ed with place­bo.

In the fol­low-up pe­ri­od, Eli Lil­ly eval­u­at­ed fur­ther ef­fi­ca­cy and safe­ty as well as two dos­ing meth­ods — in­tra­venous and sub­cu­ta­neous ad­min­is­tra­tion. Af­ter 12 weeks, pa­tients who showed en­do­scop­ic im­prove­ment were ran­dom­ized to con­tin­ue mirik­izum­ab ei­ther through IV or or in­jec­tion. Those who did not show en­do­scop­ic im­prove­ment or who had been orig­i­nal­ly ran­dom­ized to place­bo all re­ceived IV treat­ment cours­es.

At the end of 52 weeks, 58.5% of pa­tients in the IV dos­ing group saw an en­do­scop­ic re­sponse, as well as 58.7% in the oth­er group. Ad­di­tion­al­ly, PRO re­mis­sion was achieved by 46.3% of pa­tients dosed through an IV and 45.6% dosed by in­jec­tion. There was no place­bo group in the fol­low-up pe­ri­od.

“Not on­ly did we con­tin­ue with the pa­tients who were re­spon­ders, the pa­tients that were not re­spond­ing in any dose in­clud­ing place­bo got a sec­ond chance to see if they could re­spond,” Mall­bris said. “And that’s the key here, you give the pa­tients a sec­ond chance to get treat­ment.”

Eli Lil­ly de­fined en­do­scop­ic re­sponse as at least a 50% re­duc­tion in bow­el lin­ing in­flam­ma­tion as seen dur­ing an en­doscopy. Mean­while, PRO re­mis­sion was char­ac­ter­ized as an av­er­age dai­ly stool fre­quen­cy of less than or equal to 2.5 times and ab­dom­i­nal pain less than or equal to 1. Mirik­izum­ab has since moved on­to Phase III in Crohn’s dis­ease af­ter Eli Lil­ly re­port­ed the topline re­sults.

The In­di­anapo­lis-based phar­ma is test­ing the pro­gram in two oth­er in­di­ca­tions as well: pso­ri­a­sis and ul­cer­a­tive col­i­tis. Tri­als for both fields are al­so in Phase III, with mirik­izum­ab show­ing su­pe­ri­or­i­ty to No­var­tis’ IL-17 drug Cosen­tyx for pso­ri­a­sis back in Ju­ly. Phase III da­ta in UC are ex­pect­ed some­time in the first half of 2021, Mall­bris said, with Phase III Crohn’s da­ta still a ways away giv­en that the tri­al just be­gan en­roll­ment.

How­ev­er, Ab­b­Vie may have beat­en Lil­ly to the punch with its IL-23 Skyrizi, which is al­ready ap­proved and demon­strat­ed even bet­ter num­bers com­pared to Cosen­tyx. Eli Lil­ly doesn’t have any cur­rent­ly ap­proved drugs in UC or Crohn’s and every­thing in the field is chas­ing the Ab­b­Vie block­buster Hu­mi­ra, ap­proved for a swath of au­toim­mune con­di­tions. Ab­b­Vie is po­si­tion­ing Skyrizi as a po­ten­tial suc­ces­sor to the TNF block­er, with peak sales es­ti­mat­ed as high as $5 bil­lion by its ex­ec­u­tive team.

Mall­bris said the ul­ti­mate goal for mirik­izum­ab is to be­come the first IL-23 ap­proved for UC as that are­na has seen less de­vel­op­ment than pso­ri­a­sis and Crohn’s.

“There are few­er bi­o­log­ics [in UC]. The ef­fi­ca­cy of those bi­o­log­ics is not re­al­ly sat­is­fac­to­ry,” Mall­bris said.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Top gene ther­a­py deals, M&A pacts in 2020 high­light an­oth­er big year in one of the hottest fields in bio­phar­ma

Chris Dokomajilar at DealForma has been crunching the numbers on gene therapy deals over the last 2 years and came away with a few key observations.

