Zol­gens­ma did­n't cause an in­fant death, AveX­is ex­ecs say as they spot­light long-term da­ta

Be­fore the re­cent da­ta ma­nip­u­la­tion scan­dal en­gulfed No­var­tis’ star gene ther­a­py Zol­gens­ma, the death of an in­fant in one of their Phase III tri­als threat­ened to sound safe­ty alarms about the spinal mus­cu­lar at­ro­phy treat­ment. But sci­en­tists at the AveX­is sub­sidiary now say an in­ves­ti­ga­tion has cleared that par­tic­u­lar wor­ry.

Nes­tled in a lengthy pre­sen­ta­tion of up­beat da­ta, the up­date of­fers some much-need­ed val­i­da­tion for Zol­gens­ma as ex­ecs scram­ble to re­build their cred­i­bil­i­ty with both reg­u­la­tors and the gen­er­al pub­lic.

Out of the sev­er­al stud­ies tout­ed at the Eu­ro­pean Pae­di­atric Neu­rol­o­gy So­ci­ety Con­gress, there are a few key take­aways: Some of the ear­li­est pa­tients, as old as 5, are hit­ting de­vel­op­men­tal mile­stones in a long-term fol­low-up study; treat­ing in­fants be­fore they show any symp­toms of SMA has al­lowed them to grow up in a way they oth­er­wise nev­er would have; and there’s more ev­i­dence that the gene ther­a­py pre­vents symp­to­matic pa­tients’ from wors­en­ing.

While the au­top­sy re­port find­ings didn’t fea­ture up top, AveX­is ex­ecs did take the time to ad­dress them in a call with re­porters. Af­ter the British in­fant died in the STRIVE-EU study of a se­vere res­pi­ra­to­ry in­fec­tion fol­lowed by neu­ro­log­i­cal com­pli­ca­tions, the in­ves­ti­ga­tor thought the event might be re­lat­ed to treat­ment.

“We had been con­cerned about the po­ten­tial… that Zol­gens­ma might have been caus­ing brain in­flam­ma­tion,” AveX­is chief ex­ec­u­tive Dave Lennon said, as quot­ed by Reuters. “In this case, the orig­i­nal di­ag­no­sis, and that as­so­ci­a­tion, hasn’t held true.”

Al­though Zol­gens­ma might have been re­spon­si­ble for oth­er known side ef­fects such as el­e­vat­ed en­zymes in the liv­er, low platelets and low blood pres­sure, their in­ves­ti­ga­tion found no ev­i­dence of treat­ment-re­lat­ed brain dam­age. The con­clu­sion: SMA Type 1 was the un­der­ly­ing cause for the in­fec­tion, which in turn de­prived the brain of oxy­gen and trig­gered hy­pox­ic-is­chemic brain dam­age.

Mean­while, the rest of the re­sults demon­strate the “life-chang­ing im­pact Zol­gens­ma can have on chil­dren with SMA Type 1” for fam­i­lies who nev­er ex­pect­ed their chil­dren to crawl, sit or walk, said CMO Ol­ga San­ti­a­go in a state­ment.

START, which start­ed out as a 13-pa­tient safe­ty study, is now track­ing 10 of those pa­tients with a mean age of 4.2 years for whom treat­ment was on av­er­age 3.9 years ago. All are alive and the ma­jor­i­ty (sev­en) is not re­ceiv­ing Spin­raza, Bio­gen’s SMA main­te­nance ther­a­py. Six of them do not re­quire dai­ly res­pi­ra­to­ry sup­port, and at least two are able to stand with as­sis­tance in ad­di­tion to two oth­ers who were re­port­ed to be walk­ing in­de­pen­dent­ly.

Se­ri­ous ad­verse events were re­port­ed, af­fect­ing six out of the 13 orig­i­nal pa­tients, but AveX­is main­tained that noth­ing was new.

In the SPR1NT study, pa­tients were treat­ed much younger — less than 6 weeks — as they tend to be di­ag­nosed at birth. It’s on­ly been a few months since the 23 pa­tients were dosed, but among those with two copies of SMN2, six out of 10 were able to sit with­out sup­port for at least 30 sec­onds — a co-pri­ma­ry end­point. Over­all, of the 22 be­ing eval­u­at­ed, all were alive with­out the help of per­ma­nent ven­ti­la­tion.

The fi­nal da­ta cut won’t be tak­en un­til two years af­ter treat­ment, yet these in­ter­im re­sults show why it’s crit­i­cal to di­ag­nose SMA and in­ter­vene as ear­ly as pos­si­ble, ac­cord­ing to San­ti­a­go.

A sep­a­rate Phase III glob­al tri­al dubbed STR1VE is al­so watch­ing for the 30-sec­ond sit­ting as a co-pri­ma­ry end­point. There, so far, 50% of pa­tients in the US tri­al and 6% in the EU tri­al has hit that goal — some­thing that ba­bies with SMA Type 1 would nev­er be able to do, AveX­is em­pha­sized.

The oth­er co-pri­ma­ry is event-free sur­vival as mea­sured by avoid­ance of death or per­ma­nent ven­ti­la­tion. The tri­al is sched­uled to wrap lat­er this year.

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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