ODAC votes to keep Keytru­da and Tecen­triq ac­cel­er­at­ed ap­provals in blad­der can­cer

The FDA’s On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee is con­tin­u­ing to find it dif­fi­cult to say no to can­cer pa­tients, es­pe­cial­ly as blad­der can­cer pa­tients af­fect­ed by Wednes­day’s votes have few oth­er treat­ment op­tions.

Pe­ter Kang

On Wednes­day morn­ing, ODAC vot­ed 5-3 in fa­vor of keep­ing Keytru­da’s (pem­brolizum­ab) ac­cel­er­at­ed ap­proval alive as a first line blad­der can­cer treat­ment for those who are cis­platin-in­el­i­gi­ble and car­bo­platin-in­el­i­gi­ble, even af­ter a Mer­ck con­fir­ma­to­ry tri­al failed.

And on Wednes­day af­ter­noon, ODAC vot­ed 10-1 in fa­vor of keep­ing Genen­tech’s Tecen­triq (ate­zolizum­ab) as a first-line treat­ment of cis­platin-in­el­i­gi­ble pa­tients with ad­vanced/metasta­t­ic blad­der can­cer pend­ing fi­nal over­all sur­vival re­sults from a con­fir­ma­to­ry tri­al, known as IMvig­or130.

Among those vot­ing in fa­vor of Keytru­da — Mer­ck’s mega-block­buster drug, with 19 full ap­provals, in­clud­ing a full ap­proval as a sec­ond-line blad­der can­cer treat­ment, and 10 ac­cel­er­at­ed ap­provals — sev­er­al physi­cians point­ed to the lack of oth­er treat­ments for cer­tain pa­tients.

While the con­fir­ma­to­ry tri­al did not show a ben­e­fit for Keytru­da as a first-line treat­ment, much of the dis­cus­sion cen­tered on these sub­groups of pa­tients who might have no treat­ment op­tions with­out Keytru­da.

“Ac­cess to pem­brolizum­ab re­mains im­por­tant for these pa­tients, and FDA ap­proval should be main­tained un­til ad­di­tion­al con­fir­ma­to­ry da­ta are avail­able,” Pe­ter Kang, VP of clin­i­cal re­search at Mer­ck, told the com­mit­tee.

Laleh Amiri-Ko­rdestani

As far as how Mer­ck might still con­firm ben­e­fit in this in­di­ca­tion, Kang point­ed to one study that would look at Keytru­da in com­bi­na­tion with Ei­sai’s Lenvi­ma, com­pared with Keytru­da and place­bo. That tri­al is ex­pect­ed to be com­plet­ed in Oc­to­ber 2023. But the FDA said it would be chal­leng­ing to use this tri­al as it does not iso­late the ef­fect of Keytru­da. Two oth­er po­ten­tial con­fir­ma­to­ry tri­als from Mer­ck may al­so be used to con­firm its ben­e­fit, and are ex­pect­ed to fin­ish in mid-2025 and 2027.

Lay­ing out the case for FDA, Laleh Amiri-Ko­rdestani, di­vi­sion di­rec­tor in FDA’s Of­fice of On­co­log­ic Dis­eases, not­ed that the clin­i­cal tri­al ev­i­dence does not sup­port con­tin­ued ap­proval for Keytru­da in this set­ting.

Ronac Mam­tani

She al­so ex­plained how the treat­ment land­scape has changed, as last June, FDA ap­proved EMD Serono’s Baven­cio (avelum­ab) for those with blad­der can­cer who have not pro­gressed with first-line plat­inum-con­tain­ing chemother­a­py.

But Ronac Mam­tani, blad­der can­cer doc­tor at the Uni­ver­si­ty of Penn­syl­va­nia, took to the pub­lic fo­rum at the meet­ing and stressed what oth­er pan­elists had been hint­ing at — that re­tain­ing this in­di­ca­tion could be crit­i­cal for some pa­tients who are cis­platin-in­el­i­gi­ble.

For the af­ter­noon ses­sion, pan­elists were over­whelm­ing­ly in fa­vor of wait­ing for the over­all sur­vival re­sults from a con­fir­ma­to­ry tri­al to read out for Tecen­triq be­fore de­cid­ing on whether to pull the blad­der can­cer in­di­ca­tion.

Mo­hum­mad Sid­diqui, di­rec­tor of uro­log­ic on­col­o­gy at the Uni­ver­si­ty of Mary­land Med­ical Cen­ter, vot­ed to keep this ac­cel­er­at­ed ap­proval for Tecen­triq and said the in­ter­im analy­sis looks promis­ing and the FDA should wait for the fi­nal analy­sis from IMvig­or130. And Rick Paz­dur, FDA’s top on­col­o­gy head, sweet­ened the of­fer for Roche/Genetech, not­ing that if the com­pa­ny hits on the over­all sur­vival in the tri­al, they’ll be able to con­vert the Tecen­triq monother­a­py ac­cel­er­at­ed ap­proval to full ap­proval and the com­pa­ny will win a new in­di­ca­tion for Tecen­triq in com­bi­na­tion with chemo.

