FDA chief Got­tlieb is build­ing a reg­u­la­to­ry speed­way to ac­cel­er­ate gene ther­a­py de­vel­op­ment

In a ral­ly­ing cry for gene ther­a­py, FDA Com­mis­sion­er Scott Got­tlieb says he’s de­ter­mined to clear the path­way for drug de­vel­op­ers in a move to ac­cel­er­ate the first wave of gene ther­a­pies point­ed to the mar­ket.

The first ther­a­peu­tic area to ben­e­fit from new sur­ro­gate end­points will be he­mo­phil­ia, Got­tlieb said — im­me­di­ate­ly ring­ing a bell for com­pa­nies like Spark Ther­a­peu­tics $ONCE, Pfiz­er $PFE, Bio­Marin $BM­RN and uniQure $QURE, which are de­vel­op­ing cures for both ver­sions of the bleed­ing dis­or­der. Un­der the yet-to-be-an­nounced guide­lines, fac­tor pro­duc­tion may in some cas­es be suf­fi­cient as a mea­sure of ben­e­fit.

Got­tlieb dis­cussed the FDA’s pol­i­cy plans for gene ther­a­py Tues­day at the an­nu­al board meet­ing of the Al­liance for Re­gen­er­a­tive Med­i­cine. Quot­ing an MIT study that pre­dicts 40 FDA-ap­proved gene ther­a­py prod­ucts by the end of 2022, he ac­knowl­edged both the “breath­tak­ing” pace of progress and his agency’s role in fa­cil­i­tat­ing it all.

“FDA has more than 500 ac­tive in­ves­ti­ga­tion­al new drug ap­pli­ca­tions in­volv­ing gene ther­a­py prod­ucts,” Got­tlieb said. “We’ve re­ceived more than one hun­dred such ap­pli­ca­tions last year alone. This shows the in­ten­si­ty of sci­en­tif­ic work go­ing on in this field.”

To speed things along, Got­tlieb sug­gest­ed, cer­tain gene ther­a­pies may qual­i­fy for the re­gen­er­a­tive med­i­cine ad­vanced ther­a­py (RMAT) des­ig­na­tion — a sta­tus es­tab­lished by the 21st Cen­tu­ry Cures Act that con­fers all the ben­e­fits of fast track and break­through des­ig­na­tions. De­vel­op­ers may al­so even­tu­al­ly ap­ply for ac­cel­er­at­ed ap­proval, where the FDA would be will­ing to ac­cept more un­cer­tain­ty in ex­change for promis­ing ther­a­pies in “dev­as­tat­ing dis­eases.” Longterm ef­fec­tive­ness — or even tra­di­tion­al mea­sure­ments, such as the demon­stra­tion of a re­duc­tion in bleed­ing rates in he­mo­phil­ia — could come in post­mar­ket fol­low-ups.

“The use of reg­istries and re­al-world ev­i­dence are like­ly to play an in­creas­ing­ly im­por­tant role in this re­spect,” the com­mis­sion­er said. “Part of our goal is to move to­ward a sys­tem that al­lows more re­al-time sur­veil­lance of safe­ty ques­tions af­ter new prod­ucts are ap­proved.”

But that still leaves the in­her­ent prob­lems in de­vel­op­ing and com­mer­cial­iz­ing gene ther­a­pies to be solved.

When you com­pare re­views of cell and gene ther­a­pies from those of tra­di­tion­al drugs, Got­tlieb point­ed out, you see that the break­down of clin­i­cal ver­sus prod­uct is­sues is al­most com­plet­ed in­vert­ed. For these ther­a­pies, clin­i­cal ef­fi­ca­cy is of­ten es­tab­lished ear­ly, thus tak­ing up on­ly 20% of the re­view, while re­view­ers of­ten de­vote 80% of the process to work out man­u­fac­tur­ing and qual­i­ty con­cerns.

Got­tlieb spot­light­ed two man­u­fac­tur­ing-re­lat­ed is­sues hin­der­ing the de­vel­op­ment of gene ther­a­py. The in­ef­fi­cient process of pro­duc­ing gene ther­a­py vec­tors — the lentivirus­es and ade­no-as­so­ci­at­ed virus­es that de­liv­ers the “cor­rect” copies of genes to pa­tients — makes it pro­hib­i­tive­ly ex­pen­sive. Fur­ther­more, the con­ven­tion­al phar­ma par­a­digm, which sep­a­rates ear­ly-stage pi­lot man­u­fac­tur­ing from the com­mer­cial process, means some treat­ments would be caught up, or even aban­doned, in the tran­si­tion.

The FDA is try­ing to help on that front, through an ini­tia­tive to im­prove the yield of cell lines and by “ac­tive­ly pur­su­ing new in­vest­ments” in con­tin­u­ous man­u­fac­tur­ing (as op­posed to batch man­u­fac­tur­ing) plat­forms.

With a field that’s mov­ing ahead rapid­ly and a tech­nol­o­gy that’s go­ing to “trans­form med­i­cine and hu­man health,” the FDA is keen to ad­dress any chal­lenges in man­u­fac­tur­ing and clin­i­cal de­vel­op­ment, Got­tlieb said.


Im­age: Scott Got­tlieb.

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

Up­dat­ed: As­traZeneca jumps deep­er in­to cell ther­a­py 2.0 space with $320M biotech M&A

Right from the start, the execs at Neogene had some lofty goals in mind when they decided to try their hand at a cell therapy that could tackle solid tumors.

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Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

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Emily Leproust, Twist Bioscience CEO

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Illustration: Assistant Editor Kathy Wong for Endpoints News

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Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

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Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

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Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and DN­Di aim to elim­i­nate sleep­ing sick­ness in Africa with promis­ing Ph II/III re­sults for new drug

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

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Digital render of CPI's Medicines Manufacturing Innovation Centre in Glasgow, Scotland (Image: uk-cpi.com)

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Pro­tect­ing its megablock­buster, Janssen chal­lenges Am­gen's Ste­lara biosim­i­lar ahead of planned 2023 launch

Johnson & Johnson unit Janssen on Wednesday sued Amgen over the company’s proposed biosimilar to its megablockbuster Stelara (ustekinumab), after Amgen said it was ready to launch next May or as soon as the FDA signs off on it.

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