Al­ny­lam spot­lights just how good the ef­fi­ca­cy da­ta are for givosir­an — tamp­ing down on safe­ty con­cerns

Al­ny­lam $AL­NY took an­oth­er turn on its tran­si­tion lap to a ful­ly fledged com­mer­cial biotech to­day, post­ing its de­tailed — and very promis­ing — ef­fi­ca­cy da­ta for their RNAi drug givosir­an while hop­ing to tamp down the fret­ting over safe­ty is­sues that spoiled their ear­li­er top-line an­nounce­ment.

We knew go­ing in­to the Eu­ro­pean As­so­ci­a­tion for the Study of the Liv­er meet­ing in Vi­en­na that the drug had a great p val­ue — now backed up by a 90% me­di­an re­duc­tion in at­tacks of acute he­pat­ic por­phyr­ia, a painful and de­bil­i­tat­ing ill­ness with no cur­rent­ly ap­proved ther­a­pies. Half of the pa­tients end­ed at­tack free, which would make this a no-brain­er for reg­u­la­tors.

What rat­tled some of the an­a­lysts last time was that the rate of se­ri­ous ad­verse events in the drug arm was more than twice what was seen in the place­bo group. A se­ri­ous safe­ty sig­nal could ham­per or tor­pe­do any drug, and in­deed we learned that sev­er­al of the pa­tients ex­pe­ri­enced se­ri­ous is­sues trig­gered by the ther­a­py. Specif­i­cal­ly, this in­volved cas­es of chron­ic kid­ney dis­ease, pyrex­ia and ab­nor­mal liv­er func­tion test.

Al­ny­lam CEO John Maraganore, though, says that with this drug for this dis­ease in these pa­tients, it will pass muster to soon be­come Al­ny­lam’s sec­ond ap­proved ther­a­py — a land­mark event for a com­pa­ny that has be­come a stan­dard-set­ter for many of the de­vel­op­ment-stage com­pa­nies hop­ing to tran­si­tion in­to mar­ket­ing one day.

Al­ny­lam CEO John Maraganore Get­ty Im­ages

Click on the im­age to see the full-sized ver­sion

“This is a dis­ease that’s about as bad as it gets,” Maraganore told me in a pre­view of to­day’s pre­sen­ta­tion. “It is a ter­ri­ble, ter­ri­ble dis­ease, and ob­vi­ous­ly when you look at the ben­e­fit it’s pret­ty over­whelm­ing.”

Maraganore knows that 2 cas­es of CKD won’t go un­no­ticed by any­one, but in bal­anc­ing the risk/ben­e­fit, he says there’s no doubt that the drug will get a green light. Be­sides, he adds, these pa­tients typ­i­cal­ly have a high risk of kid­ney dis­ease and liv­er is­sues, which reg­u­la­tors will cer­tain­ly take in­to ac­count.

As for pa­tients, he says, the da­ta speak for them­selves, with 93 of 94 pa­tients go­ing on to en­roll in the ex­ten­sion pe­ri­od of the study.

“We couldn’t be more hap­py about the da­ta,” he adds. “If my daugh­ter had this dis­ease I wouldn’t hes­i­tate for a nanosec­ond” to get her on the drug. And then he threw his moth­er and him­self in­to that sce­nario. 

Every­body gets the drug.

That has Jef­feries? Mau­ry Ray­croft fore­cast­ing $600 mil­lion in peak sales by 2030. He adds:

For us, there were no sur­pris­es at EASL, and as a re­sult we are more con­fi­dent in gi­vo’s over­all pro­file and po­ten­tial. The ph.III in­ves­ti­ga­tor and AL­NY be­lieve the drug can be used broad­ly in AHP; add’ly, both AL­NY and the in­ves­ti­ga­tor an­tic­i­pate re­sults will con­tin­ue to im­prove.

Some of the ob­servers ear­li­er al­so weren’t too hap­py about a mixed set of sec­ondary end­points, with the ther­a­py scor­ing for sev­er­al bio­mark­ers of the dis­ease but falling short of sta­tis­ti­cal sig­nif­i­cance on sec­on­daries like pain and fa­tigue and nau­sea, what pa­tients are feel­ing.

Maraganore con­ced­ed those points but coun­tered that you don’t have to hit every sec­ondary to get an ap­proval — true enough — and that a set of pa­tient-re­port­ed out­comes in­di­cat­ed that 89% re­port­ed an im­prove­ment on ther­a­py com­pared to 37% on place­bo.

Maraganore is like­ly right about the caveats. No ther­a­py is per­fect, and reg­u­la­tors will bend over back­wards on side ef­fects if they can get a treat­ment for this dis­ease. That leaves Al­ny­lam com­ing out of EASL with a time­line that an­tic­i­pates an ap­proval by this time next year.

As of now, they’re odds-on fa­vorites for an ap­proval.

Im­age: Kristof­fer Trip­plaar for SIPA AP

John Hood [file photo]

UP­DATE: Cel­gene and the sci­en­tist who cham­pi­oned fe­dra­tinib's rise from Sanofi's R&D grave­yard win FDA OK

Six years after Sanofi gave it up for dead, the FDA has approved the myelofibrosis drug fedratinib, now owned by Celgene.

The drug will be sold as Inrebic, and will soon land in the portfolio at Bristol-Myers Squibb, which is finalizing a deal to acquire Celgene.

