Tech glitch­es over­shad­ow FDA on­col­o­gy ad­comm as a sol­id ma­jor­i­ty of ad­vis­ers vote to keep Roche's Tecen­triq in mTNBC

Kick­ing off three days of re­ex­am­in­ing an­ti-PD(L)-1 ac­cel­er­at­ed ap­provals, the FDA’s On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee start­ed slow­ly on Tues­day. Af­ter a more than hour-long tech­ni­cal de­lay, 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.

But tech­ni­cal glitch­es at the hear­ing kept dis­cus­sions among the com­mit­tee’s can­cer ex­perts to on­ly a few ques­tions for Genen­tech, and the au­dio cut out be­fore the com­mit­tee mem­bers of­fered any of their typ­i­cal ex­pla­na­tions af­ter their votes.

Triple-neg­a­tive breast can­cer (TNBC) is no­to­ri­ous­ly dif­fi­cult to treat, rep­re­sent­ing 10-20% of breast can­cers, with a me­di­an sur­vival af­ter di­ag­no­sis of just 12 to 18 months and a 5-year sur­vival rate of 15%, ex­plained Char­lie Fuchs, a Yale can­cer spe­cial­ist who joined Roche in Jan­u­ary.

The good: With lim­it­ed oth­er treat­ment op­tions, Tecen­triq ini­tial­ly won its ac­cel­er­at­ed ap­proval in com­bi­na­tion with nab-pa­cli­tax­el for adult pa­tients with mTNBC whose tu­mors ex­press PD-L1 in March 2019 based on a me­di­an pro­gres­sion-free sur­vival (PFS) of 7.4 months, which com­pared with 4.8 months for those on place­bo in com­bo with nab-pa­cli­tax­el.

The bad: The con­fir­ma­to­ry tri­al did not pan out, and even showed a wor­ri­some sign as the place­bo out­per­formed the treat­ment com­bo in terms of over­all sur­vival.

Laleh Amiri-Ko­rdestani, di­vi­sion di­rec­tor at the Of­fice of On­co­log­ic Dis­eases, pre­sent­ed for the FDA on Tues­day and al­so not­ed that the over­all sur­vival re­sults in the ini­tial tri­al (on which the ac­cel­er­at­ed ap­proval is based) may be due to chance alone, and that the ben­e­fit seen in the first tri­al was not cor­rob­o­rat­ed in a sim­i­lar pop­u­la­tion in the con­fir­ma­to­ry tri­al.

The ug­ly: She al­so called the over­all sur­vival re­sults in the con­fir­ma­to­ry tri­al “con­cern­ing.” Those re­sults led to an alert from the agency and a la­bel up­date in De­cem­ber be­cause of the “pos­si­bil­i­ty of detri­ment” in over­all sur­vival.

Pre­sent­ing for Genen­tech, Steve Chui, glob­al de­vel­op­ment lead in on­col­o­gy, spelled out both the ben­e­fit from the ini­tial tri­al and how the con­fir­ma­to­ry tri­al did not show a PFS ben­e­fit. He al­so ex­plained how the re­sults from the con­fir­ma­to­ry tri­al showed 101 of those on place­bo and pa­cli­tax­el had a me­di­an of 28.3 months of over­all sur­vival, com­pared with 22.1 months for 191 of those on ate­zolizum­ab and pa­cli­tax­el.

Look­ing to the fu­ture, Chui point­ed to con­ver­sa­tions from De­cem­ber with FDA on oth­er pos­si­ble con­fir­ma­to­ry tri­als, in­clud­ing one that would use a dif­fer­ent type of chemo along with Tecen­triq in about 570 mTNBC pa­tients, which is ex­pect­ed to see re­sults in 2023. Oth­er tri­als pro­posed won’t read out un­til 2023 or 2024.

The FDA said in its brief­ing doc­u­ments that “it is not yet clear which of these tri­als are suf­fi­cient­ly de­signed to ad­e­quate­ly con­firm ben­e­fit,” and ad­comm pan­elists ques­tioned why one of the tri­als would use dif­fer­ent chemother­a­pies if it’s a con­fir­ma­to­ry tri­al for Tecen­triq and nab-pa­cli­tax­el. But the ma­jor­i­ty of mem­bers still vot­ed to keep the in­di­ca­tion un­der an ac­cel­er­at­ed ap­proval.

