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.

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.

Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

Endpoints News

Basic subscription required

Unlock this story instantly and join 55,200+ biopharma pros reading Endpoints daily — and it's free.