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.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

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Mathai Mammen, FogPharma's next CEO

Math­ai Mam­men hands in J&J's R&D keys to lead Greg Ver­dine’s Fog­Phar­ma 

In the early 1990s, Mathai Mammen was a teaching assistant in Greg Verdine’s Science B46 course at Harvard. In June, the former R&D head at Johnson & Johnson will succeed Verdine as CEO, president and chair of FogPharma, the same month the seven-year-old biotech kickstarts its first clinical trial.

After leading R&D at one of the largest drugmakers in the world, taking the company through more than half a dozen drug approvals in the past few years, not to mention a Covid-19 vaccine race, Mammen departed J&J last month and will take the helm of a Cambridge, MA biotech attempting to go after what Verdine calls the “true emperor of all oncogenes” — beta-catenin.

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Sen­ate Fi­nance Com­mit­tee lobs more bi­par­ti­san pres­sure on­to PBMs

Congress is honing in on how it wants to overhaul the rules of the road for pharmacy benefit managers, with a Senate Finance Committee hearing Thursday serving as the latest example of the Hill’s readiness to make changes to how pharma middlemen operate.

While pledging to ensure patients and pharmacies “don’t get a raw deal,” Finance Committee Chair Ron Wyden (D-OR) laid out the beginning of what looks like a major bipartisan effort — moves the PBM industry is likely to challenge vigorously.

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Nicklas Westerholm, Egetis Therapeutics CEO

Ac­qui­si­tion talks on­go­ing for Swedish rare dis­ease biotech Egetis, shares up al­most 40%

Shares of the Sweden-based rare disease biotech Egetis Therapeutics skyrocketed on Thursday afternoon as the company said it’s engaged in “ongoing discussion” with external parties regarding a “potential acquisition.”

Egetis confirmed rumors with a statement on Thursday while noting that there is no certainty that a takeover offer will be made.

Nonetheless, the possibility of an acquisition has shot up Egetis’ share price. By the afternoon on Thursday, its stock price was {$EGTX.ST} up over 38%. An Egetis spokesperson told Endpoints News in an email that it has no further comments.

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Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

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J&J bows out of RSV vac­cine race, end­ing PhI­II study and ced­ing to Pfiz­er, GSK

Johnson & Johnson announced Wednesday morning it is ending development of its adult RSV vaccine that was in the middle of a 27,200-patient trial, giving up a big slice of what’s expected to be the next multibillion-dollar pharma market.

The decision came down to the shifting RSV “competitive landscape,” a company spokesperson tells Endpoints News, adding the “breadth of options” was much different than when J&J first started its pivotal study. The spokesperson declined to comment on the Phase III data, saying only the shot is undergoing an “ongoing assessment.”

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No longer ‘dead or just hi­ber­nat­ing,’ drug­mak­ers re­turn to heart med­i­cines

In 2015, now-FDA Commissioner Robert Califf joined industry, academic and regulatory representatives in Washington to discuss why more drugs weren’t in development for cardiovascular diseases, the leading US cause of death and once a mainstay of pharmaceutical industry blockbusters.

The group pointed to many reasons. Clinical trials could take years and testing was expensive. Wide availability of generic drugs made the commercial prospects uncertain. Their paper title summed up the mood: “Cardiovascular Drug Development: Is it Dead or Just Hibernating?”

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Lu­pus drug de­vel­op­ment mar­ket heat­ing up, while FDA links with ad­vo­ca­cy group to fur­ther ac­cel­er­ate re­search

The long-underserved systemic lupus erythematosus (SLE) market is suddenly buzzing with treatment possibilities. Less than two years after AstraZeneca’s approval for Saphnelo — the first new SLE drug in a decade and joining just one other approved in GSK’s Benlysta – the pipeline of potential drugs numbers in the dozens.

Although most are very early stage — Spherix Global Insights estimates five in Phase II/III — the pharma R&D enthusiasm is catching on among doctors, patients and advocacy groups. On Wednesday, the Lupus Research Alliance and the FDA formed a novel private-public partnership called Lupus Accelerating Breakthroughs Consortium (Lupus ABC) to help advance lupus clinical trial success.

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Af­ter safe­ty re­view, EMA mir­rors FDA with up­dat­ed rec­om­men­da­tions for JAK in­hibitors

The EMA released updated recommendations today for the use of JAK inhibitors (JAKi) after reviewing data from several clinical trials that showed increased incidents of issues in certain patients who have rheumatoid arthritis and other risk factors.

The EMA noted malignancy, major adverse cardiovascular events (MACE), serious infections, venous thromboembolism (VTE) and mortality in some patients.