Roche's Xofluza may give rise to re­sis­tant strains, rais­ing fears of a 'worst case sce­nar­i­o'

In 2018, Sh­iono­gi rolled out Xofluza in Japan as a one-dose kill for in­fluen­za, with Roche fol­low­ing suit in the US. Soon, though, Japan­ese reg­u­la­tors no­ticed the drug was lead­ing to re­sis­tant flu strains, and now a new study in Na­ture con­firms the drug leads to spe­cif­ic mu­ta­tions that may ham­per its promise to neu­tral­ize the virus in a sin­gle dose.

An­drew Pekosz John Hop­kins

“In a worst case sce­nario, these mu­ta­tions could ren­der the drug en­tire­ly use­less,” An­drew Pekosz, a mol­e­c­u­lar bi­ol­o­gist at Johns Hop­kins who was not in­volved in the study, told End­points News. “They haven’t yet, and it’s not clear why that’s been the case.”

No­tably, Pekosz said, the mu­tant virus­es have not spread ex­ten­sive­ly in hu­mans. Rather, re­searchers at the Uni­ver­si­ty of Wis­con­sin and the Uni­ver­si­ty of Tokyo took strains from pa­tients in Japan who had re­ceived Xofluza and found some con­tained mu­ta­tions to a struc­ture the virus us­es to repli­cate it­self, called the poly­merase com­plex.

Xofluza, or balox­avir acid, tar­gets this com­plex to kill the virus. When re­searchers test­ed the mu­tant strains in an­i­mal and cell lines, they found it was re­sis­tant to the drug and ca­pa­ble of spread­ing. Of 77 sam­pled chil­dren, 18 (23%) had mu­tant strains.

“This is not the first study, maybe one of the most ex­ten­sive ones, that show a sin­gle mu­ta­tion can cause re­sis­tance,” Pekosz said. “And those re­sis­tant virus­es still seem to have the abil­i­ty to repli­cate and spread just like the wild virus.”

Roche billed Xofluza as the first flu treat­ment ap­proved in 20 years and tout­ed the com­pli­ance ad­van­tages over its pre­de­ces­sor Tam­i­flu; One dose on one day as op­posed to 10 dos­es over 5 days. But re­sis­tance has been a con­tin­u­al prob­lem with such drugs. Most no­tably, the once-com­mon flu drug aman­ta­dine is no longer pre­scribed as vir­tu­al­ly all strains have be­come re­sis­tant.

As Xofluza neared ap­proval, re­searchers warned it may cause re­sis­tance. A New Eng­land Jour­nal of Med­i­cine ed­i­to­r­i­al pub­lished a month be­fore the drug’s US ap­proval found treat­ment led to “the emer­gence of vi­ral es­cape mu­tants with re­duced sus­cep­ti­bil­i­ty.”

“The is­sue for pub­lic health is whether these in­fluen­za virus­es with re­duced sus­cep­ti­bil­i­ty to balox­avir are trans­mis­si­ble,” wrote Tim­o­thy M. Uye­ki.

That ques­tion re­mains in­con­clu­sive, al­though the au­thors of the Na­ture study not­ed that one child who had not re­ceived Xofluza nev­er­the­less test­ed pos­i­tive for a re­sis­tant strain, “sug­gest­ing the pos­si­bil­i­ty of per­son-to-per­son trans­mis­sion of the vari­ant.”

For Pekosz, the ques­tions un­der­score the need for flu drug cock­tails that at­tack the virus from mul­ti­ple an­gles, like how doc­tors treat the HIV; If a virus needs two pre­cise mu­ta­tions to sur­vive and evolve, it’s much more less like­ly to.

“We’re mak­ing it too easy for the virus to es­cape,” he said.

Jude Samulski, Marianne De Backer

Bay­er buys a biotech ‘race horse’ with a $4B deal — $2B in cash — aimed at go­ing big in­to gene ther­a­py

In the latest sign that Big Pharma wants a leading place in the push to develop a new generation of cell and gene therapies, Bayer is stepping up today with a $2 billion cash deal to buy out one of the fast-moving pioneers in the field, while adding up to $2 billion more in milestones if the new pharma subsidiary can deliver the goods.

As part of a continuing series of deals engineered by Bayer BD chief Marianne De Backer, the pharma player has snapped up Asklepios, more commonly referred to in more casual fashion as AskBio. And they are paying top dollar for a Research Triangle Park-based company that raised $225 million a little more than a year ago to back the brainchild of Jude Samulski, the gene therapy pioneer out of the University of North Carolina Gene Therapy Center.

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Patrick Soon-Shiong at the JP Morgan Healthcare Conference, Jan. 13, 2020 (David Paul Morris/Bloomberg via Getty Images)

Af­ter falling be­hind the lead­ers, dissed by some ex­perts, biotech show­man Patrick Soon-Sh­iong fi­nal­ly gets his Covid-19 vac­cine ready for a tri­al. But can it live up to the hype?

In January, when dozens of scientists rushed to start making a vaccine for the then-novel coronavirus, they were joined by an unlikely compatriot: Patrick Soon-Shiong, the billionaire doctor most famous for making big, controversial promises on cancer research.

