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.

In a sec­ond big set­back for Covid-19 an­ti­body treat­ment hopes, Re­gen­eron halts en­roll­ment for more se­vere pa­tients

Regeneron has just delivered more bad news for the hope that neutralizing antibodies could be used to treat patients with more severe forms of Covid-19.

The New York biotech said today that an independent monitoring committee recommended halting enrollment of patients who need high-flow oxygen or mechanical ventilation in one of the trials on their antibody cocktail, after finding “a potential safety signal” and “an unfavorable risk/benefit profile.” The news comes a week after the NIH scrapped a trial of Eli Lilly’s Covid-19 antibody after finding it was having little effect on an initial cohort of hospitalized patients.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 93,000+ biopharma pros reading Endpoints daily — and it's free.

Daphne Koller, Getty

Bris­tol My­er­s' Richard Har­g­reaves pays $70M to launch a neu­rode­gen­er­a­tion al­liance with a star play­er in the ma­chine learn­ing world

Bristol Myers Squibb is turning to one of the star upstarts in the machine learning world to go back to the drawing board and come up with the disease models needed to find drugs that can work against two of the toughest targets in the neuro world.

Daphne Koller’s well-funded insitro is getting $70 million in cash and near-term milestones to use their machine learning platform to create induced pluripotent stem cell-derived disease models for ALS and frontotemporal dementia.

Bel­licum slash­es 79% of staffers af­ter ear­ly da­ta quash hope around next-gen CAR-T

Bellicum Pharmaceuticals tried to make it work.

Over the past months the Houston-based CAR-T player sold its manufacturing facility to MD Anderson — transferring 35 employees in the process — in favor of an outsourced arrangement and completed a reverse stock split, while dribbling out new data and getting an IND cleared.

But new interim data from a Phase I/II trial provided the last straw. Bellicum disclosed late Thursday that it will be laying off 79% of its staff, shaving the workforce from 68 to just 14 by the end of 2020.

No­vo Nordisk qui­et­ly nabs a rare 'break­through' sta­tus in NASH for its cash cow

Earlier this month, the small French biotech Inventiva touted themselves as having won the first FDA breakthrough designation in NASH since Intercept grabbed the first one back in 2015, before the disease had become one of biotech’s hottest areas. Unbeknownst to them, though, a much larger European rival had already landed the status months prior.

Novo Nordisk, the Danish metabolic giant, disclosed in their Q3 report Friday that back in August, the FDA gave them breakthrough status for semaglutide, their blockbuster diabetes drug, in NASH, or non-alcoholic steatohepatitis. The designation sets Novo up as a leading contender in a new wave of companies developing treatments for a silent and widespread disease that, despite a series of setbacks, is still viewed by many as a huge potential market.

Patrick Soon-Shiong at the JP Morgan Healthcare Conference, Jan. 13, 2020 (David Paul Morris/Bloomberg via Getty Images)

Af­ter falling be­hind the lead­ers, dissed by some ex­perts, biotech show­man Patrick Soon-Sh­iong fi­nal­ly gets his Covid-19 vac­cine ready for a tri­al. But can it live up to the hype?

In January, when dozens of scientists rushed to start making a vaccine for the then-novel coronavirus, they were joined by an unlikely compatriot: Patrick Soon-Shiong, the billionaire doctor most famous for making big, controversial promises on cancer research.

Soon-Shiong had spent the last 4 years on his “Cancer Moonshot,” but part of his project meant buying a small Seattle biotech that specialized in making common-cold vectors, called adenoviruses, to train the immune system. The billionaire had been using those vectors for oncology, but the company had also developed vaccine candidates for H1N1, Lassa fever and other viruses. When the outbreak began, he pivoted.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 93,000+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis buys a new gene ther­a­py for vi­sion loss, and this is one pre­clin­i­cal ven­ture that did­n't come cheap

Cyrus Mozayeni got excited when he began to explore the academic work of Ehud Isacoff and John G. Flannery at UC Berkeley.

Together, they were engaged in finding a gene therapy approach to pan-genotypic vision restoration in patients with photoreceptor-based blindness, potentially restoring the vision of a broad group of patients. And they did it by using a vector to deliver the genetic sequence for light sensing proteins.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 93,000+ biopharma pros reading Endpoints daily — and it's free.

As­traZeneca sells off heart fail­ure and hy­per­ten­sion drugs to Chep­lapharm for $400M

Out with the old and in with the new: AstraZeneca is selling off two heart failure and hypertension drugs to Germany-based Cheplapharm, bagging $400 million and making way for development in other areas.

Cheplapharm paid $200 million for the European rights to Atacand (candesartan cilexetil) and Atacand Plus (candesartan cilexetil and hydrochlorothiazide) back in 2018. They’re now doubling that amount for commercial control in more than 70 countries.

News brief­ing: Ax­o­vant faces months of de­lay on lead Parkin­son's gene ther­a­py; Chi­nese CAR-T biotech nabs $100M

One of Axovant’s top gene therapy prospects for its second act is hitting a roadblock that could push its clinical timelines back by almost a year.

In an update, the biotech said it was informed about delays in CMC data and third-part fill-finish issues around mid-October by its manufacturing partner, Oxford Biomedica. Axovant has been developing a suspension-based process for the Parkinson’s drug; with that taking longer than expected, it now believes “it is unlikely that its planned randomized, sham-controlled trial of AXO-Lenti-PD will enroll patients by the end of calendar year 2021.”

Ugur Sahin, BioNTech CEO (Andreas Arnold/picture-alliance/dpa/AP Images)

Covid-19 roundup: Flush with $486M con­tract, As­traZeneca signs Lon­za up to man­u­fac­ture an­ti­bod­ies; BioN­Tech's Ugur Sahin ex­pects vac­cine da­ta 'in a fort­night'

Days after scoring a $486 million BARDA contract to develop and manufacture its long-acting antibody combo for Covid-19, AstraZeneca has tapped Lonza to produce the drug substance at its mid-scale facility in Portsmouth, NH.

The drug, dubbed AZD7442, puts together two antibodies, first discovered by scientists at Vanderbilt University Medical Center, derived from convalescent patients who recovered from a SARS-CoV-2 infection. AstraZeneca licensed them in June and has since further engineered them with half-life extension and reduced Fc receptor binding.