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

The Price of Re­lief: Ex­plor­ing So­lu­tions to the Ris­ing Costs of On­col­o­gy Drugs

In 2020, The National Cancer Institute estimated about 1.8 million new cases of cancer diagnosed in the United States, while the costs associated with treatment therapies continued to escalate. Given the current legislative climate on drug pricing, it’s never been more important to look at the evolution of drug pricing globally and control concerns of sustainable and affordable treatments in oncology.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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Susan Galbraith, AstraZeneca EVP, Oncology R&D

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After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

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The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

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Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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