Soon-Shiong had spent the last 4 years on his “Cancer Moonshot,” but part of his project meant buying a small Seattle biotech that specialized in making common-cold vectors, called adenoviruses, to train the immune system. The billionaire had been using those vectors for oncology, but the company had also developed vaccine candidates for H1N1, Lassa fever and other viruses. When the outbreak began, he pivoted.

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Christian Rommel (via Roche)

Bay­er fol­lows R&D deal spree by raid­ing Roche's can­cer group for its new re­search chief

The day after Bayer signed off on a $4 billion deal designed to put the company among the leaders in gene therapy development, the pharma giant has recruited a new chief for its R&D division. And they opted for an expert in the cancer field.

Christian Rommel, Roche’s head of discovery and early-stage oncology development, has been tapped to take over the job. Joerg Moeller, who got the top research post after early and late-stage development roles were combined 2 years ago, is hitting the exit “to pursue other career opportunities.”

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Albert Bourla, AP

UP­DAT­ED: Where's the Pfiz­er ef­fi­ca­cy read­out? CEO Bourla says 'soon,' but you're go­ing to have to wait for it

Pfizer CEO Albert Bourla had promised repeatedly that the pharma giant would know if its leading Covid-19 vaccine is effective by the end of this month — now just a few days away.

Instead, the company reported early Tuesday that it has yet to conduct any interim efficacy analyses. And it won’t now until sometime next month.

The news was included in a slide for their Q3 report.

In the morning Q3 call with analysts, Bourla says that they expect efficacy data “soon,” but noted that they wouldn’t be able to say anything until all the administrative work was done on the interim, which would take about a week. And he added that Pfizer isn’t going to say anything else about that hot topic until they have the data in hand.

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Charles Baum, Mirati CEO

UP­DAT­ED: Mi­rati plots a march to the FDA for its KRAS G12C drug, breath­ing down Am­gen’s neck with bet­ter da­ta

Mirati Therapeutics $MRTX took another closely-watched step toward a now clearly defined goal to file for an approval for its KRAS G12C cancer drug adagrasib (MRTX849), scoring a higher response rate than the last readout from the class-leading rival at Amgen but still leaving open a raft of important questions about its future.

Following a snapshot of the first handful of responses, where the drug scored a tumor response in 3 of 5 patients with non-small cell lung cancer, the response rate has now slid to 45% among a pooled group of 51 early-stage and Phase II patients, 43% — 6 of 14 — when looking solely at the Phase I/Ib. Those 14 patients had a median treatment duration of 8.2 months, with half still on therapy and 5 of 6 responders still in response.

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Yung Chyung, Scholar Rock CMO (Business Wire)

A dark horse en­trant in­to the spinal mus­cu­lar at­ro­phy field dou­bles its val­ue on some PhII da­ta

The last four years have seen a sudden explosion in treatments for spinal muscular atrophy, a neurodegenerative condition that once led patients — often young ones — with a grim prognosis and no options. The prognosis still isn’t rosy, but now there are three FDA-approved options, enough to make the choice of one difficult.

Now a fourth potential option has entered the mix. Today, Scholar Rock announced the results from a proof-of-concept testing their SMA drug by itself and in combination with Ionis’ Spinraza, showing that all patient cohorts improved on standard scales used for measuring motor function in people with SMA.

Three years in­to a PhI­II pro­gram for a failed Duchenne MD drug, Cataba­sis hauls down the flag and ad­mits de­feat

Three years ago, Catabasis CEO Jill Milne and the crew insisted they had found good reason for great cheer once they plumbed the data from their failed study for the Duchenne MD drug edasalonexent. Plunging into the extended open-label data, they said, you could find solid evidence of efficacy. And that justified a try in Phase III.

But they were wrong.

Monday, after the bell, the little biotech acknowledged that their pivotal attempt following the mid-stage flop was another failure. The primary, change in baseline on the North Star Ambulatory Assessment, and the secondary on timed function tests both came up short of statistical significance.

Ul­tragenyx slams the brakes on rare dis­ease study af­ter all 5 pa­tients are hit with a se­ri­ous set­back

Ultragenyx $RARE and its partners at GeneTx have been forced to halt early-stage study for a drug to treat rare cases of Angelman syndrome after all 5 of the patients being treated for the first time experienced a severe adverse event at the highest dose.

The patients in the study experienced “lower extremity weakness believed to be related to local inflammation due to GTX-102,” triggering a red light on dosing and enrollment.

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Gary Glick, Keith Flaherty

What can a biotech en­tre­pre­neur and a top sci­en­tist come up with on a cou­ple of shared flights? Well...

Just weeks before the pandemic hit the states, Gary Glick and Keith Flaherty had a chance to spend 12 hours together, talking craft and trade on board shared flights as they headed to and from a board meeting together.

It may have been the most fruitful 12 hours of Glick’s productive life. They certainly found plenty to talk about.

Glick, a well known biotech entrepreneur and inflammatory specialist, had bumped up to executive chair at IFM Therapeutics just weeks before, after running through a slate of sizable deals with some major pharma players like Novartis.