Mo­hum­mad Sid­diqui

Philip Hoff­man, chair of ODAC, was the on­ly com­mit­tee mem­ber to vote against keep­ing this Tecen­triq ac­cel­er­at­ed ap­proval, and he said he was con­cerned by with­draw­al of the Roche/Genen­tech drug in the sec­ond line set­ting as the pri­ma­ry end­point of over­all sur­vival was not met.

The votes on Wednes­day fol­lowed Tues­day’s meet­ing, in which com­mit­tee mem­bers vot­ed 7-2 to keep alive the ac­cel­er­at­ed ap­proval for Genen­tech’s Tecen­triq (ate­zolizum­ab) plus Abrax­ane (nab-pa­cli­tax­el) in metasta­t­ic triple neg­a­tive breast can­cer (mTNBC) while ad­di­tion­al con­fir­ma­to­ry tri­als are on­go­ing.

Three more ac­cel­er­at­ed ap­provals (in­clud­ing two for Keytru­da and one for Bris­tol My­ers Squibb’s Op­di­vo) are set for votes on Thurs­day. While the FDA does not have to fol­low the ad­vice of ODAC, it gen­er­al­ly does.

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An important technology in assessing lung function, spirometry offers crucial data for the diagnosis and monitoring of pulmonary system diseases, as well as the ongoing measurement of treatment efficacy. But trends in the healthcare industry and new challenges introduced by the COVID-19 pandemic are causing professionals in clinical practice and research to reevaluate spirometry’s deployment methods and best practices.

Paul Hudson (Getty Images)

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Sanofi got out early in the race to develop a vaccine using more of a traditional approach, then derailed late last year as their candidate failed to work in older people. Now, after likely missing the bus for the bulk of the world’s affluent nations, they’re back from that embarrassing collapse with a second attempt using GSK’s adjuvant that may get them back on track — with a potential Q4 launch that the rest of the world will be paying close attention to.

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SCO­TUS de­clines to re­view En­brel biosim­i­lar case, tee­ing up 30+ years of ex­clu­siv­i­ty and $20B more for Am­gen’s block­buster

As the House Oversight Committee is set to grill AbbVie CEO Richard Gonzalez on Tuesday over tactics to block competition for its best-selling drug of all time, another decision on Capitol Hill on Monday opened the door for billions more in Amgen profits over the next eight years.

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How to man­u­fac­ture Covid-19 vac­cines with­out the help of J&J, Pfiz­er or Mod­er­na? Bi­ol­yse sees the dif­fi­cul­ties up close

When Biolyse, an Ontario-based manufacturer of sterile injectables, forged a deal with Bolivia last week to manufacture up to 50 million J&J Covid-19 vaccine doses, the agreement kicked off what will prove to be a test case for how difficult the system of compulsory licenses is to navigate.

The first problem: When Biolyse asked J&J, via a March letter, to license its Covid-19 vaccine, manufacture it in Canada and pay 5% royalties on shipments to needy, low-income countries, J&J rejected the offer, refusing to negotiate. J&J also did not respond to a request for comment.

No­var­tis' En­tresto takes its 2nd fail­ure of the week­end at ACC, show­ing no ben­e­fit in most dire heart fail­ure pa­tients

Novartis’ Entresto started the ACC weekend off rough with a trial flop in heart attack patients, slowing the drug’s push into earlier patients. Now, an NIH-sponsored study is casting doubt on Entresto’s use in the most severe heart failure patients, another black mark on the increasingly controversial drug’s record.

Entresto, a combination of sacubitril and valsartan, could not beat out valsartan alone in an outcomes head-to-head for severe heart failure patients with a reduced ejection fraction (HFrEF), according to data presented Monday at the virtual American College of Cardiology meeting.

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Just days after getting stung by criticism from a badly disappointed group of analysts, there’s a big change happening today at the helm of Esperion $ESPR.

Longtime CEO Tim Mayleben, who championed the company for 9 years from early clinical through a lengthy late-stage drive to successfully get their cholesterol drug approved for a significant niche of patients in the US, is out of the C suite, effective immediately. Sheldon Koenig — hired at the end of 2020 with a resume replete with Big Pharma CV sales experience —  is stepping into his place, promising to right a badly listing commercial ship that’s been battered by market forces.

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Matt Gline (L) and Vivek Ramaswamy

In­sid­er ac­count of Roivan­t's SPAC deal — and that $7.3B val­u­a­tion — re­veals a few se­crets as Matt Gline po­si­tions the com­pa­ny as the new ‘Big Phar­ma’

It was Oct. 7, 2020, and Matt Gline wasn’t wasting any time.

The CEO of Roivant had word that KKR vet Jim Momtazee’s SPAC had priced late the night before, triggering a green light for anyone interested in pursuing a big check for future operations and riding the financial instrument to Nasdaq. So he wrote a quick email congratulating Momtazee, whom he knew, for the launch.

Oh, and maybe Momtazee would like to schedule something with Gline and his executive chairman, Roivant founder Vivek Ramaswamy, to chat about Roivant and its business?

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