Got­tlieb, Marks de­tail plans to ad­vance de­vel­op­ment of cell and gene ther­a­pies

FDA Com­mis­sion­er Scott Got­tlieb and Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER) Di­rec­tor Pe­ter Marks on Tues­day de­tailed plans for the agency to keep pace with an ex­pect­ed in­flux of ap­pli­ca­tions for cell and gene ther­a­pies over the com­ing years.

“The FDA is wit­ness­ing a surge of cell and gene ther­a­py prod­ucts en­ter­ing ear­ly de­vel­op­ment, ev­i­denced by a large up­swing in the num­ber of in­ves­ti­ga­tion­al new drug (IND) ap­pli­ca­tions,” Got­tlieb and Marks say.

Scott Got­tlieb

By 2020, Got­tlieb and Marks say they ex­pect to be re­ceiv­ing up­wards of 200 INDs for cell and gene ther­a­pies each year, adding to the 800 ac­tive INDs for such prod­ucts al­ready filed with the agency. By 2025, they pre­dict the agency will be ap­prov­ing be­tween 10 and 20 cell and gene ther­a­py prod­ucts an­nu­al­ly.

The two FDA lead­ers draw a com­par­i­son be­tween the cur­rent land­scape for cell and gene ther­a­pies to the pro­lif­er­a­tion of an­ti­body drugs in the late 1990s once plat­forms for cre­at­ing an­ti­bod­ies that wouldn’t be re­ject­ed by a pa­tient’s im­mune sys­tem were wide­ly avail­able.

“In this case, it was the ad­vent of safe and ef­fec­tive vec­tors for the de­liv­ery of gene ther­a­py prod­ucts, such as the adop­tion of ade­no-as­so­ci­at­ed virus (AAV) vec­tors,” Got­tlieb and Marks say.

Pe­ter Marks

To pro­mote the con­tin­ued de­vel­op­ment of new cell and gene ther­a­pies, Got­tlieb and Marks say that the FDA will take a num­ber of steps, in­clud­ing adding as many as 50 ad­di­tion­al re­view­ers to its staff, lever­ag­ing ex­pe­dit­ed path­ways, is­su­ing new guid­ance and tak­ing en­force­ment ac­tion against clin­ics that fail to com­ply with FDA reg­u­la­tions.

Ac­cord­ing to Got­tlieb and Marks, ac­cel­er­at­ed ap­proval is par­tic­u­lar­ly rel­e­vant for gene ther­a­pies as the agency can man­date post­mar­ket stud­ies to mea­sure the dura­bil­i­ty of the treat­ment and long-term safe­ty is­sues that would be dif­fi­cult to ad­dress in the pre­mar­ket set­ting.

As for new guid­ance, Got­tlieb and Marks say the agency will de­vel­op a se­ries of clin­i­cal guid­ance doc­u­ments for dif­fer­ent ar­eas of prod­uct de­vel­op­ment, such as gene ther­a­pies for in­her­it­ed blood dis­or­ders and neu­rode­gen­er­a­tive dis­eases.

In some cas­es, Got­tlieb and Marks say that a more tra­di­tion­al ap­proach to drug de­vel­op­ment may be war­rant­ed for cer­tain gene ther­a­pies, such as those in­tend­ed to ad­dress the symp­toms of a neu­rode­gen­er­a­tive dis­ease or tar­get an “ex­pres­sion of a pro­tein or en­zyme be­lieved to play a role in the ad­vance of the dis­ease.”

In an­oth­er planned guid­ance, Got­tlieb and Marks say the agency will tack­le the man­u­fac­tur­ing com­plex­i­ties of cell-based gene ther­a­pies, such as chimeric anti­gen re­cep­tor (CAR) T-cell ther­a­pies, in a fu­ture guid­ance.

“The guid­ance that we in­tend to is­sue will pro­mote a bet­ter un­der­stand­ing of the crit­i­cal qual­i­ty at­trib­ut­es and oth­er fac­tors re­lat­ed to prod­uct man­u­fac­tur­ing,” they write, adding that one of their goals will be to min­i­mize the need for bridg­ing stud­ies for mi­nor man­u­fac­tur­ing changes for cell ther­a­pies.

The two al­so say that the FDA will is­sue a guid­ance lat­er this year out­lin­ing how re­searchers can “pool their clin­i­cal da­ta af­ter fol­low­ing a com­mon man­u­fac­tur­ing pro­to­col, and there­by de­vel­op a more ro­bust da­ta set for pur­pos­es of gain­ing a [Bi­o­log­ics Li­cense Ap­pli­ca­tion] BLA.”


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.

Con­quer­ing a silent killer: HDV and Eiger Bio­Phar­ma­ceu­ti­cals

Hepatitis delta, also known as hepatitis D, is a liver infection caused by the hepatitis delta virus (HDV) that results in the most severe form of human viral hepatitis for which there is no approved therapy.

