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

Eli Lil­ly’s first PhI­II show­down for their $1.6B can­cer drug just flopped — what now?

When Eli Lilly plunked down $1.6 billion in cash to acquire Armo Biosciences a little more than a year ago, the stars seemed aligned in its favor. The jewel in the crown they were buying was pegilodecakin, which had cleared the proof-of-concept stage and was already in a Phase III trial for pancreatic cancer.

And that study just failed.

Lilly reported this morning that their cancer drug flopped on overall survival when added to FOLFOX (folinic acid, 5-FU, oxaliplatin), compared to FOLFOX alone among patients suffering from advanced pancreatic cancer.

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Med­ical an­i­ma­tion: Mak­ing it eas­i­er for the site and the pa­tient to un­der­stand

Medical animation has in recent years become an increasingly important tool for conveying niche information to a varied audience, particularly to those audiences without expertise in the specialist area. Science programmes today, for example, have moved from the piece-to-camera of the university professor explaining how a complex disease mechanism works, to actually showing the viewer first-hand what it might look like to shrink ourselves down to the size of an ant’s foot, and travel inside the human body to witness these processes in action. Effectively communicating a complex disease pathophysiology, or the novel mechanism of action of a new drug, can be complex. This is especially difficult when the audience domain knowledge is limited or non-existent. Medical animation can help with this communication challenge in several ways.
Improved accessibility to visualisation
Visualisation is a core component of our ability to understand a concept. Ask 10 people to visualise an apple, and each will come up with a slightly different image, some apples smaller than others, some more round, some with bites taken. Acceptable, you say, we can move on to the next part of the story. Now ask 10 people to visualise how HIV’s capsid protein gets arranged into the hexamers and pentamers that form the viral capsid that holds HIV’s genetic material. This request may pose a challenge even to someone with some virology knowledge, and it is that inability to effectively visualise what is going on that holds us back from fully understanding the rest of the story. So how does medical animation help us to overcome this visualisation challenge?

CSL ac­cus­es ri­val Pharm­ing of par­tic­i­pat­ing in a scheme to rip off IP on HAE while re­cruit­ing se­nior R&D staffer

Pharming has landed in the middle of a legal donnybrook after recruiting a senior executive from a rival R&D team at CSL. The Australian pharma giant slapped Pharming with a lawsuit alleging that the Dutch biotech’s new employee, Joseph Chiao, looted a large cache of proprietary documents as he hit the exit. And they want it all back.
Federal Judge Juan Sanchez in the Eastern District Pennsylvania court issued an injunction on Tuesday prohibiting Chiao from doing any work on HAE or primary immune deficiency in his new job and demanding that he return any material from CSL that he may have in his possession. And he wants Pharming to tell its employees not to ask for any information on the forbidden topics.
For its part, Pharming fired off an indignant response this morning denying any involvement in extracting any kind of IP from CSL, adding that it’s cooperating in the internal probe that CSL has underway.

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UP­DAT­ED: Alex­ion pays $930M to buy out Achillion and its promis­ing com­pan­ion drug to Soliris

After a series of stock-crunching setbacks over the years, Achillion enjoyed a turn in the sun a few weeks ago as the FDA blessed their lead drug danicopan (ACH-4471) — a complementary therapy for PNH patients taking Alexion’s Soliris — with a breakthrough drug designation after taking a look at some solid supporting Phase II data.

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Hal Barron, GSK's president of R&D and CSO, speaks to Endpoints News founder and editor John Carroll in London at Endpoints' #UKBIO19 summit on October 8, 2019

[Video] Cel­e­brat­ing tri­al fail­ures, chang­ing the cul­ture and al­ly­ing with Cal­i­for­nia dream­ers: R&D chief Hal Bar­ron talks about a new era at GSK

Last week I had a chance to sit down with Hal Barron at Endpoints’ #UKBIO19 summit to discuss his views on R&D at GSK, a topic that has been central to his life since he took the top research post close to 2 years ago. During the conversation, Barron talked about changing the culture at GSK, a move that involves several new approaches — one of which involves celebrating their setbacks as they shift resources to the most promising programs in the pipeline. Barron also discussed his new alliances in the Bay Area — including his collaboration pact with Lyell, which we covered here — frankly assesses the pluses and minuses of the UK drug development scene, and talks about his plans for making GSK a much more effective drug developer.

This is one discussion you won’t want to miss. Insider and Enterprise subscribers can log-in to watch the video.

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From left to right: Lilian Kim, Associate Director Business Development; John Moller, CEO; Yooni Kim, Executive Director, Asia Operations; Michelle Park, Director South Korea Operations.

Novotech CRO sees 26% growth in Asia tri­al ac­tiv­i­ty from biotechs, but still plen­ty of ca­pac­i­ty

As the Asia-Pacific clinical trials sector continues to grow rapidly, Novotech the Asia-Pacific-based CRO is seeing biotech clinical activity up by 26%. But says there is still plenty of capacity in the region that features advanced medical facilities, supportive regulatory environments, and more than 2.3 billion people, largely treatment naïve, living in urban areas.

China, South Korea and Australia have the most studies registered as recruiting or about to recruit according to ClinicalTrials.Gov.

The $102B club: The top 15 R&D spenders in the glob­al bio­phar­ma busi­ness — 2019 edi­tion

Over the past few years, the deluge of capital into biotech has helped lead to a dramatic shift in focus on new drug approvals, as startups are now able to raise enough cash to get through a pivotal and onto the market. But the top 15 players still account for $102 billion in spending, and their successes and failures continue to determine just how productive the industry is.

Recently we’ve seen a number of new R&D chiefs take their places at the Big 15, either setting the stage for a more focused R&D strategy — often playing more heavily in oncology. That’s true for AstraZeneca, which has had some landmark successes, and GSK, which is in search of its own turnaround in pharma R&D. HIV and vaccines are separate from that group, now led by Hal Barron.

I’ve made a point of watching their track record every year for more than a decade now. What follows is intended as a broad gauge of their activity. You don’t have to have a lot of major successes to score a winning record here, but it’s virtually impossible without a blockbuster or three in the pipeline.

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Andrew Dickinson, Gilead

Gilead­'s chief strat­e­gy ex­ec gets a big pro­mo­tion af­ter or­ches­trat­ing multi­bil­lion-dol­lar deals

After gaining credit as the architect of Gilead’s $12 billion Kite buyout as well as the recent $5 billion partnership with Galapagos, chief strategy officer Andrew Dickinson is being promoted to the prestigious CFO post at the big biotech. And new CEO Daniel O’Day says the latest move completes his makeover of the top team.
Dickinson will remain in charge of strategy in his new post.
A 3-year veteran at Gilead, Dickinson joined the bellwether biotech after a lengthy stint at Lazard Frères & Co, where he was global co-head of healthcare investing. Before that, ironically enough, he had been at Myogen, which was bought out by Gilead in 2006. Now he’ll be primarily responsible for building confidence in the numbers at a company that has a strong foundation in HIV, a disappearing franchise in hep C and a CAR-T subsidiary in Kite that has a long way to go in establishing a new business.

That big neu­ro­sciences R&D group Eli Lil­ly built is be­ing dis­man­tled, with lay­offs and parts shipped home

Seven years after Eli Lilly bulked up its neurosciences research group in Surrey and heralded the move as an indication of its commitment to the field, the pharma giant is shutting down and locking up labs.

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