No­var­tis shoots for ear­ly OK of a ‘break­through’ blood can­cer drug af­ter re­vers­ing or­gan dam­age in tri­al

Up to now, No­var­tis’ mi­dostau­rin has been pri­mar­i­ly not­ed for its po­ten­tial in treat­ing a mu­ta­tion-spe­cif­ic type of acute myeloid leukemia, thrust in­to the spot­light af­ter the FDA hand­ed out its break­through des­ig­na­tion for the drug ear­li­er this year. But a new study shows that the drug al­so demon­strat­ed a sta­tis­ti­cal­ly sig­nif­i­cant abil­i­ty to halt and re­verse or­gan dam­age caused by rare cas­es of ad­vanced sys­temic mas­to­cy­to­sis. And the phar­ma gi­ant now plans to prep an ap­pli­ca­tion for reg­u­la­tors on both sides of the At­lantic in search of ear­ly mar­ket­ing ap­proval.

There are var­i­ous kinds of mas­to­cy­to­sis, which is char­ac­ter­ized by an over ac­cu­mu­la­tion of mast cells in tis­sue. But ad­vanced sys­temic mas­to­cy­to­sis threat­ens or­gan dam­age and death and one form – mast-cell leukemia – is in­vari­ably lethal.

Ja­son R. Gotlib, MD – Stan­ford Uni­ver­si­ty

“Mi­dostau­rin (PKC412) is a mul­ti­k­i­nase in­hibitor, so it has sev­er­al mol­e­c­u­lar tar­gets,” Ja­son Gotlib, the lead in­ves­ti­ga­tor from Stan­ford, tells me. That makes it right for AML pa­tients with a FLT-3 mu­ta­tion. It al­so in­hibits KIT D816V, a pro­tein in the ty­ro­sine ki­nase fam­i­ly which dri­ves the de­vel­op­ment of mast cells.

To test it, in­ves­ti­ga­tors re­cruit­ed 116 pa­tients in an open-la­bel study, with­out a con­trol arm, in­clud­ing 89 with dis­ease-re­lat­ed or­gan dam­age. 16 of the pa­tients had the most ag­gres­sive form of the dis­ease.

“Noth­ing works for them,” says Gotlib. But 8 of the 16 re­spond­ed to the drug and “7 had com­plete res­o­lu­tion of or­gan dam­age” as­so­ci­at­ed with longer sur­vival.

The over­all re­sponse rate Gotlib and his team tracked was 60%, with 45% of the pa­tients achiev­ing a “ma­jor re­sponse,” de­fined as  the com­plete res­o­lu­tion of at least one type of mas­to­cy­to­sis-re­lat­ed or­gan dam­age.

The me­di­an over­all sur­vival rate tracked in the study was 28.7 months, with the 16 mast-cell leukemia pa­tients achiev­ing a me­di­an OS rate of 9.4 months. But with­out a con­trol arm, there’s no way to de­ter­mine from this study if pa­tients gained a sur­vival ad­van­tage.

Even with­out a con­trol arm in the study, though, Gotlib says the im­pact on or­gan dam­age and the ab­sence of any ef­fec­tive ther­a­pies for the rare con­di­tion make it ap­pro­pri­ate to seek out ac­cel­er­at­ed ap­proval on the Phase II da­ta. And a spokesper­son for No­var­tis con­firmed that the Big Phar­ma play­er is al­so ready­ing its ap­pli­ca­tion for FLT-3 mu­tat­ed AML.

“This is a drug that works,” Dr. Robert Hro­mas from the Uni­ver­si­ty of Flori­da told the UPI. “And un­til now, we’ve re­al­ly had noth­ing.”

Hro­mas was not part of the study.

“Pa­tients with ad­vanced SM are part of a very small, high­ly un­der­served com­mu­ni­ty that has suf­fered from a lack of med­ical in­no­va­tion for many years,” said Alessan­dro Ri­va, the glob­al head of No­var­tis On­col­o­gy De­vel­op­ment and Med­ical Af­fairs. “No­var­tis…is now work­ing with reg­u­la­to­ry au­thor­i­ties to make mi­dostau­rin avail­able as quick­ly as pos­si­ble.”

In­side Track: Be­hind the Scenes of a Ma­jor Biotech SPAC

Dr. David Hung and Michelle Doig are no strangers to the SPAC phenomenon. As Founder and CEO of Nuvation Bio, a biotech company tackling some of the greatest unmet needs in oncology, Dr. Hung recently took the company public in one of this year’s biggest SPAC related deals. And as Partner at Omega Funds, Doig not only led and syndicated Nuvation Bio’s Series A, but is now also President of the newly formed, Omega-sponsored, Omega Alpha SPAC (Nasdaq: OMEG; oversubscribed $138m IPO priced January 6, 2021).

