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

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

CDC’s Robert Redford, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

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Stephen Hahn went before a Senate committee Wednesday and declared he’s fighting. “Every one of the decisions we have reached has been made by career FDA scientists based on science and data, not politics,” he exclaimed, adding that “FDA will not permit any pressure from anyone to change that. I will fight for science.”

A few hours later, he was undermined by President Donald Trump when a reporter asked if he was okay with stricter vaccine guidelines that the FDA was said to be cooking up. “That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” he decided.

Laura Shawver (Silverback Therapeutics)

Fol­low­ing a hefty Se­ries B, Sil­ver­back Ther­a­peu­tics quick­ly pulls in $85 mil­lion for 'an im­por­tant growth phase'

Months after reeling in a $78 million Series B round, Silverback Therapeutics has hooked an even larger Series C.

The Seattle-based company announced Wednesday that it netted $85 million from a slate of new and previous investors. The quick boost could be a sign that an IPO is on the way.

In an email, Silverback CEO Laura Shawver told me she was “not able to provide any additional comments about Silverback” beyond what was shared in the company’s news release. In the prepared statement, she said the company is at “an important growth phase.”

President Trump walks past HHS secretary Alex Azar (Getty Images)

Azar falls in line un­der Trump again. Ex­perts say he's re­in­forc­ing a dark sig­nal sent to the FDA

In the latest incident where Alex Azar has steadfastly taken the side of President Donald Trump over that of the FDA, the HHS secretary was noncommittal this morning when asked if he supports the attempt by his subordinates at the FDA to strengthen guidelines for a vaccine EUA.

Appearing on NBC’s Today Show, the HHS secretary deliberately muddied the waters, stating that the guidance that matters is the one that is “actually already out there.”

Covid-19 roundup: Op­er­a­tion Warp Speed's 7th vac­cine is live at­ten­u­at­ed; Small biotech touts big suc­cess where gi­ants have failed

Operation Warp Speed is stacking its vaccine portfolio with a “TBD” new candidate: a live attenuated vaccine that can be administered in a single dose, potentially as an oral formulation rather than an injection.

Sound familiar?

That could be because the unannounced candidate appears to match the profile of an inoculation being developed by Merck, according to Bloomberg, which first reported the development based on a presentation by Moncef Slaoui.

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News brief­ing: HHS chas­tis­es Eli Lil­ly for end­ing some dis­counts in a pan­dem­ic; Gilead to pay $97 mil­lion to set­tle kick­back al­le­ga­tions

Gilead agreed to pay $97 million to settle allegations that it illegally used a charity to pay thousands of Medicare patients’ co-payments for its pulmonary arterial hypertension drug Letairis.

The US government claimed that between June 2007 and December 2010, Gilead $GILD used the Caring Voice Coalition as a conduit to cover the costs of just its own drug. The alleged behavior goes against the False Claims Act.

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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On­ly five months af­ter a Se­ries A launch, Taysha goes pub­lic with $157M IPO

As has been the trend in 2020, Taysha Gene Therapies has become the latest biotech to make a quick ascent from a small, privately-funded company to enjoying its very own Nasdaq ticker.

The Dallas-based biotech raised $157 million for its IPO after pricing shares at $20 apiece Thursday, the high-point of its expected range. Initially pegging $100 million in financing, Taysha offered a little less than 8 million shares and will trade under the $TSHA symbol.

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CEO Markus Warmuth (Monte Rosa)

Monte Rosa rakes in $96M Se­ries B as it pre­pares 'mol­e­c­u­lar glue' plat­form for IND-en­abling stud­ies

About four months after completing an extension to its Series A, Monte Rosa Therapeutics is putting its next foot forward with another heap of cash.

The Boston-based biotech is back with $96 million in Series B financing with a goal to get its lead program ready for IND-enabling studies by the end of the year. Though Monte Rosa is keeping its specific target a secret for now, the company has been researching how to utilize its protein degradation technology in breast cancer and non-small cell lung cancer, among other areas.