Safe­ty fears spur FDA to pause check­point com­bo stud­ies by Bris­tol-My­ers, Cel­gene

Two months af­ter the FDA or­dered Mer­ck to slam the brakes on three Keytru­da com­bo stud­ies tar­get­ing mul­ti­ple myelo­ma, alarmed reg­u­la­tors have fol­lowed up by post­ing a stop sign on en­rolling any new pa­tients in Bris­tol-My­ers Squibb’s three ri­val stud­ies con­cen­trat­ing on the same dis­ease with the same com­bi­na­tion ap­proach­es. And hours lat­er Cel­gene $CELG added that it is be­ing forced to pause 5 com­bo stud­ies us­ing As­traZeneca’s Imfinzi while get­ting slammed with a full hold on one oth­er.

First to be of­fi­cial­ly frozen in place were Mer­ck’s KEYNOTE-183 and KEYNOTE-185 af­ter re­searchers spot­ted a high­er risk of death in the drug arms. Those mul­ti­ple myelo­ma tri­als matched Mer­ck’s block­buster ther­a­py with two drugs from Cel­gene: Po­m­a­lyst and its big drug Revlim­id. The FDA al­so or­dered pa­tients tak­en off of treat­ment in KEYNOTE-023 Co­hort 1, match­ing Keytru­da in com­bi­na­tion with lenalido­mide and dex­am­etha­sone in pa­tients who re­ceived pri­or an­ti-mul­ti­ple myelo­ma treat­ment with an im­munomod­u­la­to­ry (IMiD) treat­ment (lenalido­mide, po­ma­lido­mide or thalido­mide).

Wor­ried by ev­i­dence of safe­ty is­sues, the FDA fol­lowed up Wednes­day evening by or­der­ing a halt to en­roll­ment of new pa­tients in Bris­tol-My­ers’ stud­ies mar­ry­ing Op­di­vo with the same drugs: CA209602 (Check­Mate-602), CA209039 (Check­Mate-039) and CA204142 — al­so mul­ti­ple myelo­ma com­bo stud­ies.

At Cel­gene the dam­age is worse, with a full hold forc­ing re­searchers drop an ear­ly study look­ing at dur­val­um­ab in com­bi­na­tion with lenalido­mide with and with­out low-dose dex­am­etha­sone in mul­ti­ple myelo­ma pa­tients.

Com­bined, therse com­pa­nies have hun­dreds of com­bo stud­ies un­der­way, but reg­u­la­tors clear­ly be­lieve that there’s some oth­er threat to pa­tients in these par­tic­u­lar com­bi­na­tion stud­ies us­ing Cel­gene’s main­stay ther­a­pies. The FDA high­light­ed that con­cern just a week ago, care­ful­ly spelling out their rea­sons for sus­pend­ing the three Mer­ck stud­ies and point­ing out they were hunt­ing down and re­view­ing oth­er, sim­i­lar PD-(L)1 com­bos in the clin­ic.

Bris­tol-My­ers made for a nat­ur­al first stop in that process, with Cel­gene get­ting tagged at vir­tu­al­ly the same time.

The lat­est or­der from the FDA fol­lowed a stun­ning re­ver­sal for Cel­lec­tis, which was slammed with a clin­i­cal hold on Tues­day af­ter the first pa­tient treat­ed in its de­but off-the-shelf CAR-T study died, un­der­scor­ing the un­known risks that still con­front ad­vanced can­cer pa­tients sign­ing up for these ex­per­i­men­tal im­muno-on­col­o­gy tri­als.

Mer­ck and Bris­tol-My­ers are way out front with check­point in­hibitors Keytru­da and Op­di­vo as their PD-1 su­per­stars con­tin­ue to post jaw-drop­ping re­sults in can­cer. Clear­ly, though, as re­searchers con­tin­ue to test the bound­aries of what these new ther­a­pies can do un­ex­pect­ed safe­ty is­sues con­tin­ue to arise, rais­ing ques­tions of just how far de­vel­op­ers should take the drugs.

That same kind of safe­ty is­sue scut­tled Juno’s lead drug, which wound up killing three pa­tients last year af­ter the FDA pre­ma­ture­ly of­fered a green light to re­sume test­ing of its CAR-T af­ter a brief clin­i­cal hold. At this point, reg­u­la­tors ap­pear to be shift­ing their po­si­tion from an en­cour­ag­ing sig­nal to floor it, to a more cau­tious po­si­tion of study­ing safe­ty threats be­fore bar­rel­ing ahead.

For now, safe­ty is still a gray zone in im­muno-on­col­o­gy, as the da­ta con­tin­ues to pour in.

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Inside FDA HQ (File photo)

The FDA just ap­proved the third Duchenne MD drug. And reg­u­la­tors still don’t know if any of them work

Last year Sarepta hit center stage with the FDA’s controversial reversal of its CRL for the company’s second Duchenne muscular dystrophy drug — after the biotech was ambushed by agency insiders ready to reject a second pitch based on the same disease biomarker used for the first approval for eteplirsen, without actual data on the efficacy of the drug.

On Wednesday the FDA approved the third Duchenne MD drug, based on the same biomarker. And regulators were ready to act yet again despite the lack of efficacy data.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,700+ biopharma pros reading Endpoints daily — and it's free.

