Sol­id Bio is hit by an­oth­er set­back as ini­tial biop­sies spot­light a flop for Duchenne MD

Sol­id Bio­sciences has had an­oth­er set­back.

The biotech an­nounced this morn­ing that its dose-as­cend­ing Phase I/II study of its lead gene ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy flopped, send­ing the com­pa­ny in­to over­drive to hus­tle a high­er dose in­to the clin­ic.

Ilan Gan­ot

The com­pa­ny an­nounced Thurs­day morn­ing that a 3-month biop­sy of a hand­ful of pa­tients “showed low lev­els of mi­crody­s­trophin pro­tein ex­pres­sion.” In 2 of 3 pa­tients, pro­tein ex­pres­sion was un­de­tectable by west­ern blot analy­sis. In the third pa­tient the dy­s­trophin ex­pres­sion hit on­ly 5% by west­ern blot analy­sis, while an­a­lysts and the com­pa­ny were look­ing for 10% or bet­ter.

The com­pa­ny’s shares im­plod­ed, plung­ing 68% by the close. Shares of Sarep­ta, which has the on­ly cus­tom ther­a­py on the mar­ket, jumped about 7% and then slid in­to the red.

Giv­en the safe­ty is­sues that the ther­a­py has al­ready run in­to, Leerink’s Joseph Schwartz ques­tioned the com­pa­ny’s abil­i­ty to pow­er up an ef­fec­tive dose with­out threat­en­ing pa­tients.

Our the­sis that in­vestors should fo­cus not on­ly on the quan­ti­ty of mi­crody­s­trophin ex­pres­sion but al­so on the qual­i­ty of the ex­pressed pro­tein ap­pears to be at sig­nif­i­cant risk based up­on the in­creas­ing­ly un­cer­tain abil­i­ty of SGT-001 (Duchenne mus­cu­lar dy­s­tro­phy/DMD) to be safe­ly dose-es­ca­lat­ed to a lev­el which is suf­fi­cient to achieve com­pet­i­tive mi­crody­s­trophin lev­els. We be­lieve it is pru­dent to wait and see if SLDB can achieve ad­e­quate lev­els of ex­pres­sion in a safe man­ner be­fore con­sid­er­ing whether the mi­crody­s­trophin pro­tein that is ex­pressed by SGT-001 is dif­fer­en­ti­at­ed from that of SRPT and PFE (Bam­boo).

CEO Ilan Gan­ot quick­ly spot­light­ed the com­pa­ny’s cash re­serves, a com­mon strat­e­gy for dis­tressed com­pa­nies.

He not­ed: “This strat­e­gy is fur­ther sup­port­ed by our scal­able man­u­fac­tur­ing process, from which we have suf­fi­cient drug prod­uct avail­able to dose es­ca­late with­out de­lay. We have the fi­nan­cial re­sources to ex­e­cute on our plan and look for­ward to com­mu­ni­cat­ing ad­di­tion­al da­ta lat­er this year.”

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 has en­cour­aged hopes 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.

The com­pa­ny ran in­to ear­ly trou­ble, though.

The very first pa­tient to be treat­ed with SGT-001 ex­pe­ri­enced a se­ri­ous ad­verse event, trig­ger­ing alarm bells af­ter in­ves­ti­ga­tors saw a “de­crease in platelet count fol­lowed by a re­duc­tion in red blood cell count, tran­sient re­nal im­pair­ment and ev­i­dence of com­ple­ment ac­ti­va­tion.” That trig­gered a clin­i­cal hold that last­ed sev­er­al months.

It wasn’t the first brush with trou­ble.

In the lead up to its IPO Gan­ot ne­glect­ed to tell in­vestors about an ini­tial clin­i­cal hold on the pro­gram, post­ing that news just ahead of the list­ing. The biotech was al­so forced to note that gene ther­a­py pi­o­neer James Wil­son from Penn had re­signed from their sci­en­tif­ic ad­vi­so­ry board due to ris­ing safe­ty con­cerns re­lat­ed to high dos­ing us­ing the vec­tor he had de­vel­oped.

