Two years on, Al­ler­gan’s $1.7B NASH drug still looks weak — at best

Five months af­ter No­var­tis stepped up to col­lab­o­rate with Al­ler­gan on a com­bo NASH pro­gram, Al­ler­gan $AGN has fol­lowed up with what it de­scribes as an en­cour­ag­ing fol­lowup snap­shot to the mid-stage da­ta for their drug ceni­crivi­roc.

But that could take some ex­plain­ing.

Their drug — which flat failed the pri­ma­ry and one sec­ondary in the Phase IIb — un­sur­pris­ing­ly missed the com­pos­ite end­point look­ing at a one-stage drop in pa­tients’ dis­ease score with symp­toms sta­bi­liz­ing.

Af­ter two years of treat­ment, there was no sig­nif­i­cant sep­a­ra­tion be­tween the drug and the place­bo.

Brent Saun­ders Get­ty

In what looks more like a base hit at best, Al­ler­gan says the lat­est up­date from the Phase IIb tri­al al­so shows that 20% of the place­bo pa­tients who crossed over to the drug arm in year 2 hit the com­bined pri­ma­ry end­point with a min­i­mum one-stage drop in their dis­ease score with no wors­en­ing of symp­toms. The place­bo arm rate was 13%.

If you look just at the one-stage drop end­point, the break­out was a more en­cour­ag­ing 35% com­pared to 20%. And re­searchers tout­ed a bet­ter score among pa­tients with high lev­els of fi­bro­sis with plans to pur­sue some ad­di­tion­al analy­sis to see how best to po­si­tion this drug.

These kind of mixed da­ta on this drug is not what Al­ler­gan’s back­ers want to see at this point. But the ex­ec crew says they are ea­ger­ly pur­su­ing the Phase III, re­cruit­ing 2,000 pa­tients with a one-year end­point they be­lieve they can hit. And R&D chief David Nichol­son says any weak­ness in the new Phase IIb up­date was due to miss­ing da­ta and an unan­tic­i­pat­ed place­bo re­sponse — none of which is dulling his en­thu­si­asm for Phase III.

In a state­ment to End­points News, he not­ed:

“The da­ta we have ac­cu­mu­lat­ed con­vinces both Al­ler­gan, as well as our ex­ter­nal ex­perts, that CVC has an­tifi­brot­ic ac­tiv­i­ty in pa­tients suf­fer­ing from NASH. Our phase 2 CEN­TAUR study has twice and in­de­pen­dent­ly shown a re­duc­tion in fi­bro­sis fol­low­ing 1 year of treat­ment. This an­tifi­brot­ic ac­tiv­i­ty is most promi­nent in se­vere­ly ill pa­tients, and un­like place­bo treat­ed pa­tients, it was durable in the ma­jor­i­ty of pa­tients re­ceiv­ing CVC. The stud­ies per­formed to date in­di­cate that CVC can be safe­ly ad­min­is­tered to NASH pa­tients. As it re­lates to the year two da­ta, the re­sults were con­found­ed by miss­ing da­ta, and high­er than ex­pect­ed place­bo rates, name­ly in pa­tients with ear­ly stage dis­ease; this was not unan­tic­i­pat­ed. Larg­er Phase 3 stud­ies are now need­ed, as al­ways, to con­firm the ef­fi­ca­cy and safe­ty pro­file sug­gest­ed by our phase 2 da­ta.”

Al­ler­gan agreed to pay up to $1.7 bil­lion to buy this drug in their ac­qui­si­tion of To­bi­ra last fall, a 6x pre­mi­um that sur­prised quite a few an­a­lysts af­ter the biotech saw its Phase IIb study flop and its share price was crushed. The drug hit one of the sec­on­daries, though, which en­cour­aged Al­ler­gan to step in.

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

Endpoints News

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How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

Endpoints News

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.

John Oyler, Endpoints

BeiGene lines up its first shot at crack­ing the megablock­buster PD-1 mar­ket for lung can­cer. But can they over­come un­der­dog sta­tus?

BeiGene took another big step towards challenging Merck, Bristol-Myers Squibb, AstraZeneca and some other Big Pharma heavyweights for a share of the lucrative lung cancer market for the PD-(L)1s racking up billions in annual revenue.

The China-based biotech $BGNE run by CEO John Oyler posted positive top-line progression-free survival results for their pivotal Chinese study on their PD-1 antibody tislelizumab combined with chemo for squamous non-small cell lung cancer in frontline cases. Squamous NSCLC accounts for about 30% of the overall lung cancer market.

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Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III VOYAGER before they give a judgment.