FDA ap­proves ex-No­var­tis drug for Cush­ing’s dis­ease

Two months af­ter win­ning Eu­ro­pean ap­proval, a one-time No­var­tis or­phan drug for Cush­ing’s dis­ease has been OK’d by the FDA.

Is­tur­isaknown chem­i­cal­ly as os­ilo­dro­stat, has been ap­proved as a twice-dai­ly pill for those who have not un­der­gone the pi­tu­itary gland surgery of­ten used to treat Cush­ing’s dis­ease, or for those whose symp­toms per­sist af­ter the op­er­a­tion. No­var­tis sold the com­pound along­side two oth­er en­docrine drugs to the Ital­ian phar­ma Recor­dati last Ju­ly for $390 mil­lion, plus Is­tur­isa mile­stones.

A mod­er­ate deal rel­a­tive to No­var­tis’s of­ten high-rolling ta­ble, the terms re­flect­ed the re­al but lim­it­ed mar­ket po­ten­tial for that slice of the com­pa­ny’s en­docrine port­fo­lio. Gen­er­al­ly caused by a non-can­cer­ous tu­mor on the pi­tu­itary gland that caus­es the body to re­lease too much cor­ti­sol, Cush­ing’s af­fects a lit­tle over a mil­lion Amer­i­cans each year. It can cause a range of health prob­lems, in­clud­ing high blood pres­sure, type 2 di­a­betes and change in ap­pear­ance. In ad­di­tion to Is­tur­isa, the deal al­so in­clud­ed al­ready ap­proved Cush­ing’s dis­ease drugs Sig­ni­for and Sig­ni­for LAR.

Most pa­tients are treat­ed with surgery, but not all pa­tients are el­i­gi­ble for surgery, and surgery doesn’t al­ways work. For those pa­tients, doc­tors of­ten pre­scribe drugs that block hu­man growth hor­mone, such as Sig­ni­for, or a drug that blocks an en­zyme in­volved in cor­ti­sol pro­duc­tion, such as metyrapone.

Is­tur­isa works by tar­get­ing a new en­zyme. It blocks 11-be­ta-hy­drox­y­lase, one of the last en­zymes in a chain the body us­es to make cor­ti­sol.

In a Phase III tri­al of 137 adults last year, the drug brought about half of all pa­tients down to nor­mal cor­ti­sol pro­duc­tion dur­ing the 24-week, sin­gle-arm, open-la­bel phase. The 71 pa­tients who tol­er­at­ed and re­spond­ed to the drug were then en­rolled in an 8-week dou­ble-blind phase, test­ing it against place­bo. At the end of the phase, 86% on the drug arm had cor­ti­sol with­in nor­mal ranges, com­pared with 30% of place­bo pa­tients.

Still, the lim­it­ed tri­al left key ques­tions unan­swered, most no­tably how long it will work. Af­ter the En­docrine So­ci­ety meet­ing where the tri­al re­sults were an­nounced, ses­sion co-mod­er­a­tor and as­so­ciate di­rec­tor of the Pi­tu­itary Cen­ter at the Uni­ver­si­ty of Penn­syl­va­nia Ju­lia Khar­lip told Med­scape, “It is like­ly go­ing to work.”

But she cau­tioned that the drug it re­places — metyrapone, which is tak­en four times a day and blocks a dif­fer­ent en­zyme — is known to even­tu­al­ly be­come in­ef­fec­tive as the tu­mor es­sen­tial­ly over­rides the en­zyme block­ade.

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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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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George Yancopoulos (Regeneron)

UP­DAT­ED: 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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Vas Narasimhan, Novartis CEO (Patrick Straub/​EPA-EFE/​Shutterstock)

No­var­tis pays $678M for kick­back scheme as Vas Narasimhan tries to dis­tance phar­ma gi­ant from shady be­hav­ior

Novartis has reached another large settlement to resolve misconduct allegations, agreeing to pay more than $678 million to settle claims that it had spent hundreds of millions of dollars on lavish dinners, so-called speaking fees and expensive alcohol “that were nothing more than bribes” to get doctors to prescribe Novartis medications.

The top-shelf alcohol and lavish meals included a $3,250 per person night at Nobu in Dallas, a $672-per person dinner at Washington DC’s Smith & Wollensky and a $314 per person meal at Sushi Roku in Pasadena, according to the Justice Department complaint. There were at least 7 trips to Hooters and fishing trips in Alaska and off the Florida coast. Each of these events were supposed to be “speaker programs” where doctors educated other doctors on a drug, but the DOJ alleged many were “bogus” wine-and-dine events where the drug was barely mentioned, if at all.  (“Nobody presented slides on the fishing trips,” the complaint says.)

Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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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.”

On a roll, Mer­ck blazes through a new seg­ment of the bio­mark­er trail

Merck has notched an approval for using Keytruda to treat a biomarker-based subset of first-line colorectal cancer patients with unresectable or metastatic tumors, as the pharma giant continues to find new niches for its blockbuster PD-1 star.

The OK is significant in a number of ways. Not only does it build on an accelerated approval for all tumors characterized as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); it also marks the first single treatment for colorectal cancer that doesn’t contain chemotherapy.

Look­ing for 'ex­ter­nal in­no­va­tion,' Boehringer In­gel­heim re­serves $500M+ for new Shang­hai hub

Now that Boehringer Ingelheim’s bet on contract manufacturing in China has paid off, the German drugmaker is anteing up more to get into the research game.

Boehringer has set aside $507.9 million (€451 million) for a new External Innovation Hub to be built in Shanghai over five years. The site will become one of its “strategic pillars” as the team strives to get 71 approvals — either for new products or indications — by 2030, said Felix Gutsche, president and CEO of Boehringer Ingelheim China.