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.”

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Justin Klee (L) and Joshua Cohen, Amylyx co-CEOs (Cody O'Loughlin/The New York Times; courtesy Amylyx)

Ad­vo­cates, ex­perts cry foul over Amy­lyx's new ALS drug, cit­ing is­sues with price, PhI­II com­mit­ment

Not 24 hours after earning the first ALS drug approval in five years, Amylyx Pharmaceuticals’ Relyvrio is already drawing scrutiny. And it’s coming from multiple fronts.

In an investor call Friday morning, Amylyx revealed that it would charge about $158,000 per year, a price point that immediately drew backlash from ALS advocates and some outside observers. The cost reveal had been highly anticipated in the immediate hours after Thursday evening’s approval, though Amylyx only teased Relyvrio would cost less than previously approved drugs.

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Land­mark Amy­lyx OK spurs de­bate; Some... pos­i­tive? Alzheimer's da­ta; Can­cer tri­al bot­tle­neck; Sanofi's CRISPR bet; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

After brief stops in Paris and Boston, John Carroll and the Endpoints crew are staying on the road in October with their return for a live/streaming EUBIO22 in London. The hybrid event fireside chats and panels on mRNA, oncology and the crazy public market. We hope you can join him there.

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#AAO22: J&J’s first look at com­mon eye dis­ease port­fo­lio pads the case for PhII of gene ther­a­py

CHICAGO — While the later-stage drug developers in the geographic atrophy field are near the finish line, Johnson & Johnson’s Janssen is taking a more deliberate route, with a treatment that it hopes to be a one-time fix.

The Big Pharma will take its Hemera Biosciences-acquired gene therapy into a Phase II study later this year in patients with GA, a common form of age-related macular degeneration that impacts about five million people worldwide. To get there, Janssen touted early-stage safety data at the American Academy of Ophthalmology annual conference Saturday morning, half a day after competitors Apellis and Iveric Bio revealed their own more-detailed Phase III analyses.

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Joshua Cohen (L) and Justin Klee, Amylyx co-CEOs

Up­dat­ed: Af­ter long and wind­ing road, FDA ap­proves Amy­lyx's ALS drug in vic­to­ry for pa­tients and ad­vo­ca­cy groups

For just the third time in its 116-year history, the FDA has approved a new treatment for Lou Gehrig’s disease, or ALS.

US regulators gave the thumbs-up to the drug, known as Relyvrio, in a massive win for patients and their families. The approval, given to Boston-area biotech Amylyx Pharmaceuticals, comes after two years of long and contentious debates over the drug’s effectiveness between advocacy groups and FDA scientists, following the readout of a mid-stage clinical trial in September 2020.

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Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Up­dat­ed: Al­ny­lam re­in­forces APOL­LO-B patisir­an da­ta be­fore head­ing to the FDA

Weeks after uncorking some mostly positive data for patisiran in transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy, Alnylam is bolstering its package with new exploratory and subgroup data before shipping it off to regulators.

The RNAi drug maintained “generally consistent” benefits in efficacy and quality of life across several prespecified subgroups at month 12, Alnylam announced on Friday afternoon, including age, baseline tafamidis use, ATTR amyloidosis type, baseline six-minute walk test score and others.

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Jerome Durso, Intercept Pharmaceuticals CEO

In­ter­cep­t's OCA fails a PhI­II NASH tri­al, rais­ing fresh doubts about its years­long quest for an OK

Intercept Pharmaceuticals has run into another big setback in its yearslong quest to win an approval for OCA in NASH. The biotech put out word Friday morning that its Phase III REVERSE study failed the primary endpoint for the liver disease, sending its share price into a tailspin.

There was no significant improvement in fibrosis among the patients suffering from cirrhosis who were treated with obeticholic acid, with investigators hunting for a minimum 1-stage histological improvement in the disease after 18 months of therapy.

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Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.