Pri­or to the dis­cus­sion of ate­zolizum­ab, Ju­lia Beaver, chief of med­ical on­col­o­gy at FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, opened the meet­ing by ex­plain­ing how ac­cel­er­at­ed ap­provals on­ly need to be “rea­son­ably like­ly to pre­dict clin­i­cal ben­e­fit,” and that of the 151 ac­cel­er­at­ed ap­provals for on­col­o­gy drugs, 35 have been for PD-(L)1 an­ti­bod­ies, in­clud­ing the three un­der scruti­ny this week, and a to­tal of 10 have been with­drawn.

Those with­drawals have come as the treat­ment land­scape may have changed or be­cause fol­low-up tri­als have failed to con­firm ben­e­fits.

Mov­ing Out of the Clin­ic with Dig­i­tal Tools: Mo­bile Spirom­e­try Dur­ing COVID-19 & Be­yond

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.

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Sanofi, Glax­o­SmithK­line jump back in­to the PhI­II race for a Covid vac­cine — as the win­ners con­gre­gate be­hind the fin­ish line

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.

The Supreme Court on Monday denied Novartis subsidiary Sandoz’s petition to review a Federal Circuit’s July 2020 decision concerning its biosimilar Erelzi (etanercept-szzs), which FDA approved in 2016 as a biosimilar to Amgen’s Enbrel (etanercept). Samsung’s Enbrel biosimilar Eticovo also won approval in 2019 and remains sidelined.

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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.

In­cyte keeps rolling on top­i­cal cream for JAK in­hibitor, pass­ing two PhI­II tests in vi­tili­go

As Incyte prepares to potentially hit the market with a topical formulation of its cash cow ruxolitinib in atopic dermatitis, the Wilmington, DE-based company is beefing up its data package for another indication: vitiligo.

Incyte released Phase III results from two of its clinical vitiligo programs Monday morning, saying both studies met their primary endpoints of patients achieving at least 75% improvement from baseline in repigmentation of the face. The data will likely lead Incyte to ask for approval in both the US and Europe for those older than 12 before the end of the year.

Tim Mayleben (L) and Sheldon Koenig (Esperion)

On the heels of a sting­ing Q1 set­back, Es­pe­ri­on's long­time cham­pi­on is ex­it­ing the helm and turn­ing the wheel over to a mar­ket­ing pro

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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Days ahead of Am­gen split, Cy­to­ki­net­ics reads out post-hoc da­ta sug­gest­ing heart drug works bet­ter in sick­er pa­tients — but can the CEO win over skep­tics?

While Cytokinetics’ heart drug technically met its primary endpoint back in November, it missed a key secondary endpoint — reduction in cardiovascular death — which eventually cost the company two partnerships. Now the team is back with data suggesting the drug works better in sicker patients, and it’s planning a trip to the FDA.

In a post-hoc analysis, which can be a very difficult sale at the FDA, Cytokinetics separated patients from the Phase III GALACTIC-HF study into four quartiles based on ejection fraction, a measurement of how well the left ventricle pumps blood with each heartbeat. Patients in the lower two quartiles — those with an EF of 22% or lower, and between 29% to 32% — saw a 15% and 17% relative risk reduction of heart failure events and cardiovascular death combined, Cytokinetics reported at ACC. No difference was seen in the upper two quartiles.

Neil Desai, Aadi Bioscience CEO (Specialised Therapeutics via YouTube)

Patrick Soon-Sh­iong's for­mer chief sci­en­tist takes can­cer com­pa­ny pub­lic in $155M re­verse merg­er

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SPACs have become the preferred fast track for public markets over the past year, but apparently there’s still room for a good, old-fashioned reverse merger.

Cancer-focused Aadi Bioscience announced Monday that they would merge with the struggling public biotech Aerpio Pharmaceuticals. To go along with the merger, Aadi raised $155 million from private investors to commercialize their lead drug, Fyarro, which is now sitting before the FDA. Acuta Capital Partners and KVP Capital led the round.

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