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.”

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

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As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

UP­DAT­ED: Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Bax­ter con­tin­ues on-shoring push with $50M In­di­ana ex­pan­sion

It’s been a banner year for the once humdrum business of manufacturing drugs, particularly vaccines. Billions have been spent ramping up facilities for Covid-19 jabs, while individual CDMOs have expanded their facilities, apparently anticipating demand or responding to a government-led push to onshore drug manufacturing.

Now Baxter Biopharma Solutions, the CDMO wing of the many-armed healthcare giant Baxter, is getting in on the game. On Tuesday, they announced plans to spend $50 million to expand their flagship, 600,000 square-foot facility in Bloomington, IN.

Eu­ro­pean Union aims to es­tab­lish patent workaround in case of emer­gen­cies while try­ing to strength­en its own IP

The European Union is looking at ways to bypass patent protections and make it easier to make generic drugs in cases of emergency such as the Covid-19 pandemic, a new document says.

Normally, under WTO regulations, the practice known as “compulsory licensing” is allowed in exceptional circumstances and could be applied as a waiver to bypass patent holders. Wednesday’s document was published as part of the EU’s plan to shore up the intellectual property rights of its member states.

Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

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Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.

Pur­due Phar­ma pleads guilty in fed­er­al Oxy­Con­tin probe, for­mal­ly rec­og­niz­ing it played a part in the opi­oid cri­sis

Purdue Pharma, the producer of the prescription painkiller OxyContin, admitted Tuesday that, yes, it did contribute to America’s opioid epidemic.

The drugmaker formally pleaded guilty to three criminal charges, the AP reported, including getting in the way of the DEA’s efforts to combat the crisis, failing to prevent the painkillers from ending up on the black market and encouraging doctors to write more painkiller prescriptions through two methods: paying them in a speakers program and directing a medical records company to send them certain patient information. Purdue’s plea deal calls for $8.3 billion in criminal fines and penalties, but the company is only liable for a fraction of that total — $225 million.