Sang­amo team rush­es to de­fend first hu­man gene edit­ing da­ta as MPS II ther­a­py of­fers a hit — and a miss

Sang­amo $SG­MO rolled out its first glimpse at the clin­i­cal ef­fi­ca­cy of their gene edit­ing ther­a­py for Hunter syn­drome (MPS II). And while re­searchers were able to point to some clear ev­i­dence that their ap­proach had an im­pact on a key bio­mark­er for the dis­ease for 2 pa­tients, there was a crit­i­cal lack of proof that it was do­ing specif­i­cal­ly what it was de­signed for.

Un­der­stand­ably, Sang­amo con­cen­trat­ed on uri­nary gly­cosamino­gly­cans (GAGs), high­light­ing big drops for both pa­tients in the sec­ond co­hort of the tiny ex­plorato­ry study. 

Ed Con­ner

The gene edit­ing ap­proach they’ve de­vel­oped with zinc fin­ger tech is in­tend­ed to cut in­to the er­rant gene and “in­sert a new copy of the IDS gene in­to a pre­cise lo­ca­tion in the DNA of liv­er cells to en­able a pa­tient’s liv­er to pro­duce a con­tin­u­ous and sta­ble sup­ply of the miss­ing hu­man IDS en­zyme.”

The iduronate-2-sul­fa­tase (IDS) en­zyme is need­ed to break down or re­cy­cle gly­cosamino­gly­cans (GAGs) der­matan sul­fate and he­paran sul­fate. 

The en­zyme gene ther­a­py, if it works, would end the need for reg­u­lar en­zyme re­place­ment in­fu­sions. And the two pa­tients in co­hort two demon­strat­ed mean re­duc­tions in GAG, der­matan sul­fate and he­paran sul­fate of 51%, 32%, and 61%.

That’s good.

How­ev­er, there was al­so this:

At base­line and for the first 16 weeks post-dos­ing of SB-913, plas­ma IDS ac­tiv­i­ty (mea­sure­ments ob­tained at trough of week­ly ERT dos­ing) was be­low the lev­el of quan­tifi­ca­tion of the cur­rent as­say.

That’s what Twit­ter be­gan buzzing about, trig­ger­ing a rapid drop in Sang­amo’s shares.  

Sandy Macrae

In a call with an­a­lysts, Sang­amo ex­ecs rushed to fight back against the back­lash.

That lack of ev­i­dence that the ther­a­py cre­ates the en­zyme need­ed, “doesn’t mean IDS isn’t be­ing pro­duced,” said Sang­amo CMO Ed Con­ner. “Cells of pa­tients with MSP II are starv­ing for IDS.” And “low lev­els may be suf­fi­cient to sup­press GAG.”

Sang­amo CEO Sandy Macrae al­so fierce­ly de­fend­ed the re­sults, say­ing you can’t get that hit on ef­fi­ca­cy un­less the gene edit­ing was tak­ing ef­fect.

In ad­di­tion, they added that the third co­hort in the study is get­ting a much stronger dose that could have a big­ger ef­fect. And ex­ecs added that they need to de­vel­op a bet­ter as­say for their clin­i­cal work to de­tect IDS. 

That wasn’t enough to over­come the first re­ac­tion by in­vestors. Their stock was down 22% in mid-morn­ing trad­ing.

This tri­al is cru­cial for Sang­amo, which is look­ing for clear ev­i­dence that it can beat its ri­vals in the fast-grow­ing field of gene edit­ing. That ri­val­ry, which in­cludes a va­ri­ety of ap­proach­es to edit­ing genes, is just get­ting start­ed.

Charles Nichols, LSU School of Medicine

Could psy­che­delics tack­le the obe­si­ty cri­sis? A long­time re­searcher in the field says his lat­est mouse study sug­gests po­ten­tial

Psychedelics have experienced a renaissance in recent years amid a torrent of preclinical and clinical research suggesting it might provide a path to treat mood disorders conventional remedies have only scraped at. Now a preclinical trial from a young biotech suggests at least one psychedelic compound has effects beyond the mind, and — if you believe the still very, very early hype — could provide the first single remedy for some of the main complications of obesity.

