Spark takes a beat­ing as he­mo­phil­ia safe­ty set­backs tor­pe­do stock, bur­nish ri­val Bio­Marin

Every tiny gene ther­a­py study run by a pub­lic biotech look­ing to make a break­through in cur­ing a dis­ease has two crit­i­cal fea­tures. There’s the reg­u­la­to­ry side, where FDA and EMA in­sid­ers need to be per­suad­ed of their po­ten­tial. And there’s the mar­ket side, where a host of an­a­lysts — re­al and self-ap­point­ed so­cial me­dia mavens — are ready to jump on any ad­verse event as a sign of im­pend­ing de­feat.

Spark $ONCE CEO Jeff Mar­raz­zo has seen both sides up close. And his stock price is get­ting ham­mered this morn­ing as the mar­ket ze­roes in on a new up­date on the com­pa­ny’s he­mo­phil­ia A pro­gram this morn­ing over­shad­owed by a se­ri­ous ad­verse event and oth­er set­backs that the an­a­lysts quick­ly pounced on — over­shad­ow­ing the more pos­i­tive da­ta the CEO would pre­fer to fo­cus on.

Now that 12 he­mo­phil­ia A pa­tients have been dosed in their Phase I/II study, Mar­raz­zo says that they’ve been able to track a dose-de­pen­dent re­sponse that per­suad­ed them to move ahead in­to a piv­otal Phase III at the high end: 2×10(12) vg/kg.

“We be­lieve that the to­tal­i­ty of the da­ta sup­ports mov­ing in­to Phase III,” Mar­raz­zo, a very care­ful speak­er, tells me.

Re­searchers have ob­served promis­ing re­spons­es for the first 2 pa­tients in the study for more than a year now; step back, says Mar­raz­zo, and you’ll see that the en­tire dozen pa­tients have had a 97% drop in bleeds and 97% drop in the rate of in­fu­sions that had been need­ed to pro­tect them from bleeds.

From a reg­u­la­to­ry per­spec­tive, that’s a new stan­dard of care to con­sid­er. But here’s where Spark — which is go­ing right up against a more ad­vanced Bio­Marin $BM­RN pro­gram— en­coun­tered se­vere tur­bu­lence on the mar­ket side.

While 5 of the 7 pa­tients in their cho­sen dose arm have ex­pe­ri­enced FVI­II ac­tiv­i­ty lev­els be­tween 16% and 49% — hit­ting their pro­ject­ed range of 12% to 100% for up to 30 weeks — two have had set­backs. Im­mune re­spons­es caused their FVI­II lev­els to drop be­low 5%, forc­ing them to switch to on-de­mand treat­ment. One chose to go in­to the hos­pi­tal for in­fu­sions — a se­ri­ous ad­verse event. There were al­so a num­ber of ALT el­e­va­tions in pa­tients that raised con­cerns.

Of note, across the study, sev­en of the 12 par­tic­i­pants re­ceived a ta­per­ing course of oral steroids in re­sponse to an ala­nine amino­trans­ferase (ALT) el­e­va­tion above pa­tient base­line, de­clin­ing FVI­II lev­els and/or pos­i­tive IFN- en­zyme-linked im­munospots (ELISPOTs). For these sev­en par­tic­i­pants, steroids led to nor­mal­iza­tion of ALT and ELISPOTs. For all but the two above men­tioned 2×1012 vg/kg co­hort par­tic­i­pants, oral steroids led to sta­bi­liza­tion of tar­get FVI­II lev­els.

Spark’s shares plunged 29% af­ter the re­lease, which in­cludes its Q2 num­bers, hit the wire. Bio­Marin’s stock, mean­while, is up about 6.5%.

Any­time you run a Phase I/II study of a new ther­a­py like this, says the CEO, you have some learn­ing to do about safe­ty and ef­fi­ca­cy. Even with the set­backs, he adds, the two pa­tients have had good clin­i­cal out­comes, with a dra­mat­ic drop in bleeds and in­fu­sions. And with what they’ve learned from their work on he­mo­phil­ia A as well as their close­ly-watched he­mo­phil­ia B pro­gram, he added, there’s good rea­son to be­lieve they can do bet­ter in Phase III.

Up to now, though, Spark has con­tin­ued to run in­to prob­lems with in­vestors whose first re­ac­tion is to com­pare their he­mo­phil­ia A pro­gram with Bio­Marin’s. And the Bio­Marin team’s per­for­mance has been win­ning ku­dos for a sol­id set of re­spons­es in a small group of pa­tients. Mar­raz­zo al­so likes to point out that their ri­val’s per­for­mance hasn’t been per­fect ei­ther, but he’s not un­aware that the mar­ket sees this as es­sen­tial­ly a head-to-head af­fair — even if there’s no ac­tu­al head-to-head study un­der­way.

Mar­raz­zo’s view: “We’re in the ear­ly in­nings of a long game. We be­lieve with a stan­dard­ized ap­proach it will sup­port the pro­gram as we move for­ward…We’re all learn­ing this as we go,” he adds, not­ing that Spark is in a “very com­pet­i­tive race.”

He’ll be hold­ing on to that thought to­day as the mar­ket re­acts.


Im­age: Jeff Mar­raz­zo at an event in 2015. OPH­THAL­MOL­O­GY IN­NO­VA­TION SUM­MIT

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.

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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.

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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.

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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.

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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.

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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.

BeiGene and Mus­tang nail down spe­cial FDA sta­tus for top drugs; Roche bags added cov­er­age for Hem­li­bra

→ BeiGene $BGNE is getting a boost in its drive to field a rival to Imbruvica. The FDA has offered an accelerated review to zanubrutinib, a BTK inhibitor that has posted positive results for mantle cell lymphoma. The PDUFA date lands on February 27, 2020. The drug scored breakthrough status at the beginning of the year.

→ BeiGene isn’t the only biopharma company to gain special regulatory status today. Mustang Bio $MBIO and St. Jude Children’s Research Hospital announced that MB-107, a lentiviral gene therapy for the treatment of X-linked severe combined immunodeficiency, also known as bubble boy disease, has been granted Regenerative Medicine Advanced Therapy status.