KalVis­ta's di­a­bet­ic mac­u­lar ede­ma da­ta falls short — will Mer­ck walk away?

Mer­ck’s 2017 bet on KalVista Phar­ma­ceu­ti­cals may have soured, af­ter the UK/US-based biotech’s lead drug failed a mid-stage study in pa­tients with di­a­bet­ic mac­u­lar ede­ma (DME).

Two dos­es of the in­trav­it­re­al in­jec­tion, KVD001, were test­ed against a place­bo in a 129-pa­tient tri­al. Pa­tients who con­tin­ued to ex­pe­ri­ence sig­nif­i­cant in­flam­ma­tion and di­min­ished vi­su­al acu­ity, de­spite an­ti-VEGF ther­a­py, were re­cruit­ed to the tri­al. Typ­i­cal­ly pa­tients with DME — the most fre­quent cause of vi­sion loss re­lat­ed to di­a­betes — are treat­ed with an­ti-VEGF ther­a­pies such as Re­gen­eron’s flag­ship Eylea or Roche’s Avastin and Lu­cen­tis.

An­drew Crock­ett

KVD001 is en­gi­neered to in­hib­it an en­zyme called plas­ma kallikrein and was de­vel­oped on the ba­sis of re­search that in­di­cat­ed en­hanced lev­els of the pro­tein are present in the vit­re­ous flu­id in the eyes of peo­ple with DME. Pre­clin­i­cal da­ta sug­gest plas­ma kallikrein in­hi­bi­tion is key to a de­cline in reti­nal thick­en­ing and bet­ter pro­cess­ing of vi­su­al sig­nals, ac­cord­ing to KalVista.

How­ev­er, nei­ther dose of KVD001 met the main goal of the Phase II study, which was to in­duce a sta­tis­ti­cal­ly sig­nif­i­cant change in best-cor­rect­ed vi­su­al acu­ity (BC­VA) at 16 weeks ver­sus place­bo (6 μg = +2.6 let­ters or 3 μg = +1.5 let­ters; p=0.465). No sig­nif­i­cant dif­fer­ences from place­bo emerged on any of the sec­ondary end­points in­clud­ing cen­tral sub­field thick­ness or the di­a­bet­ic retinopa­thy sever­i­ty scale, the com­pa­ny said, adding that the drug was gen­er­al­ly safe and well-tol­er­at­ed.

The com­pa­ny’s stock tum­bled $KALV more than 17% to $11.88 in pre­mar­ket trad­ing.

Still, KalVista high­light­ed some sil­ver lin­ings from sub­group analy­ses that chief An­drew Crock­ett said could jus­ti­fy fur­ther study of the drug in the DME pop­u­la­tion.

Pa­tients giv­en the high­er dose of KVD001 saw a slow­er re­duc­tion in vi­sion loss at 32.5% ver­sus place­bo at 54.5%, al­though the dif­fer­ence was not deemed sta­tis­ti­cal­ly sig­nif­i­cant (p=0.042). Af­ter ex­clud­ing pa­tients with the most se­vere lev­els of vi­sion loss, the re­main­ing 70% of the to­tal pa­tient pop­u­la­tion showed a dif­fer­ence in BC­VA com­pared to place­bo of 4.9 let­ters at the 6 μg dose, al­though again the dif­fer­ence was not sta­tis­ti­cal­ly sig­nif­i­cant (p=0.056).

“From a look at the da­ta and var­i­ous sec­ondary/sub­group analy­ses it does ap­pear that there were some trends to­wards ben­e­fit in the study, but we doubt it will gain cred­it from in­vestors in the ab­sence of an­oth­er cor­rob­o­rat­ing tri­al,” Stifel’s Paul Mat­teis wrote in a note, in­di­cat­ing that the fail­ure is not a huge sur­prise.

In 2017, Mer­ck paid $8.50 a share for a 10% stake in KalVista and a fur­ther $37 mil­lion up­front for an op­tion to buy KVD001.

“We think in­vestors buy­ing the stock to­day should large­ly as­sume that this pro­gram won’t move for­ward. If Mer­ck pass­es on the as­set it’s pos­si­ble KALV could look for an­oth­er part­ner, but again, fig­ur­ing out the next steps here, if there are any, may take time,” Mat­teis said.

End­points News has con­tact­ed Mer­ck for com­ment.

KalVista has an­oth­er plas­ma kallikrein in­hibitor in its ar­se­nal, the oral ther­a­py KVD900, un­der de­vel­op­ment for hered­i­tary an­gioede­ma (HAE). Da­ta from a Phase II tri­al are ex­pect­ed next year.

“(W)e see no readthrough on­to KVD900: in HAE plas­ma kallikrein is a val­i­dat­ed tar­get, and in DME it is an in­ter­est­ing tar­get that, un­like in HAE, has nev­er be­fore been the foun­da­tion for ap­proved/ef­fec­tive drugs,” Mat­teis not­ed. “In turn, we con­tin­ue to gain op­ti­mism in the prospects for KVD900, based on the suc­cess of oth­er med­ica­tions in the space, and our work…based on the tri­an­gu­la­tion of PK/PD da­ta which we think sup­port ‘900 as an oral res­cue med with po­ten­tial “in­jec­tion-like” ef­fi­ca­cy.”

Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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Ryan Watts, Denali CEO

Bio­gen hands De­nali $1B-plus in cash, $1B-plus in mile­stones to part­ner on late-stage Parkin­son’s drug

Biogen is handing over more than a billion dollars cash to partner with the up-and-coming neurosciences crew at Denali on a new therapy for Parkinson’s. And the big biotech is ready to pile on more than a billion dollars more in milestones — if the alliance is a success.

For Biogen $BIIB, the move on Denali’s small molecule inhibitors of LRRK2 puts them in line to collaborate on a late-stage program for DNL151, which is scheduled to start next year.

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Moncef Slaoui, Getty Images

When will it end? Big Phar­ma's top vac­cine ex­pert at OWS of­fers a speedy time­line for a Covid-19 vac­cine — ei­ther be­fore or right af­ter the elec­tion

Moncef Slaoui hasn’t started making plans for his summer vacation next year. But he offers high odds that all Americans will be able to do that in the not too distant future.

In an interview with a pair of sympathetic podcasters at the conservative American Enterprise Institute, Slaoui provides an education to listeners on how any drug or vaccine can be sped through trials. And he leaves the door wide open to the notion that the leading vaccine developers can demonstrate efficacy and safety in a compelling fashion as early as October — or as late as the end of this year.

Per­cep­tive fields SPAC #3 as an­oth­er group of biotechs scoops up $364M in lat­est Nas­daq romp

There’s no sign that the windfall of cash dropping biotech’s way on Wall Street is abating. Three more biopharmas priced IPOs on Thursday and Friday morning, riding a historic boom with a $364 million payoff.

London-based biotech Freeline Therapeutics took home the lion’s share of the cash with $159 million after pricing 8,823,529 shares at $18 a pop. Checkmate Pharmaceuticals, of Cambridge, MA, raised $75 million with an offer of 5 million shares at $15 — right at the midpoint of its range. And Arya Sciences Acquisition Corp III, the third in a series from Perceptive, priced 13,000,000 shares at $10 per share.

Covid-19 roundup: Gates Foun­da­tion pours $150M in­to In­dia’s Serum In­sti­tute; Pfiz­er teams with Gilead on remde­sivir

By CEO and scion Adar Poonawalla’s estimation, the Serum Institute in India has already poured hundreds of millions of dollars into scaling up the unproven Covid-19 vaccine being developed by AstraZeneca and Oxford for use in low and middle income countries. It’s meant taking on a risk that other companies, including AstraZeneca, have mitigated with huge amounts of government funding.

Now, for the first time, Poonawalla is getting some outside help. The Gates Foundation has agreed to pay the institute $150 million to supply 100 million vaccines to India and other emerging economies next year, Reuters reported. That includes both the vaccine being developed by AstraZeneca and the one being developed by Novavax. Those vaccines will be available in 92 countries and be priced at $3 per dose.

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In sur­pris­ing set­back, com­bo of Roche’s Tecen­triq and chemo fails to help pa­tients with triple-neg­a­tive breast can­cer

Roche broke ground last year when they secured the first FDA approval for a checkpoint therapy in triple-negative breast cancer, a notoriously difficult-to-treat indication that has been passed over by the wave of targeted therapies.

Now, though, doctors are puzzling over why a combination of drugs meant to make that therapy more potent instead appeared to make it less effective.

Roche said Thursday that in a Phase III trial, combining their PD-1/L1 checkpoint therapy Tecentriq with the chemotherapy paclitaxel, did not significantly improve progression-free survival for patients with locally advanced or metastatic triple-negative breast cancer over giving those patients chemotherapy alone. In fact, patients on the Tecentriq-chemo arm had lower overall survival than patients on chemo, although the drugmaker cautioned that the trial was not powered for that endpoint and the data were immature.

Douglas Fambrough, Dicerna CEO (Boehringer Ingelheim via YouTube)

Roche-backed Dicer­na push­es in­to the pack rac­ing to­ward the block­buster hep B goal line, armed with PhI da­ta

Dicerna has lined up a set of proof-of-concept data from a small cohort of hepatitis B patients in a match-up against some heavyweight rivals which got out in front of this race. And right in the front row you’ll find a team from Roche, which paid $200 million in cash and offered another $1.5 billion in milestones to partner with Dicerna $DRNA on their RNAi program for hep B.

Right now it’s looking competitive, with lots of big challenges ahead.

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Lund­beck sounds taps on an­oth­er CNS drug, re­treat­ing from a mine field still oc­cu­pied by a Mer­ck team

Lundbeck has snipped another clinical-stage branch of its CNS research, dumping a schizophrenia program after determining that their therapy would have no positive influence on the disease.

Designed originally as a 240-patient study, researchers set out in early 2019 to see if a homegrown drug dubbed Lu AF11167 could make it through a proof-of-concept study. The drug is a PDE10Ai inhibitor, targeting an enzyme which it said at the time offered a new pathway to retuning the body’s neurotransmitter dopamine. The big idea was that by hitting their target, the drug would modulate “dopamine D1 and D2 receptor-mediated intraneuronal signaling without binding to these receptors,” influencing negative symptoms of schizophrenia.

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Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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