MyoKar­dia steps clos­er to the launch of a ground­break­ing heart tri­al af­ter find­ing its low-dose start­ing point

MyoKar­dia $MYOK is one step clos­er to launch­ing a piv­otal tri­al for its ge­net­i­cal­ly tar­get­ed lead heart drug.

In the sec­ond part of their two-step Phase II tri­al, the South San Fran­cis­co-based biotech says it land­ed pos­i­tive da­ta for a slate of end­points with their low-dose ap­proach to ob­struc­tive hy­per­trophic car­diomy­opa­thy. That’s en­cour­ag­ing them to drop off the top and bot­tom dos­es from the full scale up and fo­cus on the 5 mg, 10 mg and 15 mg steps in the range.

But there’s a catch. The low-dose 2 mg-step-up-to-5 mg arm did hit goals for most end­points, but at that lev­el their drug mava­camten al­so failed to achieve a sta­tis­ti­cal­ly sig­nif­i­cant in­crease in peak VO2 (ex­er­cise ca­pac­i­ty as mea­sured by an in­crease in oxy­gen con­sump­tion), which the com­pa­ny out­lined ear­li­er as the in­tend­ed pri­ma­ry end­point for their piv­otal study, dubbed EX­PLOR­ER-HCM.

In fact, that was the on­ly end­point that didn’t achieve sta­tis­ti­cal sig­nif­i­cance with a p val­ue of 0.121.

“That is the one mea­sure that did not hit sta­tis­ti­cal sig­nif­i­cance, but that is not sur­pris­ing,” MyoKar­dia CEO Tas­sos Gi­anakakos tells me. The re­searchers want­ed to find the bot­tom of an ef­fec­tive range, and they have plen­ty of proof-of-con­cept da­ta from about 20 pa­tients in both co­horts to con­vince them they have good rea­son to be­lieve it will work when they move to a place­bo-con­trolled reg­is­tra­tion study with a dose that starts out at 5 mg and can rise to 15 mg. They add that you al­so shouldn’t just dis­miss the pos­i­tive trend that they saw at the low dose.

MyoKar­dia is break­ing new ground in this study in many ways, and not just with the first new drug to be stud­ied for this con­di­tion. It’s a small com­pa­ny tak­ing on heart dis­ease, a field dom­i­nat­ed by gi­ants like No­var­tis, which have the means to mount huge, long-run­ning stud­ies that cost a for­tune. But the biotech isn’t tak­ing on mass car­dio con­di­tions — it’s look­ing to break up its re­search pro­gram in­to tight­ly con­tained buck­ets of ge­net­i­cal­ly de­fined pa­tient groups. Its lead drug tar­gets a mu­ta­tion in heart pro­teins which forces the heart to squeeze more, thick­en­ing heart mus­cles and cre­at­ing a cas­cade of ef­fects and symp­toms that can lead to afib­ril­la­tion and death.

So they’ve been look­ing for the Goldilocks for­mu­la­tion that can achieve the right serum con­cen­tra­tions of the drug — per­mit­ting physi­cians to step up from a low dose that may well prove ef­fec­tive for a large chunk of pa­tients be­fore go­ing on to find the right lev­el for the rest, while not over­step­ping their in­tend­ed im­pact on the heart.

MyoKar­dia — which has seen its hot stock more than triple in val­ue since its first read­out from their mid-stage study — had out­lined a time­line for launch­ing the reg­is­tra­tion study be­fore the end of 2017. Now dos­ing is ex­pect­ed to get start­ed in the sec­ond quar­ter.

That’s lat­er than what they had en­vi­sioned last sum­mer, con­cedes the CEO. But the ex­ec­u­tive team wants to take time for two sit-downs with the FDA, fol­low­ing up to make sure reg­u­la­tors are com­fort­able with the da­ta they have, the de­sign of the piv­otal tri­al and the piv­otal goals they’ll be us­ing, stick­ing with peak VO2 for the pri­ma­ry.

MyoKar­dia is hold­ing back from pro­vid­ing a time­line on the read­out from the EX­PLOR­ER study. They want to get the FDA’s sign off and start dos­ing pa­tients, judg­ing how fast they can re­cruit the pa­tients they need. Then they’ll tell the world what to ex­pect.

If they’re right, MyoKar­dia could well be on the way to pi­o­neer­ing some­thing rad­i­cal­ly new — and that’s no easy task.

Im­age: MyoKar­dia CEO Tas­sos Gi­anakakos. MYOKAR­DIA

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.

UP­DAT­ED: Roche fields first ap­proval for Ro­z­lytrek in the run-up to a show­down with Bay­er, Pfiz­er

While it’s wait­ing to hear back from FDA reg­u­la­tors, Roche is be­gin­ning the vic­to­ry lap for en­trec­tinib in Japan.