Martin Shkreli [via Getty]

Pris­on­er #87850-053 does not get to add drug de­vel­op­er to his list of cred­its

Just days after Retrophin shed its last ties to founder Martin Shkreli, the biotech is reporting that the lead drug he co-invented flopped in a pivotal trial. Fosmetpantotenate flunked both the primary and key secondary endpoints in a placebo-controlled trial for a rare disease called pantothenate kinase-associated neurodegeneration, or PKAN.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

Hal Barron. GSK

GSK's Hal Bar­ron her­alds their sec­ond pos­i­tive PhI­II for cru­cial an­ti-BC­MA ther­a­py, point­ing to a push for quick OKs in a crowd­ed field

Hal Barron has his second positive round of Phase III data in hand for his anti-BCMA antibody drug conjugate belantamab mafodotin (GSK2857916). And GSK’s research chief says the data paves the way for their drive in search of an FDA approval for treating multiple myeloma. 

It’s hard to overestimate the importance of this drug for GSK, a cornerstone of Barron’s campaign to make a dramatic impact on the oncology market and provide some long-lost excitement for the pharma giant’s pipeline. They’re putting this BCMA program at the front of that charge — looking to lead a host of rivals all aimed at the same target.

UP­DAT­ED: An em­bold­ened As­traZeneca splurges $95M on a pri­or­i­ty re­view vouch­er. Where do they need the FDA to hus­tle up?

AstraZeneca is in a hurry.

We learned this morning that the pharma giant — not known as a big spender, until recently — forked over $95 million to get its hands on a priority review voucher from Sobi, otherwise known as Swedish Orphan Biovitrum.

That marks another step down on price for a PRV, which allows the holder to slash 4 months off of any FDA review time.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology
ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development
CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

Bob Smith, Pfizer

Pfiz­er is mak­ing a $500M state­ment to­day: Here’s how you be­come a lead play­er in the boom­ing gene ther­a­py sec­tor

Three years ago, Pfizer anted up $150 million in cash to buy Bamboo Therapeutics in Chapel Hill, NC as it cautiously stuck a toe in the small gene therapy pool of research and development.

Company execs followed up a year later with a $100 million expansion of the manufacturing operations they picked up in that deal for the UNC spinout, which came with $495 million in milestones.

And now they’re really going for it.

Endpoints News

Basic subscription required

Unlock this story instantly and join 58,000+ biopharma pros reading Endpoints daily — and it's free.

Video: Putting the AI in R&D — with Badhri Srini­vasan, Tony Wood, Rosana Kapeller, Hugo Ceule­mans, Saurabh Sa­ha and Shoibal Dat­ta

During BIO this year, I had a chance to moderate a panel among some of the top tech experts in biopharma on their real-world use of artificial intelligence in R&D. There’s been a lot said about the potential of AI, but I wanted to explore more about what some of the larger players are actually doing with this technology today, and how they see it advancing in the future. It was a fascinating exchange, which you can see here. The transcript has been edited for brevity and clarity. — John Carroll

Am­gen, Al­ler­gan biosim­i­lar of Roche's block­buster Rit­ux­an clears an­oth­er US piv­otal study 

Novartis $NVS may have given up, but Amgen $AMGN and Allergan $AGN are plowing ahead with their knockoff of Roche’s blockbuster biologic Rituxan in the United States.

Their copycat, ABP 798, was found to have a clinically equivalent impact as Rituxan — meeting the main goal of the study involving CD20-positive B-cell non-Hodgkin’s lymphoma patients. This is the second trial supporting the profile of the biosimilar. In January, it came through with positive PK results in patients with rheumatoid arthritis.

Trump ad­min­is­tra­tion re­vives bid to get drug list prices on TV ads

The Trump administration is not giving up just yet. On Wednesday, the HHS filed an appeal against a judge’s decision in July to overturn a ruling obligating drug manufacturers to disclose the list price of their therapies in television adverts — hours before it was stipulated to go into effect.

In May, the HHS published a final ruling requiring drugmakers to divulge the wholesale acquisition cost— of a 30-day supply of the drug — in tv ads in a bid to enhance price transparency in the United States. The pharmaceutical industry has vehemently opposed the rule, asserting that list prices are not what a typical patient in the United States pays for treatment — that number is typically determined by the type of (or lack thereof) insurance coverage, deductibles and out-of-pocket costs. Although there is truth to that claim, the move was considered symbolic in the Trump administration’s healthcare agenda to hold drugmakers accountable in a climate where skyrocketing drug prices have incensed Americans on both sides of the aisle.