Prize fight in Paris: Al­ny­lam and Io­n­is slug it out over PhI­II da­ta in prepa­ra­tion for a block­buster show­down

This morn­ing Al­ny­lam $AL­NY rolled out a bat­tery of stel­lar Phase III da­ta on their block­buster con­tender patisir­an, which promis­es to go on to be­come the com­pa­ny’s first ap­proved and mar­ket­ed drug af­ter 15 long years of RNAi dis­cov­ery and de­vel­op­ment work. And as of now, it looks like they’ll be go­ing head-to-head with the an­ti­sense ex­perts at Io­n­is $IONS, the un­der­dogs in what promis­es to be a long run­ning fight for a small group of pa­tients suf­fer­ing from rare cas­es of hered­i­tary AT­TR (hAT­TR) amy­loi­do­sis.

John Maraganore

For Al­ny­lam, the key points in the APOL­LO da­ta un­veiled to­day in Paris fo­cus on an im­pres­sive 34-point mean dif­fer­ence in the mod­i­fied neu­ropa­thy im­pair­ment score (mNIS+7) at 18 months, with a 6-point im­prove­ment for pa­tients which un­der­scores that they got some­what bet­ter over that pe­ri­od. There was al­so a 21.1-point mean im­prove­ment in the qual­i­ty of life score, with a 6.7-point im­prove­ment to show that the pa­tients al­so felt bet­ter.

Just hours ear­li­er, it was Io­n­is that took cen­ter stage, adding to its Phase III da­ta roll­out with a 19.73-point mean change in dis­ease scale at 15 months, and an 8.69-point ben­e­fit at 8 months. Their qual­i­ty of life scores reg­is­tered an 11.68-point mean im­prove­ment, with a 6.4-point ben­e­fit that showed their pa­tients al­so re­spond­ed bet­ter with treat­ment.

“We beat them on both,” Al­ny­lam CEO John Maraganore tells me flat­ly, “with the caveat that these aren’t com­par­a­tive (head-to-head) stud­ies. We clear­ly have a more sub­stan­tial treat­ment ef­fect.”

“This is a big win,” adds the CEO. “It’s a nice way to de­but the ad­vent of this tech­nol­o­gy in med­i­cine.”

The mar­ket agreed with Maraganore. Al­ny­lam shares shot up 13%, with Io­n­is down 8% af­ter the matchup.

Stan­ley Crooke. Im­age: OTS

Maraganore — who’s stuck with RNAi through the good years and the bad as Big Phar­ma dropped out or came in­to the emerg­ing field — hasn’t made his own peak sales pro­jec­tions here, but he al­so isn’t shy of not­ing an­a­lysts’ pro­jec­tions rang­ing up to $2 bil­lion worth of year­ly rev­enue. And he’s al­ready been ramp­ing up com­mer­cial ac­tiv­i­ties in the US and Eu­rope, while their big part­ner Sanofi $SNY takes on the rest of the world.

Io­n­is CEO Stan Crooke has heard the an­a­lysts cheer­ing Al­ny­lam. And he’s not about to roll over and play dead now.

“We think we’ll win in the mar­ket­place,” Crooke told me in the lead-up to to­day’s da­ta re­veal, adding that “there are peo­ple who think oth­er­wise.”

So what does Io­n­is have that Al­ny­lam doesn’t? Crooke — who hadn’t seen the Al­ny­lam re­sults when we talked ahead of Thurs­day’s ses­sions — says there’s lots on the ta­ble.

First, he can point to 8-month and 15-month re­sults which demon­strate sig­nif­i­cant suc­cess ahead the 18-month mark at Al­ny­lam. He’s not talk­ing price yet — no one does at this stage — but “the cost of ther­a­py will be sub­stan­tial­ly bet­ter.” And he’s heard Al­ny­lam hint­ing about Soliris style prices, which could land it on the list of the top 10 most ex­pen­sive ther­a­pies.

“We’ll win be­cause we think in­ot­ersen is easy to use,” he adds, adding point­ed­ly that this isn’t their first time out on the mar­ket. Where the Al­ny­lam ther­a­py has to be in­fused, ex­pos­ing pa­tients to re­ac­tions that can leave them un­able to work, he’ll be sell­ing a treat­ment that can be self-ad­min­is­tered at home.

Io­n­is, though, al­so had to deal with the death of a pa­tient from throm­bo­cy­tope­nia dur­ing its study, throw­ing in an added safe­ty fac­tor that could play to Al­ny­lam’s ad­van­tage — as many an­a­lysts would be will­ing to tell you. Since that case oc­curred, though, the biotech added a more care­ful screen­ing process to pre­vent any new in­ci­dents.

“I think both drugs will be very suc­cess­ful,” Crooke sums up. But any­one who counts Io­n­is out now, he adds, is in for a big sur­prise.

