FDA slaps down No­var­tis' block­buster pitch for canakinum­ab — so what went wrong?

In a ma­jor set­back, No­var­tis used its quar­ter­ly earn­ings re­port to flag an FDA slap­down on their ap­pli­ca­tion to mar­ket canakinum­ab for car­dio risk re­duc­tion.

Vas Narasimhan

Tout­ed as a block­buster in­di­ca­tion, the phar­ma gi­ant steered this drug through a big late-stage de­vel­op­ment pro­gram, even pulling out da­ta on a large sub­group of pa­tients that could ben­e­fit from the drug. The then de­vel­op­ment chief Vas Narasimhan was pro­mot­ed to CEO in part on the suc­cess he had with this drug — on­ly to get hit with a com­plete re­sponse let­ter.

A spokesper­son for the com­pa­ny of­fered an ex­pla­na­tion for what went wrong at the FDA:

Based on the cor­re­spon­dence from the FDA, the CAN­TOS da­ta would not sup­port la­bel­ing for the use of canakinum­ab as a tar­get­ed ther­a­py for those pa­tients with car­dio­vas­cu­lar dis­ease who achieved a re­duc­tion of hsCRP be­low the 2 mg/L tar­get. At this time, we are eval­u­at­ing the feed­back pro­vid­ed and plans fur­ther dis­cus­sions with the FDA.

That said, we are con­tin­u­ing to study canakinum­ab to treat non-small cell lung can­cer in sev­er­al Phase 3 stud­ies, with the first tri­al com­ple­tion ex­pect­ed in 2022.

The re­jec­tion is a par­tic­u­lar­ly bit­ter pill for No­var­tis to swal­low now, af­ter tout­ing the drug fol­low­ing the col­lapse of its ef­fort to get their oth­er car­dio drug sere­lax­in ap­proved.

Tim An­der­son

The an­ti-in­flam­ma­to­ry drug, sold as Ilaris for a niche mar­ket, earned $380 mil­lion last year. And con­sid­er­ing da­ta on an added risk of in­fec­tion as well as some ex­perts fret­ting about the some­what fuzzy clar­i­ty of the ben­e­fit ini­tial­ly on dis­play, Tim An­der­son pegged the peak sales at a con­sen­sus of $800 mil­lion, while not­ing that patent pro­tec­tion should run out in on­ly 7 years.

Oth­er an­a­lysts were much more up­beat, with Bank Von­to­bel of­fer­ing good odds of $2 bil­lion in peak sales — mon­ey No­var­tis needs to spur rev­enue growth.

Jef­feries’ Michael Yee not­ed:

Al­though over­all the drug showed a 15% CV ben­e­fit on the pri­ma­ry end­point, based on pri­or com­men­tary, it is like­ly NVS was seek­ing to in­clude the pre-spec­i­fied sub-group of pts who are able to get to >1.7-2.0mg of hsCRP re­duc­tion which led to much larg­er 25-27% CV ben­e­fits. NVS may feel this is the pop­u­la­tion that has sig­nif­i­cant ben­e­fit and would dri­ve suf­fi­cient com­mer­cial op­por­tu­ni­ty rather than the more mod­est 15% CV ben­e­fit in the over­all en­rolled pop­u­la­tion. While doc com­men­tary has sug­gest­ed that NVS would tar­get per­haps a seg­ment (ie 30-40%) of over­all high CV risk mar­ket (pts who had pri­or MI too) and not re­al­ly com­pete much for the pts tak­ing AMGN PC­SK9, it would be keen to watch this as a 25-27% ben­e­fit would be com­pelling for pts in the mar­ket…As a re­minder, ES­PR has al­so shown a sig­nif­i­cant 40% re­duc­tion in hsCRP as well in its stud­ies which may help add con­fi­dence to over­all treat­ment ef­fect in their CVOT study (we look to up­com­ing im­por­tant Phase III safe­ty da­ta com­ing H2 Oc­to­ber…if clean and no ma­jor im­bal­ances, this could bode well for ES­PR).

The treat­ment is de­signed to in­hib­it IL-1ß, a key cy­tokine, for a pro­longed pe­ri­od, tamp­ing down on in­flam­ma­tion to low­er risk to pa­tients.

Re­searchers al­so pulled out pos­i­tive sub­group da­ta on gout from the CAN­TOS study, which tracked more than 10,000 pa­tients for more than 6 years — one of the biggest stud­ies in the phar­ma gi­ant’s his­to­ry.

There is a side ben­e­fit to this drug that No­var­tis has been puz­zling out. The drug pro­duced a re­duc­tion in lung can­cer mor­tal­i­ty of 77%, un­der­scor­ing their the­o­ry that in­hibit­ing IL-1ß could pro­duce promis­ing da­ta in on­col­o­gy.

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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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.

Bio­haven adds near­ly $1B in Nurtec deals with Roy­al­ty Phar­ma, Sixth Street

Biohaven just added nearly $1 billion to their balance sheet.

On Friday morning, the neuroscience biotech announced a pair of creative agreements with Royalty Pharma and the investment firm Sixth Street to bolster the commercial launch of their new migraine drug, Nurtec. Biohaven will sell a sliver of its royalties on Nurtec and 3% of the royalties on their experimental migraine drug zavegepant to Royalty Pharma as part of a larger agreeement that will pay $450 million. At the same time, the company announced they took out a $500 million loan from Sixth Street.

Ab­b­Vie set­tles in­sur­ance fraud suit, agrees to tweak nurse am­bas­sador pro­gram; CStone aims for NSCLC OK with pos­i­tive PhI­II da­ta

AbbVie has resolved a California lawsuit alleging insurance fraud in the promotion of its cash cow Humira, paying $24 million to settle things with the state’s insurance regulator.

The settlement comes almost four years after a whistleblower first reported AbbVie’s practice of deploying registered nurses to visit patients at home or call them by phone to ensure that Humira prescriptions are filled. AbbVie was also charged with providing illegal kickbacks to doctors in an attempt to encourage them to prescribe Humira for a range of anti-inflammatory diseases.

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.

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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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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