A lab technician works during research on coronavirus at Johnson & Johnson subsidiary Janssen Pharmaceutical in Beerse, Belgium, Wednesday, June 17, 2020. (Virginia Mayo/AP Images)

UP­DAT­ED: End­points News ranks all 28 play­ers in the Covid-19 vac­cine race. Here's how it stacks up to­day

(This piece was last updated on August 13. Endpoints News will continue to track the latest developments through the FDA’s marketing decisions.)

The 28 players now in or close to the clinical race to get a Covid-19 vaccine over the finish line are angling for a piece of a multibillion-dollar market. And being first — or among the leaders — will play a big role in determining just how big a piece.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,700+ biopharma pros reading Endpoints daily — and it's free.

Stéphane Bancel speaks to President Donald Trump at the White House meeting on March 2 (AP Images)

UP­DAT­ED: Mod­er­na of­fers steep dis­count in US sup­ply deal — but still takes the crown with close to $2.5B in vac­cine con­tracts

The US pre-order for Moderna’s Covid-19 vaccine is in.

Operation Warp Speed is reserving $1.525 billion for 100 million doses of Moderna’s Phase III mRNA candidate, rounding out to about $15 per dose — including $300 million in incentive payments for timely delivery. Given that Moderna has a two-dose regimen, it’s good for vaccinating 50 million people. The US government also has the option to purchase another 400 million doses for a total of $6.6 billion, or $16.5 per dose.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,700+ biopharma pros reading Endpoints daily — and it's free.

Cal­lid­i­tas bets up to $102M on a biotech buy­out, snag­ging a once-failed PBC drug

After spending years developing its oral formulation of the corticosteroid budesonide, Sweden’s Calliditas now has its sights set on the primary biliary cholangitis field.

The company will buy out France-based Genkyotex, and it’s willing to bet up to €87 million ($102 million) that Genkyotex’s failed Phase II drug, GKT831, will do better in late-stage trials.

Under the current agreement, Calliditas $CALT will initially pay €20.3 million in cash for 62.7% of Genkyotex (or €2.80 a piece for 7,236,515 shares) in early October, then circle back for the rest of Genkyotex’s shares under the same terms. If nothing changes, the whole buyout will cost Calliditas €32.3 million, plus up to  €55 million in contingent rights.

Giovanni Caforio, Bristol Myers Squibb CEO (Christopher Goodney/Bloomberg via Getty Images)

UP­DAT­ED: Bris­tol My­ers Squibb com­mits $300 mil­lion to com­bat racial dis­par­i­ties, but de­clines to re­lease own de­mo­graph­ic da­ta

After the police killing of George Floyd, a flurry of pharma and biotech companies, executives and investors jumped out to make statements, either expressing support for Black Lives Matter and the protests or condemning systemic racism.

Now, a Big Pharma company is publicly putting some teeth behind those statements. This morning, Bristol Myers Squibb announced they would spend $300 million on a broad effort to reduce racial health disparities, and diversify both their clinical trials and their own executive team and workforce.

Martin Shkreli (AP Images)

Mar­tin Shkre­li's in­fa­mous Dara­prim falls off top 20 most ex­pen­sive drugs list

Martin Shkreli incited a national uproar five years ago when he raised the price of Daraprim by a factor of 56 essentially overnight from $13.50 to $750 per pill. Now that the “Pharma Bro’s” high-priced project has received a generic, it no longer places among the most expensive drugs in the world.

GoodRx is back with the latest update of the top 20 most expensive drugs and Daraprim’s exclusion marks the biggest change. The drug had previously ranked seventh on the list’s last iteration, which came in February before the world went into quarantine. Another of Shkreli’s former companies, Retrophin, saw its Chenodal drug place in the top 10 again.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,700+ biopharma pros reading Endpoints daily — and it's free.

Qi­a­gen in­vestors spurn Ther­mo Fish­er’s takeover of­fer, de­rail­ing a $12B+ deal

Thermo Fisher Scientific had announced an $11.5 billion takeover of Dutch diagnostics company Qiagen back in March, but the deal apparently did not sit well with Qiagen investors.

After getting hammered by critics who contended that Qiagen $QGEN was worth a lot more than what Thermo Fisher wanted to spend, investors turned thumbs down on the offer — derailing the buyout even after Thermo Fisher increased its offer to $12.6 billion in July. Qiagen’s share price has been boosted considerably by Covid-19 as demand for its testing kits surged.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 87,700+ biopharma pros reading Endpoints daily — and it's free.

Xuefeng Yu in Hong Kong, 2019 (Imaginechina via AP Images)

CanSi­no reaps $748M wind­fall from Shang­hai IPO — as it warns Covid-19 vac­cine won't be a huge mon­ey mak­er

CanSino began the year with a clear goal to secure a secondary listing on Shanghai’s STAR market. Then something more urgent came along: As a rising vaccine developer on a mission to bring global standard immunizations to China, it heeded the call to make a vaccine to protect against a virus that would paralyze the whole world.

Xuefeng Yu and his team managed to keep doing both.

More than a month after CanSino’s Covid-19 vaccine candidate is authorized for military use in China, the Hong Kong-listed company has made a roaring debut in Shanghai. It fetched $748 million (RMB$5.2 billion) by floating 24.8 million shares, and soared 88% on its first trading day.