He­mo­phil­ia groups warned of 5 deaths among pa­tients tak­ing Roche’s big new block­buster Hem­li­bra

The He­mo­phil­ia Fed­er­a­tion of Amer­i­ca has put out a state­ment not­ing that Roche alert­ed them of the deaths of 5 pa­tients who were tak­ing their new drug Hem­li­bra, cal­cu­lat­ed to be the biggest sin­gle drug launch of the year. And ac­cord­ing to Roche, the alert fol­lowed the death of two pa­tients ear­li­er this year, which they just learned about.

Ac­cord­ing to the state­ment, Roche’s Genen­tech in­formed them of the deaths Mon­day — adding 4 fa­tal­i­ties to the 1 death al­ready re­port­ed ear­ly last year.

The news trig­gered a 1.4% drop in Roche shares Wednes­day morn­ing.

Ac­cord­ing to the HFA:

Genen­tech has lit­tle in­for­ma­tion that they can present­ly share about the cir­cum­stances sur­round­ing the most re­cent pa­tient deaths; how­ev­er, Genen­tech could con­firm that the pa­tients had re­ceived Hem­li­bra as part of com­pas­sion­ate use and ex­pand­ed pa­tient ac­cess.

In a state­ment to End­points News late Tues­day, a spokesper­son for the com­pa­ny said that one of the pa­tients who died was in an ex­pand­ed ac­cess pro­to­col, three re­ceived it fol­low­ing com­pas­sion­ate use re­quests and one was in the HAVEN I tri­al. She added:

To date, five adults tak­ing Hem­li­bra have passed away. For all, the treat­ing physi­cian or in­ves­ti­ga­tor’s as­sess­ment was that the cause of death was un­re­lat­ed to Hem­li­bra (em­pha­sis pro­vid­ed by Roche). We pro­vid­ed the na­tion­al ad­vo­ca­cy groups with this up­date via phone yes­ter­day.

In a fol­lowup, Roche added a time­line:

  • In 2016, one adult tak­ing Hem­li­bra through a re­quest for com­pas­sion­ate use passed away.
  • In 2017, one adult par­tic­i­pat­ing in the Phase III HAVEN 1 clin­i­cal tri­al passed away and one adult tak­ing Hem­li­bra through a re­quest for com­pas­sion­ate use passed away.
  • In 2018, we just re­cent­ly learned that two adults tak­ing Hem­li­bra passed away. Again, the treat­ing physi­cian’s as­sess­ment for both pa­tients was that the cause of death was un­re­lat­ed to Hem­li­bra.

Roche $RHH­BY has had safe­ty is­sues to deal with be­fore on this drug.

The phar­ma gi­ant re­port­ed 2 cas­es of throm­boem­bol­ic events and 3 in­stances of throm­bot­ic mi­croan­giopa­thy from the Haven I Phase III tri­al. Roche rat­tled its most bull­ish fol­low­ers on this drug with the re­port that a pa­tient died on Feb­ru­ary 22, 2017 from a rec­tal he­m­or­rhage af­ter be­ing treat­ed with emi­cizum­ab and a by­pass­ing agent dur­ing a break­through bleed­ing episode. The in­ci­dents were at­trib­uted to the BPAs, which an­gered Shire and No­vo Nordisk, the two key ri­vals who are feel­ing the biggest im­pact from the ar­rival of Hem­li­bra.

Shire in par­tic­u­lar came out gun­ning against Hem­li­bra, which has a peak sales es­ti­mate of $4 bil­lion. Shire has claimed be­fore that Roche has is­sued “in­ac­cu­rate and mis­lead­ing” state­ments about the se­ri­ous ad­verse events tracked in its Phase III – events which con­spired to keep this would-be block­buster un­der a cloud.

Roche, though, nev­er blinked, bag­ging an ap­proval in the US No­vem­ber 17 for one of its biggest drugs in the pipeline, a key win that was bad­ly need­ed to ac­count for the loss of patent pro­tec­tion on 3 big fran­chise drugs. The EU fol­lowed with an OK Feb­ru­ary 18 and Japan fol­lowed suit March 18.

In the US, the FDA added a boxed warn­ing about safe­ty haz­ards. When the drug was ap­proved last fall, the agency not­ed:

Cas­es of throm­bot­ic mi­croan­giopa­thy and throm­bot­ic events were re­port­ed when on av­er­age a cu­mu­la­tive amount of >100 U/kg/24 hours of ac­ti­vat­ed pro­throm­bin com­plex con­cen­trate (aPCC) was ad­min­is­tered for 24 hours or more to pa­tients re­ceiv­ing emi­cizum­ab-kxwh pro­phy­lax­is. The pre­scrib­ing in­for­ma­tion con­tains a boxed warn­ing to mon­i­tor for throm­bot­ic mi­croan­giopa­thy and throm­bot­ic events when aPCC is ad­min­is­tered. If symp­toms oc­cur, aPCC should be dis­con­tin­ued and emi­cizum­ab-kxwh should be sus­pend­ed.

The HFA added:

Genen­tech has a Med­ical Com­mu­ni­ca­tions line at 1(800)-821-8590 for pa­tients, con­cerned com­mu­ni­ty mem­bers, and health­care providers who seek fur­ther in­for­ma­tion. HFA en­cour­ages you to reach out to Genen­tech and/or to your treat­ing physi­cian if you have ques­tions or con­cerns.

Patrik Jonsson, the president of Lilly Bio-Medicines

Who knew? Der­mi­ra’s board kept watch as its stock price tracked Eli Lil­ly’s se­cret bid­ding on a $1.1B buy­out

In just 8 days, from December 6 to December 14, the stock jumped from $7.88 to $12.70 — just under the initial $13 bid. There was no hard news about the company that would explain a rise like that tracking closely to the bid offer, raising the obvious question of whether insider info has leaked out to traders.

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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).

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.

Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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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.

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Gilead claims Tru­va­da patents in HHS’ com­plaint are in­valid

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.

Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

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Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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