FDA rolls out ex­pec­ta­tions for a loom­ing reg­u­la­to­ry shift for in­sulin and oth­er bi­o­log­ics

Cer­tain bi­o­log­ics will be re­moved from the FDA’s Or­ange Book on 23 March 2020 and in­clud­ed in the Pur­ple Book, and all sub­se­quent fol­low-on ap­pli­cants will not be able to re­ly up­on these new drug ap­pli­ca­tions for ap­proval but will have to win ap­proval as biosim­i­lars un­der new pro­posed rules on biosim­i­lar de­vel­op­ment.

The agency on Tues­day re­leased two new draft Q&A guid­ance doc­u­ments on biosim­i­lar de­vel­op­ment and the “deemed to be a li­cense” pro­vi­sion of the Bi­o­log­ics Price Com­pe­ti­tion and In­no­va­tion Act of 2009 (BP­CIA), as well as two fi­nal guid­ance doc­u­ments on the same top­ics and one pro­posed rule amend­ing the de­f­i­n­i­tion of a bi­o­log­i­cal prod­uct.

The ef­forts are part of the FDA’s decade-long work to be­gin — start­ing in March 2020 — tran­si­tion­ing the ap­proved mar­ket­ing ap­pli­ca­tions for a sub­set of bi­o­log­i­cal prod­ucts, such as in­sulin and hu­man growth hor­mone — which were pre­vi­ous­ly ap­proved as drugs un­der sec­tion 505 of the FD&C Act — to be deemed to be bi­o­log­ics li­cens­es.

The fi­nal guid­ance al­so de­scribes the FDA’s plans for sup­ple­ments to ap­proved NDAs that re­main pend­ing on 23 March 2020. “We in­tend to ad­min­is­tra­tive­ly con­vert these pend­ing NDA sup­ple­ments to pend­ing BLA sup­ple­ments un­der the PHS Act,” the agency said. In­dus­try pre­vi­ous­ly took is­sue with the FDA’s in­ten­tions on the mat­ter.

Got­tlieb Com­ments

While high­light­ing the need to bring down the price of in­sulin, FDA Com­mis­sion­er Scott Got­tlieb ex­plained at the CMS/FDA Sum­mit in Wash­ing­ton DC on Tues­day that the goal of the guid­ances and new poli­cies is two-fold: to min­i­mize spon­sors’ abil­i­ty to game the ex­clu­siv­i­ty pro­vi­sions and fore­stall biosim­i­lar en­try, and to make sure that when drugs tran­si­tion in­to bi­o­log­ics, they do not re­ceive ad­di­tion­al ex­clu­siv­i­ties that they are not en­ti­tled to.

In ad­di­tion to the guid­ance doc­u­ments and pro­posed rule, Got­tlieb ex­plained that the FDA is is­su­ing no­tice of how it will — up­on re­quest — re­view study pro­to­cols sub­mit­ted by biosim­i­lar ap­pli­cants to as­sess whether their pro­to­cols con­tain com­pa­ra­ble safe­ty pro­tec­tions to those in the risk eval­u­a­tion and mit­i­ga­tion strat­e­gy (REMS) for the prod­uct they’re try­ing to ref­er­ence — as ex­plained in the re­vised draft Q&A on biosim­i­lar de­vel­op­ment and the BP­CI Act.

“If re­quest­ed, the FDA will is­sue a let­ter to the ref­er­ence prod­uct hold­er in­form­ing them that com­pa­ra­ble pro­tec­tions ex­ist, and that the FDA won’t con­sid­er it to be a vi­o­la­tion of the brand­ed drug com­pa­ny’s REMS to pro­vide the biosim­i­lar spon­sor with a suf­fi­cient quan­ti­ty of the ref­er­ence prod­uct to per­form test­ing nec­es­sary to sup­port its biosim­i­lar ap­pli­ca­tion,” Got­tlieb said.

Rule and Guid­ance

New ques­tions in the re­vised draft Q&A al­so in­clude more in­for­ma­tion on the na­ture and type of in­for­ma­tion that a spon­sor should pro­vide to sup­port a post-ap­proval man­u­fac­tur­ing change for a li­censed biosim­i­lar prod­uct.

Oth­er new ques­tions, which the agency re­spond­ed no to, in­clude: “May a spon­sor seek ap­proval, in a 351(k) ap­pli­ca­tion or a sup­ple­ment to an ap­proved 351(k) ap­pli­ca­tion, of a route of ad­min­is­tra­tion, a dosage form, or a strength that is not the same as that of the ref­er­ence prod­uct?” and “May a spon­sor seek ap­proval, in a 351(k) ap­pli­ca­tion or a sup­ple­ment to an ap­proved 351(k) ap­pli­ca­tion, for a con­di­tion of use that has not pre­vi­ous­ly been ap­proved for the ref­er­ence prod­uct?”

The oth­er Q&A doc­u­ment fea­tures nu­mer­ous ques­tions and an­swers on biosim­i­lar­i­ty or in­ter­change­abil­i­ty, pro­vi­sions re­lat­ed to the re­quire­ment to sub­mit a BLA for a bi­o­log­i­cal prod­uct, and ex­clu­siv­i­ty.