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UP­DAT­ED: AveX­is sci­en­tif­ic founder was axed — and No­var­tis names a new CSO in wake of an ethics scan­dal

Now at the center of a storm of controversy over its decision to keep its knowledge of manipulated data hidden from regulators during an FDA review, Novartis CEO Vas Narasimhan has found a longtime veteran in the ranks to head the scientific work underway at AveXis, where the incident occurred. And the scientific founder has hit the exit.

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Ab­b­Vie gets its FDA OK for JAK in­hibitor upadac­i­tinib, but don’t look for this one to hit ex­ecs’ lofty ex­pec­ta­tions

Another big drug approval came through on Friday afternoon as the FDA OK’d AbbVie’s upadacitinib — an oral JAK1 inhibitor that is hitting the rheumatoid arthritis market with a black box warning of serious malignancies, infections and thrombosis reflecting fears associated with the class.

It will be sold as Rinvoq — at a wholesale price of $59,000 a year — and will likely soon face competition from a drug that AbbVie once controlled, and spurned. Reuters reports that a 4-week supply of Humira, by comparison, is $5,174, adding up to about $67,000 a year.

The top 10 fran­chise drugs in bio­phar­ma his­to­ry will earn a to­tal of $1.4T (tril­lion) by 2024 — what does that tell us?

Just in case you were looking for more evidence of just how important Amgen’s patent win on Enbrel is for the company and its investors, EvaluatePharma has come up with a forward-looking consensus estimate on what the list of top 10 drugs will look like in 2024.

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UP­DAT­ED: Sci­en­tist-CEO ac­cused of im­prop­er­ly us­ing con­fi­den­tial in­fo from uni­corn Alec­tor

The executive team at Alector $ALEC has a bone to pick with scientific co-founder Asa Abeliovich. Their latest quarterly rundown has this brief note buried inside:

On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

There’s no explicit word in the filing on what kind of confidential info was involved, but the proceeding got started 2 days ahead of Abeliovich’s IPO.

Abeliovich, formerly a tenured associate professor at Columbia, is a top scientist in the field of neurodegeneration, which is where Alector is targeted. More recently, he’s also helped start up Prevail Therapeutics as the CEO, which raised $125 million in an IPO. And there he’s planning on working on new gene therapies that target genetically defined subpopulations of Parkinson’s disease. Followup programs target Gaucher disease, frontotemporal dementia and synucleinopathies.

But this time Abeliovich is the CEO rather than a founding scientist. And some of their pipeline overlaps with Alector’s.

Abeliovich and Prevail, though, aren’t taking this one lying down.

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Chi­na has be­come a CEO-lev­el pri­or­i­ty for multi­na­tion­al phar­ma­ceu­ti­cal com­pa­nies: the trend and the im­pli­ca­tions

After a “hot” period of rapid growth between 2009 and 2012, and a relatively “cooler” period of slower growth from 2013 to 2015, China has once again become a top-of-mind priority for the CEOs of most large, multinational pharmaceutical companies.

At the International Pharma Forum, hosted in March in Beijing by the R&D Based Pharmaceutical Association Committee (RDPAC) and the Pharmaceutical Research and Manufacturers of America (PhRMA), no fewer than seven CEOs of major multinational pharmaceutical firms participated, including GSK, Eli Lilly, LEO Pharma, Merck KGaA, Pfizer, Sanofi and UCB. A few days earlier, the CEOs of several other large multinationals attended the China Development Forum, an annual business forum hosted by the research arm of China’s State Council. It’s hard to imagine any other country, except the US, having such drawing power at CEO level.

As dis­as­ter struck, Ab­b­Vie’s Rick Gon­za­lez swooped in on Al­ler­gan with an of­fer Brent Saun­ders couldn’t say no to

Early March was a no good, awful, terrible time for Allergan CEO Brent Saunders. His big lead drug had imploded in a Phase III disaster and activists were after his hide — or at least his chairman’s title — as the stock price continued a steady droop that had eviscerated share value for investors.

But it was a perfect time for AbbVie CEO Rick Gonzalez to pick up the phone and ask Saunders if he’d like to consider a “strategic” deal.

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CEO Pascal Soriot via Getty Images

As­traZeneca's jug­ger­naut PARP play­er Lyn­parza scoops up an­oth­er dom­i­nant win in PhI­II as the FDA adds a 'break­through' for Calquence

AstraZeneca’s oncology R&D group under José Baselga keeps churning out hits.

Wednesday morning the pharma giant and their partners at Merck parted the curtains on a successful readout for their Phase III PAOLA-1 study, demonstrating statistically significant improvement in progression-free survival for women with ovarian cancer in a first-line maintenance setting who added their PARP Lynparza to Avastin. This is their second late-stage success in ovarian cancer, which will help stave off rivals like GSK.

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ICER blasts FDA, PTC and Sarep­ta for high prices on DMD drugs Em­flaza, Ex­ondys 51

ICER has some strong words for PTC, Sarepta and the FDA as the US drug price watchdog concludes that as currently priced, their respective new treatments for Duchenne muscular dystrophy are decidedly not cost-effective.

The final report — which cements the conclusions of a draft issued in May — incorporates the opinion of a panel of 17 experts ICER convened in a public meeting last month. It also based its analysis of Emflaza (deflazacort) and Exondys 51 (eteplirsen) on updated annual costs of $81,400 and over $1 million, respectively, after citing “incorrect” lower numbers in the initial calculations.