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.”

Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

Genen­tech sub­mits a plan to near­ly dou­ble its South San Fran­cis­co foot­print

The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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David Grainger [file photo]

'Dis­con­nect the bas­tard­s' — one biotech's plan to break can­cer cell­s' uni­fied de­fens­es

Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

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While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

Jason Kelly. Mike Blake/Reuters via Adobe

Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.