The sales num­bers will pro­vide the score on who’s win­ning.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

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Left to right, top to bottom: Carl Gordon, Adam Stone, Peter Moglia, David Schenkein, Robert Nelsen, Carol Gallagher; Srinivas Akkaraju, Ray Debbane, Jim Flynn, Peter Kolchinsky, Thilo Schroeder, Brad Bolzon

UP­DAT­ED: The top 100 bio­phar­ma ven­ture in­vestors at the mega­bil­lions deal ta­ble

The VC crowd took a step back last year, but nevertheless maintained a furious pace of new investments in therapeutic tech platforms and biotech startups. And the top 100 players completely dominated the megabillions game.

Just looking at the number of deals done by each of the top 100, OrbiMed came in at the top, with 20, followed by Alexandria (18), Perceptive (16) and the ubiquitous RA Capital at 16. It’s impossible to say exactly how much they invested in total — those numbers are only rarely provided — but it is clear from the numbers assembled by Chris Dokomajilar at DealForma who’s most likely to be found sitting at the table during the go-go days of biotech investing.

Dokomajilar tracked $14.06 billion in biotech venture investing last year, a dip from the frenzied pace of $16.02 billion in 2018 and more than $10 billion higher than he recorded for 2010, as the economy was recovering from a profound economic crisis.

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Rahul Ballal, Imara

As sick­le cell pa­tients find new op­tions, NEA-found­ed Imara pitch­es mid-stage al­ter­na­tive for $86M IPO

November 2019 proved to be a fruitful month for patients with blood disorders known as hemoglobinopathies. Within days, the FDA ushered two drugs for sickle cell disease and another for beta thalassemia to the market — livening up a barren field.

Imara, a relatively young plower, is riding on that enthusiasm as it shoots for an $86.25 million IPO.

Imara emerged from New Enterprise Associates’ orphan drug accelerator Cydan in 2016 as a single-product company. $77.3 million in private financing later IMR-687 remains the sole asset in its pipeline; the difference is the drug is now in Phase II for sickle cell disease, with topline data slated for later this year and two other mid-stage beta thalassemia studies lined up.

UP­DAT­ED: RA joins glob­al syn­di­cate to back a $98M round for CAN­bridge

A Beijing-based rare disease and oncology player has raised $98 million to help fund the expansion of its pipeline as well as a commercial portfolio.

CANbridge put out word Tuesday that the global private equity player General Atlantic joined forces with Chinese CRO Wuxi AppTec to lead the Series D, with both ready to chip in an extra $10 million each under the right conditions. The syndicate includes RA Capital Management, Hudson Bay Capital Management, YuanMing Prudence Fund and Tigermed.

Carol Robinson, Professor Dame Carol Robinson Research Group

UP­DAT­ED: Drug dis­cov­ery in HD: Ox­ford spin­of­f's mass spec­trom­e­try ap­proach scores fresh fund­ing

The technology used to detect explosives at airports — mass spectrometry — is being piloted as an engine for drug discovery.

Mass spectrometry is a tool designed to measure with profound accuracy the mass of a single molecule. Typically, mass spectrometers can be used to identify unknown compounds, to quantify known compounds, and to determine the structure and chemical properties of molecules.

Lars Fruergaard Jørgensen, chief executive officer of Novo Nordisk A/S, (via Getty Images)

The list of the 11 block­busters-to-be in line for a 2020 launch high­light agony and ec­sta­sy of drug R&D

For all the talk about unmet medical need and patients first and so on, the key criteria investors watch for any new drug in the pipelines is peak sales projection. Are you going to hit the blockbuster mark, at $1 billion-plus, or are you going to be an also-ran in the sales department?

Of course, analysts’ peak sales projections by themselves are of limited value in many cases. When the PCSK9 drugs started arriving 5 years ago, Repatha was billed as a $2.5 billion peak earner. They’re nowhere near that, with new competition threatening current levels. And if Biogen’s controversial Alzheimer’s drug aducanumab (submission planned but not on the list) is approved, per chance, will payers cover it?

Maybe not. And then those $10 billion in peak sales assumptions would go straight down the drain.

But, analysts are analysts, and peak sales projections have to be factored in when assessing the top experimental drugs up for a launch in the year ahead.

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UP­DAT­ED: Chi­na ap­proves flu drug be­ing tout­ed as a po­ten­tial coro­n­avirus treat­ment amid a rush of clin­i­cal stud­ies

One of the three drugs that China’s Ministry of Science and Technology has tapped as potential COVID-19 treatments to watch has notched its first Chinese OK — for the flu.

While there’s no proof yet that fapilavir, or favipiravir, is the cure that patients and physicians are yearning for, it stands out for a unique constellation of qualities. It’s been commercially available in Japan for several years (unlike Gilead’s experimental remdesivir) yet it’s new to China (unlike the malaria drug chloroquine phosphate). Perhaps more importantly, a domestic biotech — Zhejiang Hisun Pharma — owns the rights to manufacture and market the drug, preempting any concerns about patents.

FDA goes on high alert as coro­n­avirus rais­es threat to drug man­u­fac­tur­ing and clin­i­cal tri­als grind to a halt

The FDA isn’t quite sure just what the coronavirus outbreak in China will mean for the US pharma industry, but it has the potential to trigger a host of troublesome issues around the supply chain the country is directly plugged into.

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