Mer­ck halts en­roll­ment on two PhI­II Keytru­da com­bo stud­ies as out­side mon­i­tors flag a wor­ry­ing rate of deaths

Mer­ck $MRK has had to hit the brakes on en­rolling new pa­tients for two of its late-stage com­bo stud­ies in­volv­ing its block­buster check­point Keytru­da af­ter the mon­i­tor­ing com­mit­tee raised a red flag on an im­bal­ance of deaths in the stud­ies in­volv­ing mul­ti­ple myelo­ma.

Treat­ment in the two tri­als will con­tin­ue, says Mer­ck, as they try to eval­u­ate why there were more deaths in the Keytru­da arms of KEYNOTE-183 and KEYNOTE-185. The tri­als in­volve com­bi­na­tions with Cel­gene’s Po­m­a­lyst as well as its flag­ship drug Revlim­id in a field Cel­gene dom­i­nates in.

Mer­ck shares slid 1.3% as in­vestors got their first whiff of bad news about Keytru­da in some time.

Roger Perl­mut­ter, Mer­ck

Keytru­da isn’t just Mer­ck’s biggest drug in the pipeline. It rep­re­sents a pipeline of its own for R&D chief Roger Perl­mut­ter, with dozens of com­bi­na­tion stud­ies un­der­way as the phar­ma gi­ant hur­ries to ex­pand its use. These check­points, in­clud­ing Bris­tol-My­ers Squibb’s Op­di­vo, have had a ma­jor im­pact for some pa­tients, un­leash­ing an im­mune sys­tem at­tack on can­cer cells in a va­ri­ety of tu­mors. But their grow­ing use has come with a num­ber of nasty sur­pris­es over what works and what doesn’t, as Roche found when its PD-L1 su­per­star Tecen­triq failed a re­cent Phase III.

Right now, though, there’s no ex­act ex­pla­na­tion for what trig­gered the im­bal­ance in deaths among a very sick group of pa­tients who had al­ready failed ear­li­er ther­a­pies.

Ex­plains Mer­ck:

KEYNOTE-183 is a Phase 3 study com­par­ing po­ma­lido­mide and low-dose dex­am­etha­sone with KEYTRU­DA to po­ma­lido­mide (Po­m­a­lyst) and low-dose dex­am­etha­sone alone in pa­tients with re­frac­to­ry or re­lapsed and re­frac­to­ry mul­ti­ple myelo­ma (rrMM) who have un­der­gone at least 2 lines of pri­or treat­ment. KEYNOTE-185 is a Phase 3 study com­par­ing lenalido­mide (Revlim­id) and low-dose dex­am­etha­sone with KEYTRU­DA to lenalido­mide and low-dose dex­am­etha­sone alone in pa­tients with new­ly di­ag­nosed and treat­ment-naïve mul­ti­ple myelo­ma who are in­el­i­gi­ble for au­tol­o­gous stem cell trans­plant (Au­to-SCT).

Cred­it Su­isse an­a­lysts were ready to shrug off the jit­ters. In a note, they re­port­ed:

We spoke with MRK, and they con­firmed that this is not a clin­i­cal hold; en­rolled pa­tients are con­tin­u­ing with their treat­ment reg­i­mens. How­ev­er, they were not able to pro­vide ad­di­tion­al col­or re­gard­ing how many pa­tients have died, or whether the im­bal­ance was seen in both stud­ies, or just one study with both halt­ed for pre­cau­tion­ary mea­sures. We have seen da­ta from the Po­m­a­lyst com­bo be­fore in a Phase I study that was pre­sent­ed at ASH in 2015, and there were no signs of an ob­vi­ous tox­i­c­i­ty with the com­bi­na­tion that were of con­cern to doc­tors.

