Io­n­is says it gath­ered promis­ing PhI­II da­ta for a top rare dis­ease drug, but se­ri­ous safe­ty ques­tions re­main

Io­n­is Phar­ma­ceu­ti­cals $IONS says that its Phase III study of in­ot­ersen (IO­N­IS-TTR­Rx) hit both pri­ma­ry end­points in pa­tients with rare cas­es of fa­mil­ial amy­loid polyneu­ropa­thy (FAP). But in­ves­ti­ga­tors al­so spelled out just how dan­ger­ous this drug can be, cloud­ing its fu­ture with reg­u­la­tors.

The FDA once put this drug on hold, caus­ing Glax­o­SmithK­line to edge away from their col­lab­o­ra­tion on the drug. But GSK still has an op­tion to grab mar­ket­ing rights on the ther­a­py, as Io­n­is push­es ahead with plans to file for an ap­proval.

The ef­fi­ca­cy da­ta weren’t spelled out in the com­pa­ny’s state­ment. But the safe­ty record was.

Dr. Morie Gertz

Re­searchers said that there were three se­ri­ous cas­es of throm­bo­cy­tope­nia, or low platelet lev­els, that were trig­gered by the drug. One of those pa­tients died from an in­tracra­nial he­m­or­rhage. There were al­so two se­ri­ous re­nal ad­verse events, and two oth­er pa­tients had to stop treat­ment fol­low­ing re­nal ob­ser­va­tions that raised in­ves­ti­ga­tors’ con­cerns.

That seemed to dic­tate the re­sponse among in­vestors as Io­n­is shares slid 10% in pre-mar­ket trad­ing.o140

On the pos­i­tive side, there was clear­ly pos­i­tive ef­fi­ca­cy da­ta on the Neu­ropa­thy Im­pair­ment Score +7 (mNIS+7) and the Nor­folk Qual­i­ty of Life Ques­tion­naire-Di­a­bet­ic Neu­ropa­thy over the 15-month study. That helps ex­plain why 95% of the 80% of pa­tients who com­plet­ed the study went on to con­tin­ue ther­a­py in the ex­ten­sion part of the tri­al.

Leerink’s Paul Mat­teis sized up the good, the bad and the ug­ly thus:

The ef­fi­ca­cy re­sults, which show a ben­e­fit on a dis­ease spe­cif­ic scale (mNIS+7) AND qual­i­ty-of-life, are bet­ter than in­vestor ex­pec­ta­tions as the Street was more cau­tious on the lat­ter mea­sure. How­ev­er, the safe­ty of TTR­rx re­mains a ma­jor ques­tion; IONS not­ed that “a de­tailed re­view of safe­ty da­ta from the study is on­go­ing”, and in the press re­lease, the com­pa­ny re­port­ed cas­es of se­ri­ous throm­bo­cy­tope­nia and a death due to in­tracra­nial he­m­or­rhage.

That could all play out to Al­ny­lam’s ben­e­fit. Its lead late-stage drug patisir­an could prove a safer al­ter­na­tive to Io­n­is’ drug, which is why the Cam­bridge-based biotech’s shares shot up 15% this morn­ing.

When the safe­ty is­sue first came up last year, trig­ger­ing the hold, GSK opt­ed to shelve plans for a Phase III study of TTR amy­loid car­diomy­opa­thy.

Transthyretin — or TTR — amy­loi­do­sis is char­ac­ter­ized by the grad­ual ac­cu­mu­la­tion of amy­loid in tis­sue and or­gans that lead to death.

Io­n­is’ stock was hit last week when an FDA warn­ing let­ter was cir­cu­lat­ed high­light­ing the case of an in­ves­ti­ga­tor in a sep­a­rate study who failed to prop­er­ly test platelet lev­els in pa­tients. Some of the an­a­lysts fol­low­ing the com­pa­ny not­ed that it raised some se­ri­ous is­sues on safe­ty re­lat­ed to its re­al-world use — how could physi­cians be ex­pect­ed to mon­i­tor platelet lev­els ef­fec­tive­ly if re­searchers don’t — and the stock, sub­ject to re­peat­ed short at­tacks, took a hit. That is­sue will like­ly to be close­ly con­sid­ered by reg­u­la­tors and out­side ex­perts dur­ing the drug re­view process.

“Fa­mil­ial amy­loid polyneu­ropa­thy is a dev­as­tat­ing ge­net­ic dis­ease that is painful and rapid­ly pro­gres­sive lead­ing to ear­ly death. The pos­i­tive re­sults from the NEU­RO-TTR study to­day are very en­cour­ag­ing for this un­der­served pa­tient pop­u­la­tion,” said  Dr. Morie Gertz, Di­vi­sion of Hema­tol­ogy, Roland Sei­dler Jr. Pro­fes­sor De­part­ment of Med­i­cine. “I have been treat­ing pa­tients with this dis­abling dis­ease for many years, and I am ex­cit­ed about the promise that in­ot­ersen holds to re­store their lives. I be­lieve in­ot­ersen has the po­ten­tial to trans­form the cur­rent stan­dard of care for pa­tients with TTR amy­loi­do­sis.”

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.