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.

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

Sanofi out­lines big API plans as coro­n­avirus out­break re­port­ed­ly threat­ens short­age of 150 drugs

As the world becomes increasingly dependant on Asia for the ingredients of its medicines, Sanofi sees business to be done in Europe.

The French drugmaker said it’s creating the world’s second largest active pharmaceutical ingredients (API) manufacturer by spinning out its six current sites into a standalone company: Brindisi (Italy), Frankfurt Chemistry (Germany), Haverhill (UK), St Aubin les Elbeuf (France), Újpest (Hungary) and Vertolaye (France). They have mapped out €1 billion in expected sales by 2022 and 3,100 employees for the new operations headquartered in France.

UP­DAT­ED: NGM Bio takes leap for­ward in crowd­ed NASH field

South San Francisco-based NGM Bio may have underwhelmed with its interim analysis of a key cohort from a mid-stage NASH study last fall — but stellar topline data unveiled on Monday showed the compound induced significant signs of antifibrotic activity, NASH resolution and liver fat reduction, sending the company’s stock soaring.

There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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Mickey Kertesz, KidsandArtOrg via YouTube

Soft­Bank's newest, $165M biotech in­vest­ment looks for in­fec­tious traces in the blood

SoftBank has found its newest biotech investment.

The Japanese bank has invested $165 million into Karius, a company that uses blood tests to diagnose infectious diseases, as part of its new Vision Fund 2. The full scope of the new fund has yet to be announced, but the first and newly-beleaguered Vision Fund poured $100 billion into technology companies, including the biotechs Vir Biotechnology and Roivant and the sequencing company 10x Genomics.

Methicillin-resistant Staph aureus (Shutterstock)

FDA grants ‘break­through’ sta­tus to an­tibi­ot­ic al­ter­na­tive as Con­tra­Fect rush­es to join fight against su­per­bug

An experimental drug that promises to be the first anti-infective agent to prove superior to vancomycin — an antibiotic approved in 1958 — has notched the FDA’s “breakthrough” status.

ContraFect said the designation was based on Phase II data in which exebacase was tested against a superbug known as methicillin-resistant Staph aureus, or MRSA. In a subgroup analysis, the clinical responder rate at day 14 was 42.8% higher than that among those treated with standard of care, the company said (p=0.010).

Zhong Nanshan, CGTN via YouTube

Har­vard joins coro­n­avirus fight with $115 mil­lion and a high-pro­file Chi­nese part­ner

For two months, as the novel coronavirus swelled from a few early cases tied to a Wuhan market to a global epidemic, most of the world’s focus and dollars have flowed toward emergency initiatives: building vaccines at a record pace, plucking experimental antivirals out of freezers to see what sticks and immunizing mice for new antibodies.

Now a new and well-funded collaboration between Harvard and a top Chinese research institute will play the long game. In a 5-year, $115 million initiative backed by China Evergrande Group, researchers from the Harvard Medical School, Harvard T.H. Chan School of Public Health and Guangzhou Institute for Respiratory Health will study the virus in an effort to develop therapies against infections by the novel coronavirus, known as SARS–CoV-2, and to prevent new ones.

No­var­tis gets a boost in block­buster mul­ti­ple scle­ro­sis race with Roche

In the first step of what’s likely to be a long and uphill battle for the drugmaker, the FDA has accepted Novartis’s BLA submission for a new multiple sclerosis drug and given it priority review. The PDUFA date for the potential blockbuster drug is in June.

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Juergen Horn

An­i­mal health vet Juer­gen Horn makes new an­ti­body play for pets, rak­ing $15M in Se­ries A haul

Zoetis forked over $85 million in 2017 to acquire Nexvet Biopharma and its pipeline of monoclonal antibodies. Juergen Horn, Nexvet’s former chief product development officer, has now secured $15 million for his own biologic company for animals: Invetx.

Buoyed by emerging advances in gene therapies for humans, scientists have started looking at harnessing the technology for animals setting up companies such as Penn-partnered Scout Bio and George Church-founded Rejuvenate Bio. But akin to Nexvet, Invetx is working on leveraging the time-tested science of monoclonal antibodies to treat chronic diseases that afflict man’s best friend.

As coro­n­avirus out­break reach­es 'tip­ping point,' GSK lends ad­ju­vant tech to Chi­nese part­ner armed with pre­clin­i­cal vac­cine

As the coronavirus originating out of Wuhan spreads to South Korea, Italy and Iran, stoking already intense fears of a pandemic, GlaxoSmithKline has found another pair of trusted hands to place its adjuvant system. China’s Clover Biopharmaceuticals will add the adjuvant to its preclinical, protein-based vaccine candidate against SARS-CoV-2.

Clover, which is based in the inland city of Chengdu, boasts of a platform dubbed Trimer-Tag that produces covalently-trimerized fusion proteins. Its candidate, COVID-19 S-Trimer, resembles the viral spike (S)-protein found in the virus.