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

Once fu­ri­ous over No­var­tis’ da­ta ma­nip­u­la­tion scan­dal, the FDA now says it’s noth­ing they need to take ac­tion on

Back in the BP era — Before Pandemic — the FDA ripped Novartis for its decision to keep the agency in the dark about manipulated data used in its application for Zolgensma while its marketing application for the gene therapy was under review.

Civil and criminal sanctions were being discussed, the agency noted in a rare broadside at one of the world’s largest pharma companies. Notable lawmakers cheered the angry regulators on, urging the FDA to make an example of Novartis, which fielded Zolgensma at $2.1 million — the current record for a one-off therapy.

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Covid-19 roundup: GSK, Am­gen tai­lor R&D work to fit the coro­n­avirus age; Doud­na's ge­nomics crew launch­es di­ag­nos­tic lab

You can add Amgen and GSK to the list of deep-pocket drug R&D players who are tailoring their pipeline work to fit a new age of coronavirus.

Following in the footsteps of a lineup of big players like Eli Lilly — which has suspended patient recruitment for drug studies — Amgen and GSK have opted to take a more tailored approach. Amgen is intent on circling the wagons around key studies that are already fully enrolled, and GSK has the red light on new studies while the pandemic plays out.

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In a stun­ning set­back, Amarin los­es big patent fight over Vas­cepa IP. And its high-fly­ing stock crash­es to earth

Amarin’s shares $AMRN were blitzed Monday evening, losing billions in value as reports spread that the company had lost its high-profile effort to keep its Vascepa patents protected from generic drugmakers.

Amarin had been fighting to keep key patents under lock and key — and away from generic rivals — for another 10 years, but District Court Judge Miranda Du in Las Vegas ruled against the biotech. She ruled that:
(A)ll the Asserted Claims are invalid as obvious under 35 U.S.C.§ 103. Thus, the Court finds in favor of Defendants on Plaintiff’s remaining infringementclaim, and in their favor on their counterclaims asserting the invalidity of the AssertedClaims under 35 U.S.C. § 103.

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Covid-19 roundup: J&J, BAR­DA set ear­ly 2021 fin­ish line for $1B vac­cine race; FDA al­lows emer­gency drug use, ahead of piv­otal da­ta

J&J has zeroed in on a Covid-19 vaccine candidate that it hopes to begin testing in humans by September this year — with the extraordinary goal of getting it ready for emergency use in early 2021. And together with BARDA, it’s committing $1 billion to make it happen.

That kind of accelerated timeline would fall on the fast side of NIAID director Anthony Fauci’s well-publicized prediction that it would be another 12 to 18 months before a vaccine can be available for public use. A Phase I trial of Moderna’s mRNA vaccine began two weeks ago, and both the biotech and fellow mRNA player CureVac have discussed similar, if not even faster, timelines for emergency use among healthcare workers.

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As­traZeneca says its block­buster Farx­i­ga proved to be a game-chang­er in CKD — wrap­ping PhI­II ear­ly

If the FDA can still hold up its end of the bargain, AstraZeneca is already on a short path to scooping up a cutting-edge win with a likely approval for their SGLT2 drug Farxiga in cutting the risk of heart failure. Now the pharma giant says it can point to solid evidence that the drug — initially restricted to diabetes — also works for chronic kidney disease, potentially adding a blockbuster indication for the franchise.

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It is 'kind of a proven tech­nol­o­gy': Hep B vac­cine mak­er joins glob­al hunt for coro­n­avirus vac­cine

Using lab-grown proteins that are engineered to mimic the architecture of viruses to induce an immune response, VBI Vaccines is joining the hunt for a coronavirus vaccine — harnessing technology that has initially been proved safe in early trials as a prophylactic for cytomegalovirus (CMV) infection.

Unlike the raft of the companies in the Covid-19 vaccine race — including Moderna, CureVac and J&J — VBI is taking a pan-coronavirus approach, by developing a vaccine that will encompass Covid-19, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS).

Can a pair of top AveX­is alum­ni steer a new gene ther­a­py up­start to R&D glo­ry? 3 VCs bet $60M on it

VCs love few things more than a proven executive team when it comes to launching a new company. And now a group of A-listers has turned to a pair of top execs out of AveXis to steer the latest gene therapy player into the clinic.

The biotech is Waltham, MA-based Affinia and the two execs are Sean Nolan and Rick Modi — the former CEO and CBO respectively of AveXis, the gene therapy pioneer that fetched $8.7 billion in a sale to Novartis. Nolan has now taken the chairman’s role at Affinia while Modi moves up to the CEO post at the company.

Un­de­terred by a pan­dem­ic, Gilde Health­care rais­es their largest fund yet

When Pieter van der Meer started raising the capital for Gilde Healthcare’s fifth fund in the waning months of 2019, he had his eyes on a different chain of events that could change the healthcare system and perhaps even play to his firm’s advantage: The US presidential election.

Since raising their third fund in 2011, the 34-year-old Dutch firm had focused on value-based care. They chose late-stage biotechs that came up with new devices and delivery systems for de-risked established compounds, and when they chose preclinical biotechs, they spoke with potential pharma partners, payers and regulators to ask where and at what prices the drug made sense. As the Democratic primary became a contest over how to lower healthcare costs, it looked like a strategy that could pay off.

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Gilead CEO Dan O'­Day of­fers a de­tailed ex­pla­na­tion on remde­sivir ac­cess — re­as­sur­ing an­a­lysts that Covid-19 da­ta are com­ing fast

After coming under heavy fire from consumer groups ready to pummel them for grabbing the FDA’s orphan status for remdesivir — reserved to encourage the development of rare disease therapies — Gilead CEO Daniel O’Day had some explaining to do about the company’s approach to providing access to this drug to patients suffering from Covid-19. And he set aside time over the weekend to patiently explain how they are making their potential pandemic drug available in a new program — one he feels can better be used to address a growing pack of infected patients desperately seeking remdesivir under compassionate use provisions.

In addition to trying to reassure patients that they will once again have an avenue to pursue access, O’Day also reassured some analysts who had been fretting that China’s quick comeback from the coronavirus outbreak could derail its ultra-fast schedule for testing the drug in patients. The data are still expected in a few weeks, he says in the letter, putting the readout in April.

O’Day emphasizes that Gilead intends to pursue a pricing approach that will make this drug widely available — if it proves effective and safe. But no one is quite sure just what the longterm value would be, given the work being done on a variety of vaccines that may be rolled out as early as this fall — at least to the most heavily threatened groups.

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