HDV is a single-stranded, circular RNA virus that requires the envelope protein (HBsAg) of the hepatitis B virus (HBV) for its own assembly. As a result, hepatitis delta virus (HDV) infection occurs only as a co-infection in individuals infected with HBV. However, HDV/HBV co-infections lead to more serious liver disease than HBV infection alone. HDV is associated with faster progression to liver fibrosis (progressing to cirrhosis in about 80% of individuals in 5-10 years), increased risk of liver cancer, and early decompensated cirrhosis and liver failure.
HDV is the most severe form of viral hepatitis with no approved treatment.
Approved nucleos(t)ide treatments for HBV only suppress HBV DNA, do not appreciably impact HBsAg and have no impact on HDV. Investigational agents in development for HBV target multiple new mechanisms. Aspirations are high, but a functional cure for HBV has not been achieved nor is one anticipated in the forseeable future. Without clearance of HBsAg, anti-HBV investigational treatments are not expected to impact the deadly course of HDV infection anytime soon.

No­var­tis is ax­ing 150 ear­ly dis­cov­ery jobs as CNI­BR shifts fo­cus to the de­vel­op­ment side of R&D

Novartis is axing some 150 early discover jobs in Shanghai as it swells its staff on the drug development side of the equation in China. And the company is concurrently beefing up its investment in China’s fast-growing biotech sector with a plan to add to its investments in local VCs.

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No­var­tis is eye­ing a multi­bil­lion-dol­lar Med­Co buy­out as Jer­sey biotech nears NDA — re­ports

To get from Novartis’ US headquarters to the Medicines Company, you make a left out of a square concrete building on NJ-Route 10, follow it past the sun orange veranda of Jersey’s Hot Bagels and the inexplicable green Vermont cabin that houses the Whippany Railway Museum until you turn right and immediately arrive at a rectangular glass building. It should take you about 12 minutes.

Reports are out that Novartis may be making that trip. Amid a torrent of Phase III data burnishing MedCo’s chances at a blockbuster cholesterol drug,  Bloomberg News is reporting that Novartis is looking to acquire the Jersey-based biotech.

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UP­DAT­ED: In a land­mark first glimpse of hu­man da­ta from Ver­tex, CRISPR/Cas9 gene ther­a­py sig­nals ear­ly ben­e­fit

Preliminary data on two patients with blood disorders that have been administered with Vertex and partner CRISPR Therapeutics’ gene-editing therapy suggest the technology is safe and effective, marking the first instance of the benefit of the use of CRISPR/Cas9 technology in humans suffering from disease.

Patients in these phase I/II studies give up peripheral blood from which hematopoietic stem and progenitor cells are isolated. The cells are tinkered with using CRISPR/Cas9 technology, and the edited cells — CTX001 — are infused back into the patient via a stem cell transplant. The objective of CTX001 is to fix the errant hemoglobin gene in patents with two blood disorders: beta-thalassemia and sickle cell disease, by unleashing the production of fetal hemoglobin.

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Badrul Chowdhury. FDA via Flickr

As­traZeneca los­es an­oth­er ex­ec­u­tive to biotech, as Badrul Chowd­hury moves to Savara

Another executive is migrating from the echelons of Big Pharma to the corridors of small biotech.

In April 2018, Badrul Chowdhury took his more than two decades of experience at the FDA to AstraZeneca, where he took on the role of senior vice president and chief physician-scientist for respiratory, inflammation and autoimmunity late-stage development in biopharmaceuticals R&D.

After about a year and a half in this role, Chowdhury is moving to a small Texas biotech called Savara, where he will serve as chief medical officer.

Yiannis Kiachopoulos and Artur Saudabayev, co-founders of Causaly

Lon­don AI up­start, which counts No­var­tis as a cus­tomer, can teach your com­put­er to read

When Amazon developed a machine-learning tool to make its recruitment process more efficient — the man-made system absorbed the gender-bias of its human makers, and the project was aborted. In the field of biopharmaceuticals, the way researchers train their machine learning algorithms can skew the outcome of predictions. But before those predictions can be made, the engine must learn to read to make sense of explosive volume of knowledge out there.

Burt Adelman. Novo Ventures

Here's a $25M seed fund aimed at back­ing some brash new drug ideas out of the Broad

As a former academic and a seasoned drug developer, Burt Adelman knew when he was recruited as a senior advisor to Novo Ventures in 2017 that one of his key priorities needs to be introducing the fund to the network he was so deeply embedded in.

“I was thinking long and hard on how can I, as a Boston insider, help Novo really get inside the ecosystem of Boston biotech?” he recalled in an interview with Endpoints News.

Welling­ton lines up a $393M bankroll for its next round of pri­vate biotech bets — and they’re like­ly think­ing big

Wellington Management made some uncustomary waves at the beginning of the year when it threw its considerable weight against Bristol-Myers Squibb’s $74 billion Celgene buyout. But after Bristol-Myers’ biggest investor conceded that game to the influential proxy firms involved, they’re now going to end the year by rolling out a big new investment fund for a new stable of fledgling biotechs on the private side of the industry.

As uter­ine race with Ab­b­Vie heats up, My­ovant eyes FDA ap­proval with tri­al re­sults from prostate can­cer

Myovant has long had a secret weapon in its uterine rivalry with AbbVie: Men.

While the small Swiss biotech has jockeyed with the Illinois-based giant for a foothold in the endometriosis and uterine fibroid therapy market, the company has been developing the same lead compound, relugolix, for use in one of the most common cancers for the uterus-less: prostate cancer. Today, Myovant is out with positive topline results from its big Phase III trial on the gonadotropin-releasing hormone (GnRH) antagonist. They say they’ve reached every primary and secondary endpoint with p values less than .0001.