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.”

Paul Hudson, Sanofi CEO (Getty Images)

Sanofi CEO Paul Hud­son has $23B burn­ing a hole in his pock­et. And here are some hints on how he plans to spend that

Sanofi has reaped $11.1 billion after selling off a big chunk of its Regeneron stock at $515 a share. And now everyone on the M&A side of the business is focused on how CEO Paul Hudson plans to spend it.

After getting stung in France for some awkward politicking — suggesting the US was in the front of the line for Sanofi’s vaccines given American financial support for their work, versus little help from European powers — Hudson now has the much more popular task of managing a major cash cache to pull off something in the order of a big bolt-on. Or two.

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As­traZeneca trum­pets the good da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Pablo Legorreta, founder and CEO of Royalty Pharma AG, speaks at the annual Milken Institute Global Conference in Beverly Hills, California (Patrick T. Fallon/Bloomberg via Getty Images)

Cap­i­tal­iz­ing Pablo: The world’s biggest drug roy­al­ty buy­er is go­ing pub­lic. And the low-key CEO di­vulges a few se­crets along the way

Pablo Legorreta is one of the most influential players in biopharma you likely never heard of.

Over the last 24 years, Legorreta’s Royalty Pharma group has become, by its own reckoning, the biggest buyer of drug royalties in the world. The CEO and founder has bought up a stake in a lengthy list of the world’s biggest drug franchises, spending $18 billion in the process — $2.2 billion last year alone. And he’s become one of the best-paid execs in the industry, reaping $28 million from the cash flow last year while reserving 20% of the cash flow, less expenses, for himself.

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The Avance Clinical leadership team: CEO Yvonne Lungershausen, Sandrien Louwaars - Director Business Development Operations, Gabriel Kremmidiotis - Chief Scientific Officer, Ben Edwards - Chief Strategy Officer

How Aus­tralia De­liv­ers Rapid Start-up and 43.5% Re­bate for Ear­ly Phase On­col­o­gy Tri­als

About Avance Clinical

Avance Clinical is an Australian owned Contract Research Organisation that has been providing high-quality clinical research services to the local and international drug development industry for 20 years. They specialise in working with biotech companies to execute Phase 1 and Phase 2 clinical trials to deliver high-quality outcomes fit for global regulatory standards.

As oncology sponsors look internationally to speed-up trials after unprecedented COVID-19 suspensions and delays, Australia, which has led the world in minimizing the pandemic’s impact, stands out as an attractive destination for early phase trials. This in combination with the streamlined regulatory system and the financial benefits including a very favourable exchange rate and the R & D cash rebate makes Australia the perfect location for accelerating biotech clinical programs.

Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: Gilead leas­es part­ner rights to TIG­IT, PD-1 in a $2B deal with Ar­cus. Now comes the hard part

Gilead CEO Dan O’Day has brokered his way to a PD-1 and lined up a front row seat in the TIGIT arena, inking a deal worth close to $2 billion to align the big biotech closely with Terry Rosen’s Arcus. And $375 million of that comes upfront, with cash for the buy-in plus equity, along with $400 million for R&D and $1.22 billion in reserve to cover opt-in payments and milestones..

Hotly rumored for weeks, the 2 players have formalized a 10-year alliance that starts with rights to the PD-1, zimberelimab. O’Day also has first dibs on TIGIT and 2 other leading programs, agreeing to an opt-in fee ranging from $200 million to $275 million on each. There’s $500 million in potential TIGIT milestones on US regulatory events — likely capped by an approval — if Gilead partners on it and the stars align on the data. And there’s another $150 million opt-in payments for the rest of the Arcus pipeline.

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Roger Perlmutter, Merck R&D chief (YouTube)

UP­DAT­ED: Backed by BAR­DA, Mer­ck jumps in­to Covid-19: buy­ing out a vac­cine, part­ner­ing on an­oth­er and adding an­tivi­ral to the mix

Merck execs are making a triple play in a sudden leap into the R&D campaign against Covid-19. And they have more BARDA cash backing them up on the move.

Tuesday morning the pharma giant simultaneously announced plans to buy an Austrian biotech that has been working on a preclinical vaccine candidate, added a collaboration on another vaccine with the nonprofit IAVI and inked a deal with Ridgeback Biotherapeutics on an early-stage antiviral.

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Bryan Roberts, Venrock

Ven­rock sur­vey shows grow­ing recog­ni­tion of coro­n­avirus toll, wan­ing con­fi­dence in ar­rival of vac­cines and treat­ments

When Venrock partner Bryan Roberts went to check the results from their annual survey of healthcare leaders, what he found was an imprint of the pandemic’s slow arrival in America.

The venture firm had sent their form out to hundreds of insurance and health tech executives, investors, officials and academics on February 24 and gave them two weeks to fill it out. No Americans had died at that point but the coronavirus had become enough of a global crisis that they included two questions about the virus, including “Total U.S. deaths in 2020 from the novel coronavirus will be:”.

Bris­tol My­ers Squibb fi­nal­ly gets in the front­line NSCLC game dom­i­nat­ed by Mer­ck, adding a sec­ond Op­di­vo/Yer­voy-based op­tion

Bristol Myers Squibb may be trailing Merck and Roche in the checkpoint race to treat frontline cases of non-small cell lung cancer, but as it does, it makes sure to bring its best feet forward.

Just days after scoring a landmark NSCLC approval for Opdivo and Yervoy alone for PD-L1 positive patients, the company said the FDA has also OK’d using the two agents with a limited course of chemo regardless of the biomarker status.

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David Hoey (Vaxxas)

In for the long vac­cine game, Mer­ck buys in­to patch de­liv­ery tech with pan­dem­ic po­ten­tial

When Merck dived into the R&D fray for a Covid-19 vaccine earlier this week, execs made it clear that they’re not necessarily looking to be first — with CEO Ken Frazier throwing cold water on the hotly-discussed 12- to 18-month timelines. But when it does emerge from behind, the pharma giant clearly expects to play a significant part.

Part of that will depend on next-generation delivery technology that reshapes the world’s imagination of a vaccine.