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.”

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

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UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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Gilead claims Tru­va­da patents in HHS’ com­plaint are in­valid

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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