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Jeff Albers, Blueprint CEO

Di­ag­nos­tic champ Roche buys its way in­to the RET ti­tle fight with Eli Lil­ly, pay­ing $775M in cash to Blue­print

When Roche spelled out its original $1 billion deal — $45 million of that upfront — with Blueprint to discover targeted therapies against immunokinases, the biotech partner’s RET program was still preclinical. Four years later, pralsetinib is on the cusp of potential approval and the Swiss pharma giant is putting in much more to get in on the commercial game.

Roche gains rights to co-develop and co-commercialize the drug, with sole marketing responsibility for places outside the US and China (where CStone has staked its claim).

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A neoanti­gen pi­o­neer says its tech is work­ing great. So what wrecked the share price?

Gritstone Oncology was one of the original neoantigen upstarts, raising cash and planning to disrupt the immuno-oncology field with a bold new approach to fighting cancer with a new brand of vaccines.

On Monday, the crew in charge ran out a full display of what they’ve been seeing in a Phase I study. And everything seems to be working perfectly with one big exception: It didn’t significantly shrink tumors, let alone eradicate them.

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Janet Woodcock, CDER chief (AP Images)

More Warp Speed con­tracts com­ing, vac­cine pro­duc­tion to be­gin in 4-6 weeks — of­fi­cials

Operation Warp Speed has already handed out 4 of what they once said would be 3-5 major contracts to develop Covid-19 vaccines, but administration officials indicated Monday that more would be on their way.

“The slate is not closed,”  a senior HHS official said on a call with reporters. “We’ve invested in four … but the slate is not closed.”

At the same time, the official indicated that Warp Speed would continue to focus on three technologies: mRNA, viral vectors and protein subunits. That leaves the door open for a wide range of platforms, notably including both of Merck’s vaccine candidates — one of which has already received BARDA funding — and one of Sanofi’s candidates. It appears to preclude, though, the potential for Inovio and Vaxart, among certain other small developers that have hyped their ties to the Trump administration, to be included.

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For two months in late winter and early spring, Anthony Fauci and President Trump stood in uneasy co-existence at White House briefings — an unlikely truce between an infectious disease official who had helped combat AIDS and Ebola and a president who repeatedly denied the danger of a virus that would go on to kill 100,000 Americans, repeatedly rejected masks and certain social distancing efforts, and promoted a drug with little scientific basis.

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Stéphane Bancel, Moderna CEO (Andrew Harnik/AP Images)

A top an­a­lyst turns the spot­light on Mod­er­na, fu­el­ing a fast-and-fu­ri­ous Street race over the fu­ture of mR­NA

Bioregnum Opinion Column by John Carroll

Four months ago, one of the favorite talking points on the biopharma social media wave length was whether Moderna shares $MRNA were priced right or were wildly inflated.

After all, said the naysayers, the company had never actually pushed a treatment to an approval. Did messenger RNA really work, coding cells to make a drug or a vaccine? And how about all that chatter about how ‘secretive’ they are, or were?

Now, as CEO Stéphane Bancel and the top execs push the company to the forefront of a frantic race to develop the first vaccine to fight against the reignited wildfire spread of Covid-19, all those questions have been magnified — along with the stock price.

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Covid-19 roundup: Af­ter de­lays, gov­ern­ment dis­putes, Mod­er­na sets PhI­II launch; Clin­i­cal tri­als have re­turned — for now

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Albert Bourla, AP

Covid-19 roundup: CanSi­no eyes more over­seas PhI­II sites as Cana­da tri­al re­port­ed­ly stalls; In­di­an drug­mak­er surges on 30-per­son da­ta

Having leveraged connections in Canada for a planned Phase III trial of its Covid-19 vaccine, CanSino is venturing out to a few more others as it plots a global late-stage program.

“We are contacting Russia, Brazil, Chile and Saudi Arabia, and it’s still in discussion,” Dongxu Qiu, executive director and co-founder of CanSino, said at a conference in Suzhou, China, per Reuters.

The trial is likely to start “pretty soon,” he added, with plans to recruit 40,000 participants total.

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