Spark Ther­a­peu­tics faces a grilling as FDA pon­ders a pi­o­neer­ing OK for gene ther­a­py

With one of the most close­ly-watched FDA pan­el re­views of the year com­ing up for Spark Ther­a­peu­tics’ $ONCE lead gene ther­a­py, in­ter­nal re­view­ers at the FDA have raised some se­ri­ous ques­tions for the ex­perts to con­sid­er.

At the top of the heap of con­sid­er­a­tions the pan­el ex­perts will field on Thurs­day are ques­tions about the dura­bil­i­ty of this eye ther­a­py, the pos­si­bil­i­ty that pa­tients will need mul­ti­ple treat­ments in or­der to pre­serve vi­sion gains, the right age to use it and the use of a com­plete­ly nov­el end­point for the pri­ma­ry goal when stan­dard vi­su­al acu­ity achieve­ments fell far short of the goal on sta­tis­ti­cal sig­nif­i­cance.

The re­view­ers read­i­ly agree that the gene ther­a­py — an­gling to be­come the first such treat­ment ap­proved in the US — met the main cri­te­ria for suc­cess. But the drug, voreti­gene nepar­vovec (or Lux­tur­na), al­so was no once-and-done panacea.

In­vestors were up­beat but pos­si­bly a lit­tle am­biva­lent about the next step, with Spark’s stock up 1% in pre-mar­ket trad­ing.

In the key study, in­ves­ti­ga­tors treat­ed 21 pa­tients with reti­nal dy­s­tro­phy trig­gered by bial­lel­ic RPE65 mu­ta­tions; 10 were re­cruit­ed for the place­bo group. Eleven of the 21 had a sig­nif­i­cant, two point or more im­prove­ment in light lev­els in both eyes, with 15 scor­ing a sig­nif­i­cant MLMT (mul­ti-lu­mi­nance mo­bil­i­ty test­ing) gain in the first treat­ed eye. That eas­i­ly beat the re­sponse in the con­trol arm.

Check­ing vi­su­al acu­ity, though, shows that the pa­tients failed to demon­strate a sig­nif­i­cant im­prove­ment for the des­ig­nat­ed sec­ondary, leav­ing Spark to seek a pi­o­neer­ing ap­proval us­ing an end­point that’s nev­er been used be­fore in this way.

The FDA is ask­ing the ex­perts to con­sid­er the sig­nif­i­cance of the end­point, the im­pact such im­prove­ments have on pa­tients’ dai­ly ac­tiv­i­ties, as well as the con­se­quences if pa­tients need mul­ti­ple treat­ments, giv­en the fact that there’s no da­ta on just how durable the treat­ment ef­fect can be.

Notes the re­view:

(T)here is no avail­able long term fol­low up da­ta to ad­dress whether the ef­fect de­cays over time. There­fore, the du­ra­tion of AAV2- me­di­at­ed trans­gene ex­pres­sion lead­ing to sus­tained clin­i­cal ben­e­fits be­yond one year is un­clear.

The re­view al­so notes that Spark ig­nored a key piece of ad­vice, avoid­ing a co-pri­ma­ry end­point on eval­u­at­ing how the first-treat­ed eye was af­fect­ed com­pared to both eyes, with re­view­ers con­cerned that a pa­tient re­sponse could be judged a suc­cess even if vi­sion in one eye de­te­ri­o­rat­ed and on­ly one eye im­proved.

This con­cern led FDA to rec­om­mend co-pri­ma­ry ef­fi­ca­cy end­points, i.e., MLMT score change us­ing both eyes and MLMT score change us­ing the first eye. How­ev­er, Study 301 was de­signed with a sin­gle pri­ma­ry end­point, an MLMT score change us­ing both eyes.

None of that marks a kiss of death for this ap­pli­ca­tion. The re­view­ers are care­ful to avoid any harsh judg­ments or en­dorse­ments, stay­ing neu­tral on the key ques­tions re­gard­ing ef­fi­ca­cy and safe­ty. But it’s al­so not ex­act­ly the kind of dis­cus­sion any gene ther­a­py com­pa­ny wants to have just be­fore a po­ten­tial mar­ket launch like this.

While an­a­lysts have giv­en Spark high marks for this ther­a­py, with good odds of suc­cess, ma­jor ques­tions re­main on how these treat­ments will be cov­ered by skep­ti­cal pay­ers who may be asked to foot the bill on a mil­lion-dol­lar pro­ce­dure. Will the pay­ments be spread over time? And what hap­pens if the gene ther­a­py doesn’t work as billed, or fades over time?

RBC’s Matthew Eck­ler count­ed him­self among the an­a­lysts who saw to­day’s re­view, with no big sur­pris­es, as a plus for Spark. He not­ed:

On first read, we see no ma­jor sur­pris­es in FDA brief­ing doc­u­ments re­leased this morn­ing ahead of Thurs­day’s Ad­Com meet­ing for Lux­tur­na. Fo­cus of the FDA re­view is on ef­fi­ca­cy (younger vs old­er pa­tients, nov­el Phase III end­point), safe­ty (sub­reti­nal in­jec­tion, im­muno­genic­i­ty), and du­ra­tion of re­sponse; while the sin­gle vot­ing ques­tion sets up a straight up/down vote. As out­lined in our re­cent ini­ti­a­tion (link), we an­tic­i­pate a pos­i­tive pan­el and ap­proval by the 1/12/18 PDU­FA. Sep­a­rate­ly, we see dis­cus­sion and out­come Thurs­day as hav­ing read-through to the gene ther­a­py space broad­ly, par­tic­u­lar­ly FDA and pan­el mem­bers’ fo­cus/com­fort around safe­ty and du­ra­tion of re­sponse.

