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

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

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No­var­tis de­vel­op­ment chief John Tsai: 'We go deep in the new plat­form­s'

During our recent European Biopharma Summit, I talked with Novartis development chief John Tsai about his experiences over the 3-plus years he’s been at the pharma giant. You can read the transcript below or listen to the exchange in the link above.

John Carroll: I followed your career for quite some time. You’ve had more than 20 years in big pharma R&D and you’ve obviously seen quite a lot. I really was curious about what it was like for you three and a half years ago when you took over as R&D chief at Novartis. Obviously a big move, a lot of changes. You went to work for the former R&D chief of Novartis, Vas Narasimhan, who had his own track record there. So what was the biggest adjustment when you went into this position?

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Susan Galbraith, Executive VP, Oncology R&D, AstraZeneca

As­traZeneca on­col­o­gy R&D chief Su­san Gal­braith: 'Y­ou're go­ing to need or­thog­o­nal com­bi­na­tion­s'

 

Earlier in the week we broadcast our 4th annual European Biopharma Summit with a great lineup of top execs. One of the one-on-one conversations I set up was with Susan Galbraith, the oncology research chief at AstraZeneca. In a wide-ranging discussion, Galbraith reviewed the cancer drug pipeline and key trends influencing development work at the pharma giant. You can watch the video, above, or stick with the script below. — JC

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Amit Etkin, Alto Neuroscience CEO (Alto via Vimeo)

A star Stan­ford pro­fes­sor leaves his lab for a start­up out to re­make psy­chi­a­try

About five years ago, Amit Etkin had a breakthrough.

The Stanford neurologist, a soft-spoken demi-prodigy who became a professor while still a resident, had been obsessed for a decade with how to better define psychiatric disorders. Drugs for depression or bipolar disorder didn’t work for many patients with the conditions, and he suspected the reason was how traditional diagnoses didn’t actually get at the heart of what was going on in a patient’s brain.

Roche's Tecen­triq cross­es the fin­ish line first in ad­ju­vant lung can­cer, po­ten­tial­ly kick­ing off gold rush

While falling behind the biggest PD-(L)1 drugs in terms of sales, Roche has looked to carve out a space for its Tecentriq with a growing expertise in lung cancer. The drug will now take an early lead in the sought-after adjuvant setting — but competitors are on the way.

The FDA on Friday approved Tecentriq as an adjuvant therapy for patients with Stage II-IIIA non small cell lung cancer with PD-(L)1 scores greater than or equal to 1, making it the first drug of its kind approved in an early setting that covers around 40% of all NSCLC patients.

Susan Galbraith speaking at Endpoints News' virtual EUBIO21 summit

Imfinzi/treme­li­mum­ab com­bo scores As­traZeneca an­oth­er OS win — this time in liv­er can­cer

Is the tide turning on AstraZeneca’s battered PD-L1/CTLA4 combo?

A single priming dose of the experimental tremelimumab, followed by Imfinzi every four weeks, beat Nexavar (sorafenib) in helping a group of liver cancer patients live longer in a Phase III study, the company reported, meeting the primary endpoint.

Specifically, the two drugs extended overall survival for patients with unresectable hepatocellular carcinoma who had not received prior systemic therapy and were not eligible for localized treatment.

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FDA+ roundup: Marks on Wood­cock­'s tenure as act­ing com­mis­sion­er; FDA lead­ers of­fer per­spec­tive on bar­ri­ers to di­ver­si­ty in re­search

CBER director Peter Marks praised Janet Woodcock’s work as acting FDA commissioner, and while noting that Biden needs to nominate someone to fill the role permanently by Nov. 16, he said he has “no idea” when that actually might occur.

“Dr. Woodcock has been at the agency for over three decades and she, during that time, has proven herself to be a remarkably capable manager,” Marks said at the Alliance for Regenerative Medicine’s meeting Tuesday. “And she’s been managing as if she’s commissioner, unlike some previous acting [commissioners] who are afraid to actually do things. She doesn’t appear to be afraid to do things. I have not felt any different now from when we had a commissioner in place,” he added.

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FDA ad­comm votes unan­i­mous­ly in sup­port of a J&J Covid-19 boost­er two months af­ter one-dose shot

The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Friday voted 19-0 in favor of authorizing a second shot of J&J’s Covid-19 vaccine to follow at least two months after the initial dose.

Regulators don’t have to follow VRBPAC’s recommendation, but they almost always do. Considering that the CDC’s advisory committee has already been set to review the expanded EUA, VRBPAC’s recommendation is likely to be adopted.