FDA ex­perts turn thumbs down on J&J’s trou­bled rheuma­toid arthri­tis drug sirukum­ab

Faced with a big red flag reg­u­la­tors raised on safe­ty, a pan­el of out­side ex­perts turned thumbs down on ap­prov­ing J&J’s sirukum­ab for rheuma­toid arthri­tis, con­clud­ing that there wasn’t a clear enough un­der­stand­ing of the drug’s safe­ty pro­file to jus­ti­fy the risk of putting it on the mar­ket.

The vote was 12 to 1 against the drug, say­ing that the safe­ty pro­file did not jus­ti­fy an OK. That was the key is­sue, and they fol­lowed up by the same num­bers in a for­mal vote against an ap­proval.

Dan Solomon

Har­vard Med’s Dan Solomon sum­ma­rized the thoughts of the ma­jor­i­ty, say­ing he vot­ed no “based on not feel­ing con­fi­dence about the safe­ty of this drug.”

Sev­er­al of the ex­perts shook their heads over what they agreed were trou­bling but mys­te­ri­ous ev­i­dence that there was an im­bal­ance in deaths among the tri­al pa­tients tak­ing the drug. While J&J in­sist­ed that the over­all ev­i­dence in­di­cat­ed that the risk/ben­e­fit ra­tion jus­ti­fied an ap­proval, some of the ex­perts al­so won­dered why they would ap­prove an­oth­er IL drug with trou­bling safe­ty sig­nals while two oth­er such drugs were al­ready on the mar­ket that didn’t have the same safe­ty prob­lems.

The group, though, were sat­is­fied that re­searchers had pro­vid­ed am­ple ef­fi­ca­cy da­ta to demon­strate the drug’s val­ue.

The FDA is not ob­lig­at­ed to fol­low the pan­el’s lead, but gen­er­al­ly does. Even if it should be ap­proved against all odds, the ex­perts on the pan­el made it clear that a for­mu­la­ry com­mit­tee would have no trou­ble ei­ther re­fus­ing re­im­burse­ment or re­strict­ing it as an ab­solute last re­sort, se­vere­ly lim­it­ing any mar­ket po­ten­tial.

J&J, though, has lit­tle choice now but to play this one out.

New­man Yeild­ing, Janssen

“While the com­mit­tee vot­ed unan­i­mous­ly in sup­port of the ef­fi­ca­cy da­ta, there was un­cer­tain­ty re­gard­ing the safe­ty pro­file. As a re­sult, the com­mit­tee did not sup­port ap­proval for the pro­posed in­di­ca­tion. We are dis­ap­point­ed and dis­agree with the group’s in­ter­pre­ta­tion of the sirukum­ab ben­e­fit-to-risk pro­file,” said New­man Yeild­ing, head of im­munol­o­gy de­vel­op­ment, Janssen Re­search & De­vel­op­ment, in a state­ment. “We re­main con­fi­dent in the da­ta ac­cu­mu­lat­ed to date sup­port­ing sirukum­ab in the treat­ment of mod­er­ate­ly to se­vere­ly ac­tive rheuma­toid arthri­tis. We look to con­tin­ue dis­cus­sions with the FDA in their re­view of the ap­pli­ca­tion as we be­lieve sirukum­ab rep­re­sents an im­por­tant ther­a­peu­tic op­tion for pa­tients with rheuma­toid arthri­tis.”

J&J was fac­ing an up­hill fight on this quest. The FDA has al­ready re­in­forced just how sen­si­tive it is on safe­ty is­sues when it re­ject­ed Eli Lil­ly’s baric­i­tinib and de­mand­ed an­oth­er study to prove its safe­ty. Then Glax­o­SmithK­line dumped its rights in the drug just days ago, leav­ing J&J to go on alone.

In an in­ter­nal re­view at the FDA, reg­u­la­tors con­clud­ed:

Wide con­fi­dence in­ter­vals around treat­ment com­par­isons for se­ri­ous rare events such as death, ma­lig­nan­cy, and MACE in­di­cate that the im­bal­ances could be due to chance but al­so that rel­a­tive­ly large in­creas­es in risks on sirukum­ab can­not be ruled out based on the da­ta alone. Such im­bal­ances raise con­cern re­gard­ing these im­por­tant safe­ty risks. Ad­di­tion­al safe­ty sig­nals re­lat­ed to events of GI per­fo­ra­tion and hy­per­sen­si­tiv­i­ty were al­so ob­served.

