AveX­is of­fers com­pelling rea­sons for a fast FDA OK for gene ther­a­py to treat spinal mus­cu­lar at­ro­phy in in­fants

For most in­fants suf­fer­ing from spinal mus­cu­lar at­ro­phy type 1, the chances are quite high that they could die or re­quire con­stant res­pi­ra­to­ry as­sis­tance ear­ly on to al­low them to keep breath­ing, with no mo­tor func­tion abil­i­ty for sim­ple things like sit­ting unas­sist­ed. Most die be­fore the age of 4.

But in a small Phase I study of 15 pa­tients treat­ed with AveX­is’ $AVXS gene ther­a­py for SMA, all of the pa­tients were able to reach 20 months with­out the need for con­stant res­pi­ra­to­ry sup­port, or dy­ing. And many achieved im­prove­ments in mo­tor symp­toms, speak­ing to the po­ten­tial — though still un­proven — of this as a once-and-done ther­a­py for a rare but dire ail­ment.

The New Eng­land Jour­nal of Med­i­cine pub­lished those com­plete Phase I da­ta points, out to­day, as the biotech pur­sues a piv­otal study while ex­plor­ing the pos­si­bil­i­ty of an ac­cel­er­at­ed FDA ap­proval that could — pos­si­bly — pro­vide a short­cut to com­mer­cial work.

Sean Nolan

The news to­day is re­mark­able for sev­er­al rea­sons. It puts AveX­is in the front ranks of gene ther­a­py com­pa­nies as Spark ap­pears poised to gain a pi­o­neer­ing US ap­proval for its lead gene ther­a­py for an eye dis­ease. And it al­so pos­es a di­rect threat to Bio­gen’s new fran­chise for Spin­raza, priced at $750,000 for the first year — one of the top 10 most ex­pen­sive ther­a­pies in the world — and half that rate for each year af­ter.

“We do have a meet­ing sched­uled late in the fourth quar­ter to meet with the FDA,” says Chica­go-based AveX­is CEO Sean Nolan. “We’ve said we would do every­thing we could to move along the fil­ing and hope­ful­ly the ap­proval. We do see there are a cou­ple of po­ten­tial sce­nar­ios that could lead to a more ac­cel­er­at­ed ap­proval.”

AveX­is an­nounced a month ago that it was launch­ing its piv­otal study of the ther­a­py.

SMA is trig­gered by a ge­net­ic de­fect that de­rails a pro­tein need­ed for mo­tor neu­rons. AveX­is’ ther­a­py is de­signed to pen­e­trate the blood brain bar­ri­er and in­tro­duce cor­rect­ed copies of that gene to fix the prob­lem in SMA1, an in­fan­tile form of the dis­ease that be­comes ap­par­ent in the first 6 months, mak­ing it a par­tic­u­lar­ly good tar­get for gene ther­a­py work.

Bri­an Kas­par

“These kids al­ways go down,” says AveX­is CSO Bri­an Kas­par, who took a leave from his post at the gene ther­a­py cen­ter at Na­tion­wide Chil­dren’s Hos­pi­tal in Colum­bus to spear­head the clin­i­cal work. “They nev­er gain mile­stones, no mo­tor func­tion mile­stones. They won’t sit unas­sist­ed; they’ll nev­er achieve the abil­i­ty to roll over or stand and walk.”

Giv­en its tar­get, and the less­er ef­fect that Spin­raza has demon­strat­ed in the clin­ic, reg­u­la­tors are like­ly to feel con­sid­er­able pres­sure to open the door ear­ly on this ther­a­py, par­tic­u­lar­ly giv­en the pre­ferred treat­ment that Sarep­ta gained for Ex­ondys51 with­out any ac­tu­al da­ta the it helped boys suf­fer­ing from Duchenne MD.

New FDA com­mis­sion­er Scott Got­tlieb has vowed to do what’s nec­es­sary to make cut­ting edge ther­a­pies avail­able as soon as they’ve cleared a bar on ef­fi­ca­cy and safe­ty. And he now has a test case for just where that line has been drawn.

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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