The fi­nal and draft guid­ances on the “deemed to be a li­cense” pro­vi­sion spell out the tran­si­tion pe­ri­od for the bi­o­log­ics to which the pro­vi­sion ap­plies, how to iden­ti­fy prod­ucts sub­ject to the tran­si­tion, statu­to­ry or reg­u­la­to­ry re­quire­ments for BLAs, and tran­si­tion­ing bi­o­log­ics from the Or­ange to the Pur­ple Book.

The pro­posed rule, mean­while, would amend FDA’s reg­u­la­tion that de­fines “bi­o­log­i­cal prod­uct” to make a tech­ni­cal re­vi­sion and to con­form to the statu­to­ry de­f­i­n­i­tion en­act­ed in the BP­CIA.


Im­age: Scott Got­tlieb SHUT­TER­STOCK

First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

Ryan Watts, Denali CEO

Bio­gen hands De­nali $1B-plus in cash, $1B-plus in mile­stones to part­ner on late-stage Parkin­son’s drug

Biogen is handing over more than a billion dollars cash to partner with the up-and-coming neurosciences crew at Denali on a new therapy for Parkinson’s. And the big biotech is ready to pile on more than a billion dollars more in milestones — if the alliance is a success.

For Biogen $BIIB, the move on Denali’s small molecule inhibitors of LRRK2 puts them in line to collaborate on a late-stage program for DNL151, which is scheduled to start next year.

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President Trump speaks with members of the media before boarding Marine One (AP Images)

'Oc­to­ber is com­ing,' and every­one still wants to know if a Covid-19 vac­cine will be whisked through the FDA ahead of the elec­tion

Right on the heels of a lengthy assurance from FDA commissioner Stephen Hahn that the agency will not rush through a quick approval for a Covid-19 vaccine, the President of the United States has some thoughts on timing he’d like to share.

In an exchange with Fox News’ Geraldo Rivera on Thursday, President Trump allowed that a vaccine could be ready to roll “sooner than the end of the year, could be much sooner.”

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Donald Trump, AP

Trump reach­es for his pen as long-await­ed ex­ec­u­tive or­der on drug man­u­fac­tur­ing on-shoring fi­nal­ly ar­rives — re­ports

President Trump will sign a long-rumored executive order later today that is designed to spur more made-in-the-USA therapies, according to a slate of new reports out Thursday morning.

Drug manufacturing circles have been buzzing about this EO for months now, wondering how Trump plans to require the on-shoring of certain therapies.

According to the Bloomberg report, White House trade adviser Peter Navarro told reporters that the administration will come up with a list of essential medicines Trump wants to have made inside the US. The order will direct government purchasers to buy these essential meds from US suppliers. The reports add that the order relaxes drug safety and environmental regulations to make it happen.

Yvonne Greenstreet, incoming Alnylam president (Alnylam)

Al­ny­lam pres­i­dent Bar­ry Greene leaves af­ter 17 years, hand­ing po­si­tion over to Yvonne Green­street as biotech looks to­ward prof­itabil­i­ty

After 17 years helping Alnylam steer control of buzzy but unproven science they promised could change medicine, president Barry Greene is leaving the RNAi biotech just as that technology is beginning to hit prime time.

Leaving to “pursue outside interests in the biopharmaceutical industry,” the longtime executive will hand over the reins on October 1 to current COO Yvonne Greenstreet. Greenstreet, a former Pfizer and GlaxoSmithKline executive, inherits the high-profile spot at a company that’s proven its tech can work in rare diseases but now faces the daunting task of turning a couple successes and a new mountain of cash into drugs that are broadly applicable and, crucially, profitable.

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Covid-19 roundup: 34 AGs call for ‘march-in’ rights on remde­sivir; Hahn pleads with pub­lic to trust FDA's vac­cine re­view

A bipartisan group of 34 attorneys general have asked the federal government to bypass Gilead’s patent rights on remdesivir and begin scaling and distributing the Covid-19 antiviral, or to allow the states to do it themselves.

In a letter to HHS secretary Alex Azar, the AGs expressed frustrations over the $3,250 price tag Gilead placed on the the drug, citing the federal funding that went into its developments. And they noted the sustained difficulties hospitals have faced in getting supplies from either the California biotech or their contract manufacturer AmerisourceBergen.

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Douglas Fambrough, Dicerna CEO (Boehringer Ingelheim via YouTube)

Roche-backed Dicer­na push­es in­to the pack rac­ing to­ward the block­buster hep B goal line, armed with PhI da­ta

Dicerna has lined up a set of proof-of-concept data from a small cohort of hepatitis B patients in a match-up against some heavyweight rivals which got out in front of this race. And right in the front row you’ll find a team from Roche, which paid $200 million in cash and offered another $1.5 billion in milestones to partner with Dicerna $DRNA on their RNAi program for hep B.

Right now it’s looking competitive, with lots of big challenges ahead.

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UP­DAT­ED: No­vavax her­alds the lat­est pos­i­tive snap­shot of ear­ly-stage Covid-19 vac­cine — so why did its stock briefly crater?

High-flying Novavax $NVAX became the latest of the Covid-19 vaccine players to stake out a positive set of biomarker data from its early-stage look at its vaccine in humans.

Their adjuvanted Covid-19 vaccine was “well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera,” the company noted. According to the biotech:

All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID‑19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.

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Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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