Al­ler­gan, Richter steer past an­oth­er late-stage pile­up with cariprazine

Cariprazine’s hit-and-miss record in late-stage de­vel­op­ment has been ex­tend­ed by a sting­ing set­back. In­ves­ti­ga­tors for Al­ler­gan ($AGN) and its part­ner Gedeon Richter say that the drug flopped in a Phase III de­pres­sion study, but will nev­er­the­less go back in­to an­oth­er piv­otal study in search of more promis­ing re­sults.

Per­sis­tence in late-stage work is the on­ly rea­son this drug is still in the spot­light. Back in ear­ly 2015 I cov­ered their small, suc­cess­ful Phase III tri­al for cariprazine in schiz­o­phre­nia, which was good enough for the de­vel­op­ers to send back to the FDA for a lat­er ap­proval (as Vray­lar), even though they had re­ject­ed the drug in 2013. Richter has dogged­ly main­tained its faith in the drug af­ter once pro­ject­ing peak po­ten­tial sales at a block­buster rate of $2 bil­lion a year, which shrinks to $200 mil­lion in the hands of some an­a­lysts.

As the com­pa­nies not­ed in their state­ment this morn­ing, it’s not un­usu­al for a Phase III de­pres­sion study to fail. Alk­er­mes re­cent­ly ran in­to the same is­sue with its first shot at a Phase III. The com­pa­ny failed and saw $4 bil­lion in mar­ket cap dis­solve, though it too be­lieves that a fol­lowup Phase III can still de­liv­er the goods. The track record on Phase III de­pres­sion stud­ies is lit­tered with fail­ure and just the oc­ca­sion­al suc­cess.

Reg­u­la­tors of­ten re­quire sev­er­al late-stage stud­ies for a de­pres­sion drug, large­ly be­cause the place­bo ef­fect can be so strong in a de­pres­sion study it’s the on­ly way to ad­vance new drugs, which of­ten go on to be­come wild­ly hit-and-miss in a ther­a­peu­tic mar­ket that re­quires plen­ty of ex­per­i­men­ta­tion. In­ves­ti­ga­tors point­ed to an­oth­er study (MD-75) in which they say they got a pos­i­tive read­out for de­pres­sion, but this time around the drug arm failed to sep­a­rate from a place­bo, of­fer­ing no more help than a sug­ar pill.

Richter didn’t lose the same per­cent­age of eq­ui­ty as Alk­er­mes, but its stock was still dam­aged on the news.

David Nichol­son, Chief R&D Of­fi­cer, Al­ler­gan

The com­pa­nies are al­so con­duct­ing two Phase III stud­ies for bipo­lar de­pres­sion. Al­ler­gan wound up with rights to the drug af­ter a se­ries of merg­ers, trac­ing its own­er­ship back to a pact by For­est Lab­o­ra­to­ries.

“We are dis­ap­point­ed with the re­sults of this tri­al. How­ev­er, we be­lieve that our plan to move for­ward with an­oth­er Phase III study in (ma­jor de­pres­sion) cou­pled with our pre­vi­ous pos­i­tive clin­i­cal tri­al would pro­vide the two stud­ies need­ed for sub­mis­sion. This is an im­por­tant next step to fur­ther de­vel­op the cariprazine pro­gram,” said David Nichol­son, chief R&D of­fi­cer at Al­ler­gan.

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.

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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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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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.

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.

FDA ap­proval lets Foamix set its maid­en ac­ne ther­a­py on course for US mar­ket launch

Months ago, Foamix leaned on its biggest shareholders — Perceptive Advisors and OrbiMed — to financially grease its wheels, ahead of the FDA decision date for its acne therapy. On Friday, that approval came in — and the topical formulation of the antibiotic minocycline is set for a January launch.

The therapy, Amzeeq (formerly known as FMX101), was approved to treat inflammatory lesions of non-nodular moderate-to-severe acne vulgaris in patients aged 9 and older.