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.

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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A new chap­ter in the de­cen­tral­ized clin­i­cal tri­al ap­proach

Despite the promised decentralized trial revolution, we haven’t yet moved the needle in a significant way, although we are seeing far bolder commitments to this as we continue to experience the pandemic restrictions for some time to come. The vision of grandeur is one thing, but operationalizing and execution are another and recognising that change, particularly mid-flight on studies, is worthy of thorough evaluation and consideration in order to achieve success. Here we will discuss one of the critical building blocks of a Decentralized and Remote Trial strategy: TeleConsent; more than paper under glass, it is a paradigm change and key digital enabler.

Pur­due Phar­ma signs guilty plea, preps $8B+ set­tle­ment on Oxy con­tro­ver­sy — re­port; Flag­ship brings in a comms chief

Purdue Pharma may soon be signing off on a guilty plea and an $8 million-plus settlement to wrap up its controversial role distributing OxyContin.

The AP has the breaking story this morning.

Purdue filed for bankruptcy last year, along with Insys and followed by Mallinckrodt, as it navigated its way through a blizzard of litigation surrounding Oxy, which triggered an epidemic of abuse around the country.

Pfizer CEO Albert Bourla (Drew Angerer/Getty Images)

Pfiz­er is on the verge of claim­ing a multi­bil­lion-dol­lar first-mover ad­van­tage with their Covid-19 vac­cine — an­a­lyst

From the beginning, Pfizer CEO Albert Bourla eschewed government funding for his Covid-19 vaccine work with BioNTech, willing to take all the $2 billion-plus risk of a lightning-fast development campaign in exchange for all the rewards that could fall its way with success. And now that the pharma giant has seized a solid lead in the race to the market, those rewards loom large.

SVB Leerink’s Geoff Porges has been running the numbers on Pfizer’s vaccine, the mRNA BNT162b2 program that the German biotech partnered on. And he sees a $3.5 billion peak in windfall revenue next year alone. Even after the pandemic is brought to heel, though, Porges sees a continuing blockbuster role for this vaccine as people around the world look to guard against a new, thoroughly endemic virus that will pose a permanent threat.

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UP­DAT­ED: CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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RBC's Bri­an Abra­hams holds a mock ad­comm on Bio­gen's iffy ad­u­canum­ab da­ta — and most of these ex­perts don't see a path to an ap­proval

As catalysts go, few loom larger than the aducanumab adcomm slated for Nov. 6.

With its big franchise under assault, Biogen is betting the ranch that its mixed late-stage Alzheimer’s data can squeak past the experts and regulators and get onto the market. And the topic — after a decade of Alzheimer’s R&D disasters in what still represents the El Dorado of drug markets — remains in the center ring of discussions around late-stage pipeline prospects.

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Un­fazed by PhII miss, Roche ush­ers Prothena's Parkin­son's drug in­to late-stage tri­al — a $60M move

Prothena’s prasinezumab may not have met the primary endpoint in Phase II, but its partners at Roche are seeing enough to move it into a late-stage trial for Parkinson’s disease.

The Phase IIb will build on the Phase II PASADENA study, adding a subgroup of early Parkinson’s patients on stable levodopa therapy to the population.

It’s a significant milestone for a $600 million deal that dates back to 2013, as dosing of the first patient — expected next year — will trigger a $60 million milestone payment to Prothena.

CEO Grace Colón (InCarda)

Look­ing to re­pur­pose an old drug to treat ir­reg­u­lar heart­beats, In­Car­da rais­es $30M in first Se­ries C close

A little less than two years after completing its $42 million Series B round, InCarda has returned to the venture well.

The San Francisco-based biotech announced the first portion of its Series C on Wednesday, pulling in $30 million in new funding. Most of the money will give enough runway for InCarda’s InRhythm program, an inhaled therapeutic aiming to treat sudden episodes of irregular heartbeats, through its Phase II trials and prepare it for Phase III.