Both the upfront cash and deal totals last year backed off a bit from the record high hit in 2019, but the totals are still running well ahead of anything we’ve seen in the years prior to 2019/2020.
2020 R&D partnerships came in at 23 deals, with $1.1 billion in disclosed upfront cash and equity and more than $8.5 billion in total deal value. Looking at 2019-2020 M&A, Dokomajilar found: 9 Acquisitions, with over $11.1 billion in disclosed upfront cash and equity and more than $13.4 billion in total M&A value.

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Bob Nelsen (Michael Kovac/Getty Images)

ARCH an­nounces largest fund yet, rais­ing $1.85B to back men­tal health, cell and gene edit­ing ap­proach­es

Nearly a year ago, as the pandemic encroached and the stock market cratered, Flagship and ARCH Venture announced three mega-funds worth a combined $2.6 billion. They wanted, ARCH’s Bob Nelsen said, to restore confidence “that there was money out there and a lot of it” to invest in biotech.

Since then, the stock market has returned — almost frighteningly so — and Nelsen has kept raising and spending cash. On Thursday, he announced a new fund, worth $1.85 billion. It’s the largest pot yet for a VC famous for its deep pockets.

Take­da earns win for its TKI in­hibitor in tiny lung can­cer group — but GI side ef­fects could be an ear­ly red flag

Japanese drugmaker Takeda has made a big push in recent years to build a hand in oncology, particularly in the next-gen cancer space. One of those candidates, tyrosine kinase inhibitor (TKI) mobocertinib, recently earned the FDA’s interest in a small section of untreated lung cancer patients, but will severe GI side effects be a roadblock?

Takeda’s oral mobocertinib posted clinically significant objective response rates in a Phase I/II adaptive trial drugging metastatic non-small cell lung cancer patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, according to data presented Thursday at the virtual World Conference on Lung Cancer.

Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Janet Woodcock (AP Images)

Ad­vo­ca­cy groups don't want Janet Wood­cock to head the FDA, blast­ing ‘reg­u­la­to­ry fail­ures’ in opi­oid cri­sis

It turns out the controversies around Janet Woodcock’s regulatory legacy weren’t limited to Sarepta’s eteplirsen.

A coalition of advocacy groups dedicated to the opioid crisis urged Norris Cochran and Xavier Becerra — the acting and designated HHS secretary, respectively — to keep her reign as interim FDA chief a “very short transition.” During her lengthy tenure as CDER, they add, Woodcock presided over “one of the worst regulatory agency failures in U.S. history.”

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Dean Li kicks off Mer­ck­'s post-Roger Perl­mut­ter era by team­ing with Arti­va and its off-the-shelf CAR-NK tech

Even though Dean Li has now officially taken over for Roger Perlmutter as R&D chief, Merck’s appetite for dealmaking continues to be ravenous.

Li struck his first big deal at the helm Thursday morning, hammering out a collaboration with Artiva Biotherapeutics that could earn the biotech nearly $1.9 billion when all is said and done. It’s a quick rise and validation for Artiva, which just last June launched with a $78 million Series A.

Vas Narasimhan (AP Images)

BeiGene's PD-1 scores PhI­II win in esophageal can­cer — a 'key in­di­ca­tion' tapped by No­var­tis in $650M deal

Days after bringing BeiGene’s PD-1 into its portfolio, Novartis is adding a feather to its tislelizumab cap.

BeiGene reported that in the second-line setting, the checkpoint inhibitor extended overall survival for patients with esophageal squamous cell carcinoma, a key indication identified by Novartis. It was the primary endpoint in this Phase III trial.

“This is our fourth positive Phase 3 readout for tislelizumab and the first from our large Phase 3 program in gastrointestinal cancers that also include liver, stomach cancers as well as esophageal cancer,” BeiGene’s CMO in immuno-oncology, Yong Ben, said in a statement.

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