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.

Charles Baum, Mirati CEO

Mi­rati plots a march to the FDA for its KRAS G12C drug, breath­ing down Am­gen’s neck with bet­ter da­ta

Mirati Therapeutics $MRTX took another closely-watched step toward a now clearly defined goal to file for an approval for its KRAS G12C cancer drug adagrasib (MRTX849), scoring a higher response rate than the last readout from the class-leading rival at Amgen but still leaving open a raft of important questions about its future.

Following a snapshot of the first handful of responses, where the drug scored a tumor response in 3 of 5 patients with non-small cell lung cancer, the response rate has now slid to 45% among a pooled group of 51 early-stage and Phase II patients, 43% — 6 of 14 — when looking solely at the Phase I/Ib. Those 14 patients had a median treatment duration of 8.2 months, with half still on therapy and 5 of 6 responders still in response.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: FDA anoints Gilead­'s remde­sivir as the Covid-19 treat­ment win­ner, hand­ing down full ap­proval — de­spite some deep skep­ti­cism

Seven months into the Covid-19 pandemic, the race to develop a treatment for the disease that’s proved to be the biggest health crisis in a century has an officially designated winner: Gilead. And they’re picking up the prize — worth billions in peak sales — despite a major study that concluded the drug was no help in reducing the number of people who die from the virus.

The FDA handed down a thumbs-up for remdesivir, the company announced Thursday afternoon, as the drug becomes the first fully approved treatment for Covid-19 in the US. Remdesivir, to be marketed as Veklury, will come with a label for treatment in adults and children older than 12 in Covid-19 cases that require hospitalization.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Bo Cumbo, AavantiBio CEO (file photo)

Bo Cum­bo jumps from the top com­mer­cial post at Sarep­ta to the helm of a gene ther­a­py start­up with some in­flu­en­tial back­ers, big plans and $107M

After a 7-year stretch building the commercial team at Sarepta, longtime drug salesman Bo Cumbo is jumping to the entrepreneurial side of the business, taking the helm of a startup that’s got several deep-pocket investors. And he’s not just bringing his experience in selling drugs.

He tells me that when he told Sarepta CEO Doug Ingram about it, his boss got excited about the venture and opted to jump in with a $15 million investment from Sarepta to add to the launch money, alongside 3 of the busiest investors in biotech.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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