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.”

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Hal Barron, GSK via YouTube

What does $29B buy you in Big Phar­ma? In Glax­o­SmithK­line’s case, a whole lot of un­com­fort­able ques­tions about the pipeline

Talk about your bad timing.

A little over a week ago, GSK R&D chief Hal Barron marked his third anniversary at the research helm by taking a turn at the virtual podium during JP Morgan to make the case that he and his team had built a valuable late-stage pipeline capable of churning out more than 10 blockbusters in the next 5 years.

And then, just days later, one of the cancer drugs he bet big on as a top prospect — bintrafusp, partnered with Merck KGaA — failed its first pivotal test in non-small cell lung cancer.

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Janet Woodcock (AP Images)

End­points poll: Janet Wood­cock takes the (in­ter­im) helm at the FDA. And a large ma­jor­i­ty of our read­ers want her to stay there

It’s official: Janet Woodcock is now the acting chief of the FDA.

And — according to an Endpoints poll — most industry readers would like her to stay there, although a significant minority is strongly opposed.

To recap: Joe Biden is reportedly choosing between Woodcock and former deputy FDA commissioner Joshua Sharfstein as his nominee for the permanent position. Given their respective track records, the decision is set to determine the agency’s lodestar for years to come.

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What’s next for End­points — and how to sup­port our in­de­pen­dent bio­phar­ma news mis­sion

The firehose of biopharma news is gushing these days.

That’s why broader and deeper is the theme for 2021 at Endpoints. You can expect new coverage outside our core R&D focus, with deeper reporting in some key areas. When John Carroll and I launched Endpoints nearly five years ago, we were wading in waist-high waters. Now we’re a team of 25 full-time staffers (and growing) with plans to cover the flood of biopharma news, Endpoints-style.

Fast on Glax­o­SmithK­line's heels, Au­rinia wins OK to steer a sec­ond lu­pus nephri­tis drug straight to the mar­ket

GlaxoSmithKline’s Benlysta isn’t alone in the small circle of approved lupus nephritis drugs anymore.

Little Aurinia Pharmaceuticals has gotten the green light from the FDA to start marketing its first and only program, voclosporin, under the brand name Lupkynis — something CEO Peter Greenleaf says it’s been ready to do since December.

Regulators went right down to the wire on the decision, keeping the company and the entire salesforce it’s already assembled on its toes.

Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

It’s time for a new FDA commissioner to come on board, a rite of passage for Joe Biden’s administration that should help seal the new president’s rep on seeking out the experts to lead the government over the next 4 years.

As of now, the competition for the top job appears to have narrowed down to 2 people: The longtime CDER chief Janet Woodcock and Joshua Sharfstein, the former principal deputy at the FDA under Peggy Hamburg. Both were appointed by Barack Obama.

Eli Lil­ly's an­ti­body cuts risk of Covid-19 by up to 80% among the most vul­ner­a­ble — but will it have a place next to vac­cines?

Eli Lilly says bamlanivimab lowered the risk of contracting symptomatic Covid-19 in a first-of-its-kind trial involving nursing home residents and staff, paving the way for a new option to protect against the virus.

But how big of an impact it might have, and what role it will play, at a time vaccines are being rolled out to the exact population it is targeting still remains unclear.

Among 965 participants in the study — all of whom tested negative for the coronavirus at baseline — the number of symptomatic cases reported in the bamlanivimab arm was 57% lower than that in the placebo arm (odds ratio 0.43, p=0.00021). In addition to that primary endpoint, all secondary endpoints reached statistical significance.

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Hal Barron, GSK R&D chief (GSK via YouTube)

Glax­o­SmithK­line's $4B bis­pe­cif­ic can­cer drug al­liance with Mer­ck KGaA hit by big set­back with a PhI­II fail­ure on NSCLC

Close to 2 years ago, GSK’s R&D team eagerly agreed to pay up to $4 billion-plus to ally itself with Merck KGaA on a mid-stage bispecific called bintrafusp alfa, which intrigued them with the combination of a TGF-β trap with the anti-PD-L1 mechanism in one fusion protein.

But today the German pharma company says that their lead study on lung cancer was a bust, as independent monitors said there was no reason to believe that the experimental drug — targeting PD-L1/TGF-Beta — could beat Keytruda.

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Charlie Fuchs, Roche and Genentech global head of product development for oncology and hematology (Yale Cancer Center)

Yale can­cer spe­cial­ist Char­lie Fuchs tapped as new glob­al de­vel­op­ment chief for Roche/Genen­tech

Roche and their big sub Genentech have just recruited a top cancer specialist at Yale to head up global product development in oncology and hematology.

I just got word that the pharma giant, which leads one of the most active cancer research operations in the world, recruited Charlie Fuchs, director of the Yale Cancer Center and physician-in-chief of Smilow Cancer Hospital. He’ll join the global operation March 1 and will be based in South San Francisco, where Genentech is based.

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