Ab­b­Vie shares tank on Ro­va-T flop, sud­den re­treat from ac­cel­er­at­ed ap­proval pitch

Ab­b­Vie’s stock $AB­BV is get­ting ham­mered this morn­ing af­ter its $10 bil­lion Ro­va-T pro­gram post­ed poor mid-stage re­sults for third-line small cell lung can­cer, forc­ing the com­pa­ny to scut­tle any plans to seek an ac­cel­er­at­ed ap­proval for the close­ly-watched drug af­ter talks with skep­ti­cal reg­u­la­tors.

Af­ter fan­ning hopes — amid con­sid­er­able skep­ti­cism in some cir­cles — with its pro­jec­tions of a mega-block­buster fu­ture for Ro­va-T, in­ves­ti­ga­tors out­lined a 16% ob­jec­tive re­sponse rate and me­di­an over­all sur­vival of 5.6 months for the drug.

Shares cratered on the terse re­lease, free falling 13% and wip­ing more than $20 bil­lion off its mar­ket cap, which start­ed the day at $178 bil­lion.

Michael Sev­eri­no

The mag­ni­tude of the ORR for the DLL3-high group was dis­mal, leav­ing the fu­ture of the drug in doubt. And by im­pli­ca­tion, some an­a­lysts are won­der­ing just how bad the da­ta are for the full group, ex­pect­ing the fi­nal read out to be even worse.

I queried Ab­b­Vie about the break­down, and a spokesper­son con­firmed the re­sults were for the sub­group.

The da­ta re­port­ed to­day were in pa­tients ex­press­ing high DLL3 com­pris­ing 74 per­cent of the over­all study pop­u­la­tion in TRIN­I­TY.

By fo­cus­ing on DLL3-ex­press­ing can­cers, the mar­ket was ex­pect­ing an ORR in the 40% range. Chemo com­bos are in the 20% area, an­a­lysts note, and IO com­bos are al­so demon­strat­ing ef­fi­ca­cy. So with an IRC as­sess­ment at 16%, Ab­b­Vie is well be­hind the 8 ball, with the FDA chill­ing talk of an ac­cel­er­at­ed ap­proval de­spite the fact that there are no ap­proved op­tions.

Se­vere ad­verse events were record­ed for throm­bo­cy­tope­nia (11%), pho­to­sen­si­tiv­i­ty re­ac­tion (7%) and pleur­al ef­fu­sion (5%).

Ab­b­Vie paid $5.8 bil­lion in cash for this drug, promis­ing up to $4 bil­lion more in mile­stones to ac­quire the lit­tle-known biotech uni­corn Stem­cen­trx. And with mon­ey like that on the ta­ble, ex­pec­ta­tions were run­ning high, fu­el­ing fore­casts that the phar­ma com­pa­ny could get past the even­tu­al loss of patent pro­tec­tion on Hu­mi­ra in style. Ab­b­Vie it­self pro­ject­ed peak sales at $5 bil­lion a year.

To­day, Ab­b­Vie is feel­ing the lash of dis­ap­point­ed an­a­lysts. Here’s Ge­of­frey Porges:

On­col­o­gy is the key growth busi­ness seg­ment for Ab­b­Vie af­ter the loss of ex­clu­siv­i­ty for Hu­mi­ra in 2023, and to­day’s re­sults and reg­u­la­to­ry de­ci­sion call in­to ques­tion the vi­a­bil­i­ty of the com­pa­ny’s cur­rent sol­id tu­mor strat­e­gy.

Com­bined with Bris­tol-My­ers’ Op­di­vo and Yer­voy, Ab­b­Vie was bet­ting that it had a win­ner in small cell lung can­cer, though its first cut of the ear­ly da­ta last year failed to im­press any­one out­side of the com­pa­ny. The drug drops a cy­to­tox­ic bomb right on DLL3-ex­press­ing can­cer cells com­mon in SCLC.

“We con­tin­ue to be­lieve Ro­va-T has po­ten­tial for pa­tients with small cell lung can­cer and oth­er DLL3-ex­press­ing can­cers,” said Mike Sev­eri­no, ex­ec­u­tive vice pres­i­dent of re­search and de­vel­op­ment and chief sci­en­tif­ic of­fi­cer, Ab­b­Vie. “Al­though the re­sults from the study were not what we hoped for, we look for­ward to re­ceiv­ing da­ta from the on­go­ing Phase 3 stud­ies in the first- and sec­ond-line set­tings and re­main com­mit­ted to de­vel­op­ing Ro­va-T for the treat­ment of pa­tients with small cell lung can­cer.”

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

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Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

For the past three years Frazier Healthcare Partners’ Bhaskar Chaudhuri has been carefully and quietly grooming Arcutis Therapeutics, a new dermatology play he co-founded to deliver topical formulations of well-known drugs. Now that the biotech is poised to enter Phase III, he’s being joined by a marquee syndicate for its $94.5 million Series C.

HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

UP­DAT­ED: Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.

Vas Narasimhan. Getty Images

Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

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CD47 play­er Tril­li­um chops dis­cov­ery ef­forts and 40% of staff; Brii Bio inks deal to bring an­tibi­otics to Chi­na

→ One month into his tenure at Canadian microcap biotech Trillium, Jan Skvarka is bringing out the ax as he sorts out the development plans for its CD47 drugs. The restructuring will see the discovery research unit nixed and the headcount will be reduced by 40% (from 43 to 26), reducing the burn rate from CDN$10 million to CDN$4-7 million per quarter. Meanwhile, the company will seek to partner out its preclinical STING agonist program, which it likely doesn’t have enough resources to tend to.

UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

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Take­da tees up $420M deal for celi­ac an­ti­dote, con­tin­u­ing R&D re­fo­cus

Sometime in the 1st century AD, a patient presented to Arataeus looking like a varicose ghost. He was “emaciated and atrophied, pale, feeble and incapable of performing any of his accustomed works,” the Greek physician wrote, with hollow temples and huge veins running all over his body.

A dysfunctional digestive system, Arataeus concluded – an imbalance he attributed to a “heat” deficiency in a system he and other Greeks regarded as functioning similarly to an oven – and coined a term: coeliac disease, after the Greek word for abdomen.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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