Back­lash: Har­vard ex­perts fret over the fall­out from FDA’s OK for Sarep­ta’s con­tro­ver­sial Duchenne drug

Two of Har­vard’s top FDA pol­i­cy ex­perts, Aaron Kessel­heim and Jer­ry Avorn, have ex­pressed some deep con­cerns about the agency’s ap­proval of eteplirsen, OK’d to be sold as Ex­ondys 51 for $300,000-plus a year, and the im­pli­ca­tions for fur­ther show­downs in the near fu­ture as more de­vel­op­ers look to test the bound­aries on the agency’s stan­dards.

Writ­ing on­line in the Jour­nal of the Amer­i­can Med­ical As­so­ci­a­tion, the two re­viewed the cam­paign used to back eteplirsen, win­ning an OK with scant ev­i­dence of suc­cess in pro­duc­ing dy­s­trophin — con­trary to what Sarep­ta had claimed — a prob­lem­at­ic re­liance on his­tor­i­cal com­par­isons, and the unan­i­mous op­po­si­tion of the main re­view­ers, in­clud­ing se­nior of­fi­cials who ap­pealed Janet Wood­cock’s lone in­sis­tence on an ac­cel­er­at­ed ap­proval.

They didn’t see much mer­it in Sarep­ta’s case, and more of these con­fronta­tions are like­ly on the way now, they note. The two pol­i­cy ex­perts al­so con­clud­ed that the ap­proval threat­ens pa­tients and oth­er com­pa­nies that stuck with FDA guide­lines re­quir­ing much more rig­or­ous da­ta. They wrote:

Speed­ing drugs to mar­ket based on such bio­mark­er out­comes can ac­tu­al­ly lead to a worse out­come for pa­tients, even those with life-threat­en­ing dis­eases, if a prod­uct con­fers no mean­ing­ful ben­e­fit and car­ries a risk of ad­verse ef­fects and a high cost. Im­me­di­ate­ly af­ter ap­proval, the man­u­fac­tur­er an­nounced a price of $300,000 per year for eteplirsen. This ap­proach al­so un­fair­ly pe­nal­izes man­u­fac­tur­ers that pur­sue a more rig­or­ous course of de­vel­op­ment us­ing more clin­i­cal­ly rel­e­vant end points, while re­ward­ing com­peti­tors that sub­mit tri­als that have less ev­i­dence sup­port­ing ef­fi­ca­cy.

The ex­perts al­so raised fur­ther con­cerns about a drug that re­lied on a ve­he­ment cam­paign by pa­tient ad­vo­cates and the way in which the reg­u­la­tor should ap­proach the anec­do­tal sup­port pro­vid­ed by pa­tients and their fam­i­lies in tiny, un­con­trolled stud­ies.

Echo­ing re­marks from NYU’s Art Ca­plan, who re­cent­ly out­lined his thoughts in an in­ter­view with me, Kessel­heim and Avorn are al­so look­ing for a new ap­proach that can pro­vide a bet­ter frame­work for more such ap­provals, in­clud­ing pro­grams that of­fer these drugs at cost, rather than with a big prof­it built in.

Pa­tients with DMD need bet­ter treat­ments, and drugs like eteplirsen might one day fill that role. For now, though, the drug has pro­vid­ed a wor­ri­some mod­el for the next gen­er­a­tion of mol­e­c­u­lar­ly tar­get­ed ther­a­pies: demon­strate a slight dif­fer­ence in a lab­o­ra­to­ry test, ac­ti­vate the pa­tient com­mu­ni­ty, win ap­proval, and charge high prices, while re­ly­ing on lim­it­ed reg­u­la­to­ry fol­low-up.

The FDA’s John Jenk­ins re­cent­ly out­lined just why the FDA needs to stick with rig­or­ous de­vel­op­ment re­quire­ments, not­ing that Sarep­ta’s cam­paign was “NOT” a good mod­el for oth­ers to fol­low. But what Kessel­heim, Avorn and Ca­plan are say­ing is that the dis­cus­sion about the fall­out from the Sarep­ta de­ci­sion is just be­gin­ning, no mat­ter how much top reg­u­la­tors would like to put it be­hind the agency.

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.

Paul Hudson (Getty Images)

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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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.

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.

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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