EMA im­pos­es for­mal lim­it on Xel­janz pre­scrip­tion as reg­u­la­tors con­tin­ue to re­view safe­ty con­cerns

Three months af­ter Pfiz­er flagged blood clot is­sues and a high­er rate of deaths for rheuma­toid arthri­tis pa­tients tak­ing the 10 mg dose of Xel­janz (to­fac­i­tinib) in a post-mar­ket­ing safe­ty study, the EMA has hand­ed down of­fi­cial re­stric­tions in its use.

The agency’s safe­ty com­mit­tee — phar­ma­covig­i­lance risk as­sess­ment com­mit­tee, or PRAC — is still in the process of re­view­ing the ev­i­dence, but it is alarmed enough to ban pre­scrip­tion of the 10 mg twice dai­ly reg­i­men in any pa­tients with a high risk of blood clots in the lungs. Those who have heart fail­ure, can­cer, a his­to­ry or pre­dis­po­si­tion to blood clots are on the list, as are pa­tients tak­ing hor­mone-based ther­a­pies or prepar­ing/re­cov­er­ing from ma­jor surgery.

And reg­u­la­tors made sure to be crys­tal clear about the im­pli­ca­tions:

The new ad­vice means that, since 10 mg is the on­ly rec­om­mend­ed start­ing dose for ul­cer­a­tive col­i­tis, pa­tients with this con­di­tion who are at high risk of blood clots must not be start­ed on Xel­janz. Pa­tients at high risk cur­rent­ly tak­ing this dose for any con­di­tion must be switched to al­ter­na­tive treat­ments.

The for­mal — though tem­po­rary — re­stric­tions fol­low an ear­li­er warn­ing, which di­rect­ed health­care pro­fes­sion­als to mon­i­tor pa­tients for signs and symp­toms of blood clots in the lungs. Doc­tors were al­so ad­vised to stick to the rec­om­mend­ed 5 mg dose when treat­ing rheuma­toid arthri­tis.

In Feb­ru­ary, Pfiz­er yanked the 10 mg dose from the on­go­ing A3921133 study in rheuma­toid arthri­tis, switch­ing pa­tients to the 5 mg dose af­ter doc­u­ment­ing “a sta­tis­ti­cal­ly and clin­i­cal­ly im­por­tant dif­fer­ence in the oc­cur­rence of pul­monary em­bolism” as well as an im­bal­ance in the rate of death. In ad­di­tion to the 5 mg arm, there was al­so a con­trol group tak­ing a TNF in­hibitor.

The FDA sound­ed its own alarm days lat­er, launch­ing an in­ves­ti­ga­tion and urg­ing pa­tients to seek med­ical care if they ex­pe­ri­ence a blood clot in the lung, chest pains, or start cough­ing up blood.

Xel­janz was the orig­i­nal JAK in­hibitor to hit the mar­ket, rack­ing up block­buster sales in the sev­en years it’s been ap­proved by the FDA (the EMA nod came much lat­er in 2017). But safe­ty is­sues have cloud­ed both the drug and the en­tire class, as man­i­fest­ed by the FDA’s de­ci­sion to slap down a high­er, 4 mg dose of Eli Lil­ly’s Olu­mi­ant (baric­i­tinib) and al­low on­ly the 2 mg dose in the mar­ket.

None of that has stopped Pfiz­er from step­ping up its JAK game, though. Just this week, the phar­ma gi­ant tout­ed a pos­i­tive slate of Phase III da­ta for its JAK1 in­hibitor abroc­i­tinib (PF-​04965842) in atopic der­mati­tis, look­ing to get in­to a heat­ed block­buster race.

Ab­b­Vie’s own JAK1, upadac­i­tinib, is now un­der reg­u­la­to­ry re­view for rheuma­toid arthri­tis on both sides of the At­lantic. Gilead put its bet on fil­go­tinib, wide­ly tapped as a po­ten­tial block­buster in its own right. Both com­pa­nies are giv­ing them­selves high marks on safe­ty, sig­nal­ing a fierce mar­ket­ing ri­val­ry to come.


Im­age Source: Pfiz­er

Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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George Yancopoulos (Regeneron)

Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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No­var­tis los­es biosim­i­lar ap­peal as court up­holds a 31-year mo­nop­oly by Am­gen's En­brel

A new court ruling has strengthened Amgen’s grip on the IP estate around Enbrel, keeping biosimilars of the autoimmune and inflammatory drug at bay until 2029.

Novartis, the patent challenger, isn’t throwing in the towel yet. In a statement noting the failed appeal, its generics division Sandoz noted its reviewing options, “including potential appeal to US Supreme Court.”

It’s been almost four years since the FDA approved Erelzi, Sandoz’s copycat version of Enbrel. While sales of the Pfizer-partnered drug in the US — the market Amgen is in charge of — have dipped slightly during that time, it remains a solid megablockbuster with 2019 revenue slightly above $5 billion.

No­vavax snags Ben Machielse for CMC and pro­motes a trio of staffers; Mar­ty Du­vall lands an­oth­er CEO post at On­copep­tides

Novavax has been making waves recently by securing a $384 million commitment from CEPI to cover R&D and manufacturing for its Covid-19 vaccine while also spending $167 million on a 150,000 square-foot facility. The Maryland biotech continues to shore up its leadership team as well, bringing in Ben Machielse as their EVP of CMC just a couple weeks after nabbing AstraZeneca vet Filip Dubrovsky as their new CMO. Machielse was president and CEO of Vtesse from 2014-17, and before that, he also spent more than 11 years at MedImmune and was EVP of operations for the back half of his tenure.

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Dan Gold, MEI Pharma CEO

De­vel­op­ment part­ners at MEI, Helsinn dump a high-risk PhI­II AML study af­ter con­clud­ing it would fail sur­vival goal

Four years after Switzerland’s Helsinn put $25 million of cash on the table for an upfront and near-term milestone to take MEI Pharma’s drug pracinostat into a long-running Phase III trial for acute myeloid leukemia, the partners are walking away from a clinical pileup.

The drug — an HDAC inhibitor — failed to pass muster during a futility analysis, as researchers concluded that pracinostat combined with azacitidine wasn’t going to outperform the control group in the pivotal.

Douglas Love, Annexon CEO (Annexon)

IPO bound? A Bay Area biotech grabs a mega-round on the road to a piv­otal neu­rode­gen­er­a­tion pro­gram

South San Francisco-based Annexon has added $100 million to its cash reserves, along with a new roster of marquee investors backing their play on the classical complement pathway involved in neurodegeneration. And that may well fit the profile for an IPO — though right now everything seems to be working on that score.

Eighteen months after Bain and their syndicate partners put up $75 million to fuel clinical work, Annexon is back at the trough. And this time they’re adding Redmile Group for the lead role, with supporting investments from these new arrivals: BlackRock, Deerfield Management Company, Eventide Asset Management, Farallon Capital Management, Janus Henderson Investors and Logos Capital.

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An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

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New stan­dard of care? FDA hands Pfiz­er, Mer­ck KGaA an OK for Baven­cio in blad­der can­cer

The breakthrough therapy designation Pfizer and Merck KGaA notched for Bavencio in bladder cancer has quickly paved way for a full approval.

The PD-L1 drug is now sanctioned as a first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma, applicable in cases where cancer hasn’t progressed after platinum-containing chemotherapy.

Petros Grivas, the principal investigator of the supporting Phase III JAVELIN Bladder 100, called the approval “one of the most significant advances in the treatment paradigm in this setting in 30 years.”