J&J may well face whether it wants to buck­le down and do a ma­jor safe­ty study ahead of a for­mal de­ci­sion, or give it up and move on. It won’t be an easy de­ci­sion.

Here comes the oral GLP-1 drug for di­a­betes — but No­vo Nordisk is­n't dis­clos­ing Ry­bel­sus price just yet

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Rybelsus will be the first GLP-1 pill to enter the type 2 diabetes market — a compelling offering that analysts have pegged as a blockbuster drug with sales estimates ranging from $2 billion to $5 billion.

Ozempic, the once-weekly injectable formulation of semaglutide, brought in around $552 million (DKK 3.75 billion) in the first half of 2019.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

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A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

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Oxitec biologist releases genetically modified mosquitoes in Piracicaba, Brazil in 2016 [credit: Getty Images]

In­trex­on unit push­es back against claims its GM mos­qui­toes are mak­ing dis­ease-friend­ly mu­tants

When the hysteria of Zika transmission sprang into the American zeitgeist a few years ago, UK-based Oxitec was already field-testing its male Aedes aegypti mosquito, crafted to possess a gene engineered to obliterate its progeny long before maturation.

But when a group of independent scientists evaluated the impact of the release of these genetically-modified mosquitoes in a trial conducted by Oxitec in Brazil between 2013 and 2015, they found that some of the offspring had managed to survive — prompting them to speculate what impact the survivors could have on disease transmission and/or insecticide resistance.

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Pur­due threat­ens to walk away from set­tle­ment, asks to pay em­ploy­ees mil­lions in bonus­es

There are two updates on the lawsuit against Purdue Pharma over its role in fueling the opioid epidemic, as the Sackler family threatens to walk away from their pledge to pay out $3 billion if a bankruptcy judge does not stop outstanding state lawsuits against them. At the same time, the company has asked permission to pay millions in bonuses to select employees.

Purdue filed for chapter 11 bankruptcy this week as part of its signed resolution to over 2,000 lawsuits. The deal would see the Sackler family that owns Purdue give $3 billion from their personal wealth and the company turned into a trust committed to curbing and reversing overdoses.

Aerial view of Genentech's campus in South San Francisco [Credit: Getty]

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The sign is still there, a quaint reminder of whitewashed concrete not 5 miles from Genentech’s sprawling, chrome-and-glass campus: South Francisco The Industrial City. 

The city keeps the old sign, first erected in 1923, as a tourist site and a kind of civic memento to the days it packed meat, milled lumber and burned enough steel to earn the moniker “Smokestack of the Peninsula.” But the real indication of where you are and how much has changed both in San Francisco and in the global economy since a couple researchers and investors rented out an empty warehouse 40 years ago comes in a far smaller blue sign, resembling a Rotary Club post, off the highway: South San Francisco, The Birthplace of Biotech.

While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While Novartis painstakingly works to mop up the stench of the data manipulation scandal associated with its expensive gene therapy for spinal muscular atrophy (SMA) Zolgensma— rival Biogen is attempting to expand the use of its SMA therapy, Spinraza. 

The US drugmaker $BIIB secured US approval for Spinraza for use in the often fatal genetic disease in 2016. The approval covered a broad range of patients with infantile-onset (most likely to develop Type 1) SMA. 

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Eye­ing big ther­a­peu­tic push, Gink­go bags $290M to build a cell pro­gram­ming em­pire

Ginkgo Bioworks is on a roll. Days after publicizing a plan to nurture new startups via partnerships with accelerators Y Combinator and Petri, the Boston biotech says it has raised another $290 million for its cell programming platform to reach further and wider.

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UP­DAT­ED: Speak­er Nan­cy Pelosi to un­veil bill for fed­er­al­ly ne­go­ti­at­ed drug prices

After months of buzz from both sides of the aisle, Speaker Nancy Pelosi will today introduce her plan to allow the federal government to negotiate prices for 250 prescription drugs, setting up a showdown with a pharmaceutical industry working overtime to prevent it.

The need to limit drug prices is a rare point of agreement between President Trump and Democrats, although the president has yet to comment on the proposal and will likely face pressure to back a more conservative option or no bill at all. Republican Senator Chuck Grassley is reportedly lobbying his fellow party members on a more modest proposal he negotiated with Democratic Senator Ron Wyden in July.