Hal Barron, GSK R&D chief (Endpoints News)

Hal Bar­ron gam­bles $625M cash on high-wire TIG­IT act, throw­ing Glax­o­SmithK­line in­to heat­ed race and com­plet­ing next-gen I/O trin­i­ty

Count Hal Barron and GlaxoSmithKline in for the TIGIT fight.

The stakes are as high as the risks: While a growing pack of Big Pharma rivals is lending credence to the hypothesis that TIGIT will be the next big immune checkpoint and cancer drug target, the first clinical trials have shown response rates that can be described as modest at best. But Barron’s bet is on the whole “axis” that the receptor sits on, with an eye on testing its new anti-TIGIT antibody not just in combo with PD-1 but also in triplets.

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As Covid-19 shifts the world's at­ten­tion to biotech, Noubar Afeyan's Flag­ship builds $3.4B fund to fu­el new in­ven­tions. Here's the plan

A little more than a year ago, Flagship Pioneering rolled out a monster fund with $1.1 billion in it to bankroll the platform companies they were creating inside their own labs. But it turns out, that was just the prelude to a much, much larger raise, as both current investors — who’ve been reaping the rewards of some booming biotech stocks — join in with new investors betting on more in the years to come.

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Bio­gen sig­nals a big PhI­II fail­ure as the lead gene ther­a­py in their $800M Night­star buy­out goes down in flames

That $800 million buyout of Nightstar has turned into a bust for Biogen as the lead therapy in the deal failed a pivotal study, signaling a severe setback for the biotech’s ambitions in gene therapies.

The big biotech put out the word after the market closed on Monday that the gene therapy they picked up in the deal for a degenerative blindness called choroideremia failed the Phase III study, just a month after their #2 drug in the deal also flopped in a mid-stage study.

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Geoffrey Porges, SVB Leerink

Top an­a­lyst maps a rocky road for Ver­tex — un­less they adopt a $10B M&A cam­paign to save the pipeline

After repeatedly poking Vertex $VRTX execs with pointed criticism of their R&D strategy, top SVB Leerink analyst Geoffrey Porges is now turning up the heat to a full-scale roasting.

In a note out early Monday morning, Porges spotlights the impact of Vertex’s recent follow-up failure on AATD — their treatment hit the endpoint but missed on commercial prospects — rewriting his recommended scenario for CEO Reshma Kewalramani as she grapples with the setback.

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Stephen Hahn (AP Images)

UP­DAT­ED: Ex-FDA com­mish Stephen Hahn joins Flag­ship, a ven­ture group that spawned Covid-19 vac­cine mak­er Mod­er­na

That revolving door between the FDA and industry is spinning even faster than usual.

Former FDA commissioner Stephen Hahn is joining Flagship Pioneering, the venture outfit that founded Moderna — which raced its way to an FDA EUA for a Covid-19 vaccine that is making billions of dollars– as the new CMO of its Preemptive Medicine and Health Security initiative.

Flagship confirmed the hire — first reported in The Washington Post — in a statement out late Monday.

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Patrizia Cavazzoni, CDER

FDA’s Cavaz­zoni calls for ad­comms to ‘get back to the sub­stance’

While her comments were recorded prior to the FDA’s recent approval of Biogen’s controversial Alzheimer’s drug, CDER Director Patrizia Cavazzoni presciently called for substantiating reforms to the advisory committee process at the agency.

Short on examples, Cavazzoni said at a BIO event aired on Monday that some recent adcomms show “how they can be swayed by emotion in the face of hard facts,” but they need to “get back to the fundamentals, which is listening to thoughtful input from experts in response to thoughtful questions that we ask them.”

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Terns Phar­ma­ceu­ti­cals touts safe­ty da­ta from an ex-Eli Lil­ly can­di­date in the hunt for NASH treat­ment

While many others have tried — and failed — to get a NASH candidate across the finish line, Terns Pharmaceuticals thinks its FXR agonist will eventually earn its wings without the safety issues that have slowed others down. Now, a mid-stage safety readout could help add some validity to those hopes.

No patients in the Phase IIa LIFT study discontinued TERN-101 due to side effects, CMO Erin Quirk said during a call with investors on Monday morning. That includes pruritus, an uncomfortable itching sensation that frequently leads patients to drop out of other FXR agonist studies.

David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

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