Deborah Dunsire. Lundbeck

UP­DAT­ED: Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time Monday morning the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation of a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month. In a followup call, Dunsire also noted that the company will likely need 200 to 250 reps for this marketing task on both sides of the Atlantic. And analysts were quick to note that the dealmaking at Lundbeck isn’t done, with another $2 billion to $3 billion available for more deals to beef up the pipeline.

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#UK­BIO19: Join GSK’s Hal Bar­ron and a group of top biotech ex­ecs for our 2nd an­nu­al biotech sum­mit in Lon­don

Over the past 10 years I’ve made a point of getting to know the Golden Triangle and the special role the UK biopharma industry plays there in drug development. The concentration of world class research institutes, some of the most accomplished scientists I’ve ever seen at work and a rising tide of global investment cash leaves an impression that there’s much, much more to come as biotech hubs are birthed and nurtured.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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Ac­celeron drops a de­vel­op­ment pro­gram as #2 drug fails to spark func­tion­al ben­e­fits in pa­tients with a rare neu­ro­mus­cu­lar ail­ment

Acceleron is scrapping a muscular dystrophy development program underway for its number 2 drug in the pipeline after pouring over some failed mid-stage secondary data.

Gone is the ACE-083 project in patients with facioscapulohumeral muscular dystrophy. Their drug hit the primary endpoint on building muscle but flopped on key secondaries for functional improvements in patients, which execs felt was vital to the drug’s success.

Scott Gottlieb, AP Images

Scott Got­tlieb has a new board po­si­tion to add to the re­sume — and this one is fo­cused on a fa­vorite sub­ject

Scott Gottlieb has another position to add to his lengthy roster of boards and advisory roles in the wake of his departure from the helm of the FDA.

He’ll be joining the advisory board of FasterCures, a think tank which former junk bond king Michael Milken set up to help drive more drugs to the market, looking to accelerate drug R&D. That’s a subject close to the heart of Gottlieb, who blazed a trail at the FDA focused on hustling up the process. That helped endear him to the industry, making him one of the most popular commissioners in FDA history.

It’s also likely to be a much less controversial post than his board position at Pfizer, which stirred criticism from Democratic presidential candidate Elizabeth Warren.

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Karyopharm lines up $150 mil­lion cash in­jec­tion to back con­tro­ver­sial drug launch

Karyopharm has entered into a royalty agreement worth up to $150 million to back the launch of their multiple myeloma drug — recently approved by the FDA over the objections of a majority of the agency’s outside experts.

The deal with HealthCare Royalty Partners, worth $75 million now and $75 million once certain regulatory and commercial milestones have been reached, will fund the commercialization of Karyopharm’s oral SINE compound Xpovio (selinexor) for patients with multiple myeloma who have already had at least four prior therapies. The money will help Karyopharm as it markets its newly approved drug and pushes through clinical trials testing the drug on refractory multiple myeloma patients with one to three therapies and patients with treatment-resistant diffuse large B-cell lymphoma. It will give Karyopharm a cushion through mid-2021.

Af­ter a run of CT­LA-4 com­bo fail­ures, sci­en­tists spot­light a way to make it work — in se­lect pa­tients

CTLA-4/PD-(L)1 combinations have been one of the El Dorados of oncology, its promise forever behind that next hill but apparently unattainable after a series of pivotal clinical failures. But researchers at New York’s Memorial Sloan Kettering Cancer Center and the Technical University of Munich think they may know how to fix what’s wrong and boost the drive to next-gen cancer combos.

In a preclinical animal research program, researchers found that within a cell, checkpoints rely on a specific molecule — RNA-sensing molecule RIG-I — to work. If that sounds familiar, it’s because it has already been identified as a target for boosting immune responses and was subject to at least one Phase I/II trial. Pfizer in December allied itself with Kineta with $15 million upfront and $505 million in potential milestones to develop RIG-I immunotherapies, and three years ago Merck purchased German upstart Rigontec for $137 million upfront and over $400 million in potential milestones for the same purpose.

Pur­due Phar­ma files for bank­rupt­cy as first step in $10B opi­oid set­tle­ment

It’s settled. Purdue Pharma has filed for bankruptcy as part of a deal that would see the OxyContin maker hand over $10 billion in cash and other contributions to mitigate the opioid crisis — without acknowledging any wrongdoing in the protracted epidemic that’s resulted in hundreds of thousands of deaths.

The announcement came two weeks after news of a proposed settlement surfaced and largely confirm what’s already been reported.