Roche is giv­ing Bay­er a run for their mon­ey with this tu­mor-ag­nos­tic drug, which tar­gets NTRK gene fu­sions. Now dubbed Ro­z­lytrek, it’s sanc­tioned to treat adult and pe­di­atric pa­tients in Japan with neu­rotroph­ic ty­ro­sine re­cep­tor ki­nase fu­sion-pos­i­tive, ad­vanced re­cur­rent sol­id tu­mors.

In­vestors fret as VBI's hep B vac­cine fails key sec­ondary PhI­II study goal

Sobered by mount­ing costs, Dy­navax $DVAX last month made the de­ci­sion to fo­cus all its re­sources on its 2017-ap­proved he­pati­tis B vac­cine Hep­lisav-B, which ri­vals and su­per­sedes the ef­fi­ca­cy and con­ve­nience pro­file of GSK’s $GSK es­tab­lished En­ger­ix-B. The Cal­i­for­nia-based com­pa­ny will be on the look­out for an­oth­er com­peti­tor — VBI Vac­cines, which on Mon­day un­veiled late-stage da­ta on its hep B vac­cine: Sci-B-Vac.

Image: Shutterstock

Gene ther­a­py R&D deals turn red hot as Big Phar­ma steps up to play

This September will mark the 20th anniversary of the death of Jesse Gelsinger, a young man suffering from X-linked genetic disease of the liver. He was killed in a gene therapy study conducted by Penn’s James Wilson, and the entire field endured a lengthy deep freeze as the field grappled with the safety issues inherent in the work.

Some thought gene therapy R&D would never survive. But it did. And this year marked a landmark approval for Zolgensma, a new gene therapy for spinal muscular atrophy Novartis priced at $2.1 million.

“Gene therapy is the hottest item on the block now. But there was a time when we first got into this trial, where there wasn’t a person in the world who believed that gene therapy would work. We have to remember that,” noted gene therapy investigator Jerry Mendell told SMA News Today.

We’re still right on the pioneering frontier when it comes to getting approvals for gene therapies and launching marketing campaigns with the European green light for bluebird's leading program last Friday underscoring the nascent nature of the field. But gene therapy R&D is booming, and has been for several years now.

The rapid growth of gene therapy clinical development is well known, but we decided to put some numbers on it, to quantify what’s going on. DealForma chief Chris Dokomajilar took a lot over the past 10 years, as the number of deals, R&D partnerships and buyouts steadily gained steam, spiking last year and on track to maintain the surge in 2019.

The upfronts and totals for the dollars on deals so far in 2019 is already close to the 2018 mark, underscoring a new phase of negotiations as the major players step up to gain a piece of the late-stage and commercial action.

Once again, we’re looking at an “overnight” biotech success story, decades in the making.

At some point, that may start to brake the numbers we’re seeing. But for now, as rivals line up to compete for frontline prominence across a range of diseases, the arrows are all pointed north.

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Albert Bourla appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

UP­DAT­ED: Pfiz­er CEO Al­bert Bourla is back in the M&A game, but why is he pay­ing $11.4B for Ar­ray?

Pfiz­er $PFE has cut short its time on the side­lines of bio­phar­ma M&A.

Mon­day morn­ing the phar­ma gi­ant un­veiled an $11.4 bil­lion deal to ac­quire Ar­ray Bio­Phar­ma, beef­ing up its on­col­o­gy work and adding a new re­search hub in Boul­der, Col­orado to its glob­al op­er­a­tions.

At $48 a share, Ar­ray $AR­RY in­vestors will be get­ting a 62% pre­mi­um off the Fri­day close of $29.59.

Pfiz­er, which has strug­gled to gain all the up­side promised in past buy­outs like Medi­va­tion, high­light­ed the ac­qui­si­tion of 2 ap­proved drugs in the deal — Braftovi (en­co­rafenib) and Mek­tovi (binime­tinib).

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Step­ping on Roche's toes, Mer­ck cuts in­to SCLC niche with third-line Keytru­da OK

In the in­creas­ing­ly crowd­ed check­point race, small cell lung can­cer has been a rare area where Roche, a sec­ond run­ner-up, has a lead over the en­trenched lead­ers Mer­ck and Bris­tol-My­ers Squibb. But Mer­ck is fi­nal­ly mak­ing some head­way in that di­rec­tion with the lat­est ap­proval for its PD-1 star.

The lat­est green light en­dors­es Keytru­da in the third-line treat­ment of metasta­t­ic SCLC, where it would be giv­en to pa­tients whose dis­ease ei­ther don’t re­spond to or re­lapse af­ter chemother­a­py, which would have fol­lowed at least one pri­or line of ther­a­py.

Af­ter watch­ing its share price soar on a Bloomberg re­port and heat­ed ru­mors, Bio­haven stock takes a bil­lion-dol­lar bath

Back in April, Biohaven Pharmaceutical became one hot biotech stock $BHVN based on a report in Bloomberg that some “potential bidders” had been kicking the tires at the biotech, which has a lead drug for migraines. Then the rumor mill really started to smoke when execs canceled a presentation at an investor conference a little more than a week ago.

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