So far, two gene ther­a­pies have been ap­proved in Eu­rope, but the first one flat failed to gain trac­tion and was dumped while the sec­ond is on­ly rarely em­ployed. With this first ap­pli­ca­tion in the US, Spark is ini­ti­at­ing a dis­cus­sion that will be close­ly fol­lowed through­out the in­dus­try.

The out­come is not as­sured.

Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

Daniel O'Day [via AP Images]

UP­DAT­ED: Gilead un­leash­es a $5B late-stage cash al­liance with Gala­pa­gos — lay­ing out O'­Day's R&D strat­e­gy

Daniel O’Day is executing his first major development deal since taking over as CEO of Gilead $GILD. And he’s going in deep to ally himself with a longstanding partner.

O’Day announced today that he is spending $5 billion in cash to add new late-stage drugs to Gilead’s pipeline, picking up rights to Galapagos’ $GLPG Phase III IPF drug GLPG1690 alongside adoption of the biotech’s Phase IIb drug GLPG1972 for osteoarthritis. And Gilead is also putting billions more on the table for milestones, gaining options for everything else in Galapagos’ pipeline, with a shot at all rights outside of Europe.

Altogether, Gilead is gaining rights to 6 clinical-stage assets, 20 preclinical programs and everything else being hatched in translation.

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Hal Bar­ron's team at GSK scores a win with pos­i­tive Ze­ju­la PhI­II front­line study — now comes the hard part

Score one for Hal Barron and the new R&D team steering GlaxoSmithKline’s pipeline.

The pharma giant reported this morning that its recently acquired PARP, Zejula (niraparib), hit the primary endpoint on progression-free survival in a frontline maintenance setting for women suffering ovarian cancer — following chemo and regardless of their BRCA status.

GSK bet $5 billion on the Tesaro buyout primarily to get this drug, drawing the shaking heads of biopharma. Why pay a big premium for a drug like this when AstraZeneca was going from strength to strength with Lynparza, ran the argument, having won a hugely important accelerated approval to jump out ahead — way ahead — of the rest of the PARP players? Lynparza — now co-owned by a powerhouse cancer team at Merck — won the first approval in frontline maintenance in ovarian cancer.

Alk­er­mes adds bipo­lar I dis­or­der to its FDA wish­list; Con­go con­firms first Ebo­la case in large city

→ An ever-ambitious Alkermes $ALKS team plans to add bipolar I disorder to its list of conditions for ALKS-3831, which it plans to pitch to the FDA in Q4. Alkermes says they were persuaded to add bipolar I disorder after a pre-NDA meeting with the agency, which came about 7 months after the biotech reported positive data for schizophrenia. The drug is a combo using olanzapine/samidorphan, which they hope will be shown to be as effective as olanzapine without the substantial increase in the risk of weight gain.

Pe­ter Kolchin­sky and Raj Shah raise a $300M fund de­vot­ed to biotech star­tups

Peter Kolchinsky and Raj Shah have another $300 million-plus to play with on the biotech venture side of their investment business. 

The two announced Monday morning that they’ve put together their first pure-play venture fund at RA Capital Management, which has been known to bet on just about every angle in healthcare investing — from rounds to follow-on investments at public companies. This new fund of theirs arrives well into a go-go era of new startup financing, with a particular focus on building new biotechs.

Boehringer buys Swiss biotech in its lat­est M&A deal, go­ing the next-gen can­cer vac­cine route

Boehringer Ingelheim has snapped up a Swiss biotech startup and added their group as a new platform for the oncology pipeline. 

The German biopharma company has bagged Geneva-based AMAL Therapeutics, paying out an unspecified upfront in a $358 million deal — cash, milestones and everything else, all in. Plus there’s 100 million euros on the line for commercial milestones.

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Ab­b­Vie beefs up the on­col­o­gy pipeline, bag­ging an up­start STING play­er with its own unique ap­proach

AbbVie isn’t letting its $63 billion buyout of Allergan stop its M&A/deals team from continuing their work.

Monday morning we learned that the pharma giant is snapping up tiny Mavupharma out of Seattle, a Frazier-backed startup that has its own unique take on STING — which is on the threshold of their first clinical trial.

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Billing it­self as the first AI biotech to launch hu­man tri­als, Re­cur­sion adds $121M C round

Billing itself as the first AI biotech with programs in the clinic, Salt Lake City-based Recursion now has a $121 million bankroll to start gathering human data to see if it’s on the right track. 

“We’re trying to build this discovery engine,” Recursion CEO Chris Gibson tells me ahead of the C round news. “We now have the first two programs in the clinic.” And that, he adds, qualifies as a first for any AI establishment “that actually have something in the clinic.”

FDA bats back As­traZeneca's SGLT di­a­betes drug for Type 1 di­a­betes — block­ing a class on safe­ty fears

The FDA has just fired its latest salvo at the SGLT class of diabetes drugs, blowing up some commercial opportunity at AstraZeneca as part of the collateral damage.

The pharma giant reported early Monday that the FDA has rejected its blockbuster drug Farxiga for Type 1 diabetes that can’t be controlled by insulin. And while the pharma giant maintained its usual grim silence in the face of a setback, this one should be easy to interpret.