No­var­tis-backed Cona­tus high­lights a sil­ver lin­ing, but PhI­Ib NASH-re­lat­ed set­back caus­es whiplash in share price

The fairy tale sto­ry at Cona­tus Phar­ma­ceu­ti­cals has tak­en a nasty twist.

A lit­tle more than a year af­ter phar­ma gi­ant No­var­tis stepped in with an up­front pay­ment to bag li­cens­ing rights to its liv­er drug that was as big as the biotech’s mar­ket cap, their first Phase IIb tri­al for liv­er dis­ease failed the pri­ma­ry end­point. And their stock price $CNAT im­me­di­ate­ly tanked, plung­ing 34%.

Steven Men­to

There was vir­tu­al­ly no dif­fer­ence be­tween the re­sponse rate in the over­all pop­u­la­tion tak­ing em­ri­c­as­an com­pared to a place­bo. In­ves­ti­ga­tors, though, did find some en­cour­age­ment in sub­group analy­sis, not­ing some bet­ter num­bers for ad­vanced fi­bro­sis and ear­ly cir­rho­sis. But there were al­so sev­er­al miss­es as well.

That’s clear­ly not what the San Diego-based biotech was look­ing for when they start­ed the POLT-HCV-SVR tri­al about 4 years ago. No­var­tis pro­vid­ed a $50 mil­lion up­front, agreed to pay half of the Phase IIb costs for part of the over­all pro­gram and said it would pro­vide an­oth­er $7 mil­lion if it de­cid­ed to ex­er­cise its op­tion in the deal.

Ac­cord­ing to an SEC fil­ing at the time, No­var­tis al­so said it would pro­vide up to $650 mil­lion in mile­stones for the work, which in­cludes two oth­er Phase IIb tri­als. No­var­tis is look­ing for drugs it can com­bine with an in­ter­nal Far­ne­soid X re­cep­tor (FXR) ag­o­nist in clin­i­cal de­vel­op­ment for NASH. The phar­ma gi­ant is al­so on the hook to ex­e­cute Phase III, if it choos­es to move ahead.

Cona­tus CEO Steven Men­to stayed fo­cused on the pos­i­tive:

We are par­tic­u­lar­ly en­cour­aged by the 95% re­sponse rate in a sub­group of ad­vanced fi­bro­sis and ear­ly cir­rho­sis pa­tients with a fa­vor­able two-year safe­ty pro­file. In ad­di­tion, in pa­tients with the po­ten­tial to con­tin­ue wors­en­ing, those less than F6 at base­line, on­ly 2 of 26 (7.7%) on em­ri­c­as­an com­pared with 5 of 17 (29.4%) on place­bo showed an in­crease in fi­bro­sis score at year 2 – a treat­ment dif­fer­ence of 21.7 per­cent­age points. We al­so plan to eval­u­ate re­spons­es in ad­di­tion­al sub­groups in a va­ri­ety of sec­ondary and ex­plorato­ry end­points to learn as much as pos­si­ble from this da­ta-rich tri­al.

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.

Drug com­pa­nies reach $260M set­tle­ment just ahead of opi­oid tri­al; Oys­ter Point set terms for $85M IPO

→ Hours before the first federal opioid trial was set to begin, three drug distributors and an opioid manufacturer agreed to a $260 million agreement settlement, the Wall Street Journal was the first to report. The deal — which will see McKesson, Cardinal Health and AmerisourceBergen pay $215 million to Summit and Cuyahoga counties, and Teva deal out $35 million in cash and addiction treatments — does not resolve the pending, nationwide litigation that may result in a settlement worth upwards of $40 billion. Negotiators in that case, brought by 2,300 tribes, counties and cities nationwide and led by several states’ attorneys general, worked through much of Friday without success. Josh Stein, the attorney general for North Carolina, said they were trying to put together a $48 billion deal.

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrate their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk that uses the same basic ingredient as Genotropin, which the Danish company sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

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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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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.

Sofinno­va-backed Abi­vax touts longer term mid-stage da­ta in ul­cer­a­tive col­i­tis

Two months after Abivax convinced Sofinnova to bankroll several mid-stage studies of its lead drug — ABX464 — with a €12 million stock purchase, the Paris-based biotech has rolled out more data on the anti-inflammatory molecule for all investors to see.

In a Phase IIa maintenance study involving 22 patients with moderate to severe ulcerative colitis who have been failed by previous treatments, 12 achieved clinical remission as assessed by endoscopy. But since only 19 completed the full one-year trial, 16 of whom had an endoscopy, investigators scored the remission rate at 75%. Although there’s no comparator arm, execs were pleased with improvements over an initial two-month, placebo-controlled induction phase by a number of measures ranging from remission to Mayo score and a fecal biomarker.

Alex­ion clinch­es aHUS ap­proval for Ul­tomiris as the clock ticks on Soliris con­ver­sion

Alexion has racked up a second approval for Ultomiris, the successor therapy to Soliris, as its mainstay blockbuster therapy faces a patent review process that could drastically shorten its patent exclusivity.

The FDA OK for atypical hemolytic uremic syndrome (aHUS) on Friday was widely expected after Alexion posted a full slate of positive Phase III data in January. But regulators also flagged concerns about serious meningococcal infections, slapping a black box warning on the label and mandating a REMS.