FDA slaps a hold on Sol­id Bio's gene ther­a­py for Duchenne MD in wake of safe­ty alert

Just a few weeks af­ter Sol­id Bio­sciences $SLDB put out an 11th hour no­tice that its gene ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy had been put on a par­tial clin­i­cal hold due to safe­ty con­cerns, just ahead of its $125 mil­lion IPO, the biotech is back Wednes­day evening with the news that the agency has now halt­ed the study in the wake of an ad­verse re­ac­tion to the ther­a­py by the first pa­tient in the tri­al.

The stock plunged 54% af­ter the news hit, sig­ni­fy­ing that this time around in­vestors aren’t quite so san­guine about safe­ty is­sues. But the pain didn’t end there. JP­Mor­gan, which helped on the IPO, turned bear­ish on the news and cau­tioned on the com­pa­ny’s prospects in the wake of a safe­ty is­sue that raised se­ri­ous doubts about Sol­id’s ex­ec­u­tive team. By mid-af­ter­noon on Thurs­day, the stock was down 63%, shear­ing off more than $600 mil­lion in val­ue.

“In our view, it will like­ly take com­pelling clin­i­cal da­ta to re­gain con­fi­dence in man­age­ment (not ex­pect­ed in the near-term),” said JP Mor­gan’s Anu­pam Ra­ma, ac­cord­ing to a Bloomberg re­port.  Ra­ma set the new price at $9, a sick­en­ing drop from the $16 price they launched at.

Sol­id Bio CEO Ilan Gan­ot

This is from Sol­id’s state­ment:

The first pa­tient dosed in the clin­i­cal tri­al was a non-am­bu­la­to­ry ado­les­cent who re­ceived 5E13 vg/kg of SGT-001 on Feb­ru­ary 14, 2018. Sev­er­al days af­ter ad­min­is­tra­tion the pa­tient was hos­pi­tal­ized due to lab­o­ra­to­ry find­ings that in­clud­ed a de­crease in platelet count fol­lowed by a re­duc­tion in red blood cell count and ev­i­dence of com­ple­ment ac­ti­va­tion. The pa­tient showed no signs or symp­toms of co­ag­u­lopa­thy (bleed­ing dis­or­der) and no rel­e­vant changes from base­line in liv­er func­tion tests. The pa­tient re­spond­ed well to med­ical treat­ment and is cur­rent­ly asymp­to­matic. All lab­o­ra­to­ry pa­ra­me­ters have ei­ther im­proved or re­turned to nor­mal, and he is con­tin­u­ing out­pa­tient as­sess­ments per pro­to­col.

The FDA is like­ly on high alert on Sol­id af­ter James Wil­son, a pi­o­neer in gene ther­a­py who de­vel­oped the AAV de­liv­ery tech that Sol­id is us­ing, re­signed from the ad­vi­so­ry board af­ter an an­i­mal study raised a red flag about po­ten­tial safe­ty is­sues when used at a high dose. Wil­son was alarmed af­ter a mon­key was killed by liv­er tox­i­c­i­ty af­ter be­ing ex­posed to a high dose AAV treat­ment, with ev­i­dence of mo­tor neu­ron dam­age in piglets. A num­ber of com­pa­nies use AAV tech in-li­censed for their work. But none of the oth­ers has been hit with a hold.

Sol­id CEO Ilan Gan­ot — a for­mer JP Mor­gan in­vest­ment banker — has made much of the fact that he’s a Duchenne MD dad out to find a gene ther­a­py that could cure the lethal, rare dis­ease. By in­tro­duc­ing a syn­thet­ic dy­s­trophin trans­gene con­struct, called mi­crody­s­trophin, via a vi­ral vec­tor, the com­pa­ny hopes to prove it can do what Sarep­ta and oth­ers have been grop­ing for with one de­ci­sive in­ter­ven­tion. And he had at­tract­ed some heavy­weight back­ers, in­clud­ing RA Cap­i­tal and their col­leagues at Bain.

Some an­a­lysts sup­port­ing Sarep­ta $SRPT in the race to de­vel­op a gene ther­a­py for DMD are like­ly to glee­ful­ly sug­gest that Sol­id’s trou­bles are Sarep­ta’s boon. Sarep­ta has dosed a cou­ple of pa­tients now, look­ing for a one-time ther­a­py to help save boys from a dev­as­tat­ing ill­ness.

Gan­ot’s de­ci­sion to keep the par­tial hold out of the news while it was do­ing a road show on the IPO rais­es ques­tions about the lev­el of trans­paren­cy – or lack it – that al­lows pri­vate drug de­vel­op­ers to op­er­ate in se­cre­cy. Aside from no­ti­fy­ing re­searchers, reg­u­la­tors and pa­tients, a pri­vate de­vel­op­er is not re­quired to air safe­ty is­sues. The FDA cer­tain­ly won’t say any­thing. And we saw the ex­act same thing play out re­cent­ly when Unum filed their IPO, re­veal­ing two pa­tient deaths months ear­li­er and a clin­i­cal hold on the high dose of their lead cell ther­a­py, which they sub­se­quent­ly dumped.

The Cam­bridge, MA-based biotech says it’s work­ing with the FDA on get­ting the hold lift­ed.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Shpigelmacher, a robotics geek and entrepeneur who had drifted into consulting for pharma, wanted to build the real-life equivalent of technology from the 1960s film Fantastic Voyage, the one where a submarine crew is shrunk to “about the size of a microbe” and sent on a mission to repair a scientist’s brain. He scanned the literature, found the lab that was working on the most advanced project — at the Max Planck Institute in Germany, it turned out — and started funding them with money from his own account, along with some seed cash from friends and family.

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The company has sold off its 7.7% stake in Moderna and turned it into $1.2 billion in cash, according to the Times, beefing up the reserves just as Pascal Soriot is wrapping up his $39 billion acquisition of Alexion and its rare disease pipeline.

AstraZeneca’s stock sale follows a similar move by Merck in December. But like its pharma brethren, the British giant is keeping its R&D collaborations with Moderna.

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Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.

In­tro­duc­ing End­pointsF­DA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.