FDA ad­vis­ers back No­var­tis’ game-chang­ing per­son­al­ized CAR-T for can­cer, ap­proval in sight

The FDA’s ad­vi­so­ry com­mit­tee on can­cer drugs has of­fered a group thumbs-up for No­var­tis’ trail­blaz­ing CAR-T CTL019 (ti­s­agen­le­cleu­cel), mark­ing a key mile­stone for the phar­ma gi­ant as it nears the like­ly launch of a ground­break­ing per­son­al­ized cell ther­a­py for B-cell acute lym­phoblas­tic leukemia.

These out­side ex­perts at the FDA vot­ed 10 to 0 to urge an ap­proval for this drug, of­fer­ing some key sup­port af­ter reg­u­la­tors care­ful­ly re­viewed the com­plex man­u­fac­tur­ing process as well as the safe­ty and ef­fi­ca­cy pro­files of this ther­a­py.

Key to No­var­tis’ suc­cess was the high re­mis­sion rate as well as 6-month and 12-month sur­vival da­ta for chil­dren and young adult pa­tients who were run­ning out of op­tions. The pa­tient num­bers were small, but the re­spons­es were ex­tra­or­di­nary for the pa­tients who re­spond­ed, with an 83% over­all re­mis­sion rate and 79% over­all sur­viv­abil­i­ty rate at 12 months – hit­ting the pri­ma­ry end­point.

“This is a nov­el ther­a­py, there’s an un­met med­ical need, a strong ef­fi­ca­cy and a good risk mit­i­ga­tion strat­e­gy,” not­ed com­mit­tee mem­ber James Gul­ley from the Na­tion­al Can­cer In­sti­tute.

Alan Rein from the Cen­ter for Can­cer Re­search cit­ed the drug’s “re­mark­able clin­i­cal suc­cess­es,” though he not­ed some lin­ger­ing con­cerns with the long-term risks in­volved. And oth­ers echoed those re­marks, rais­ing the prospect that CAR-T can be a game-chang­er in this field.

David Leb­wohl

David Leb­wohl, No­var­tis’ chief of the CTL019 pro­gram, told the pan­el ear­li­er in the day that these out­comes were un­like any­thing he’d seen in 20 years of prac­tice.

But this ther­a­py is al­so linked with threat­en­ing side ef­fects. While pa­tients on this en­gi­neered CAR cell ther­a­py have been re­peat­ed­ly hit by po­ten­tial­ly lethal cas­es of cy­tokine re­lease syn­drome and neu­ro­log­i­cal tox­i­c­i­ty with the threat of new ma­lig­nan­cies, ad­vis­ers were clear­ly will­ing to ac­cept the risk in or­der to achieve the po­ten­tial gains. There were no cas­es of cere­bral ede­ma, in­ves­ti­ga­tors not­ed, but oth­er CAR-Ts have been linked to such cas­es.

No­var­tis al­so not­ed the death of a pa­tient from a cere­bral he­m­or­rhage. Al­so, 9 pa­tients had to dis­con­tin­ue the tri­al af­ter CTL019 couldn’t be man­u­fac­tured for them – a key short­fall that No­var­tis will have to man­age care­ful­ly if it gets a green light for man­u­fac­tur­ing.

Sev­er­al of the com­mit­tee mem­bers, though, of­fered No­var­tis a vote of con­fi­dence on their risk mit­i­ga­tion strat­e­gy and the abil­i­ty of spe­cial­ists in the field to han­dle side ef­fects.

The last three years of de­vel­op­ment work at No­var­tis has been marked by or­ga­ni­za­tion­al re­struc­tur­ing along with the ad­vance and re­treat of ri­val ther­a­pies – all while sort­ing through a threat­en­ing list of tox­i­c­i­ty fac­tors. But No­var­tis’ team main­tained their lead, de­liv­er­ing on a promise No­var­tis CEO Joe Jimenez made to per­sist with the de­vel­op­ment of a dra­mat­ic new ap­proach to treat­ing can­cer.

Ob­servers crowd­ed in­to the FDA’s pre­sen­ta­tion room this morn­ing, rub­bing shoul­ders with CAR-T celebs like Penn’s Carl June with many, many more look­ing on on­line. But the re­view in­volves more than just one ther­a­py at one com­pa­ny. The ad­vis­ers gath­ered at a time that the FDA has com­mit­ted it­self to ac­cel­er­at­ing the de­vel­op­ment of ma­jor new ther­a­pies un­der new FDA com­mis­sion­er Scott Got­tlieb, and CTL019 will be viewed as a test case for the agency’s open­ness to new ther­a­pies that are not yet thor­ough­ly probed in ad­vanced clin­i­cal tri­als.

The vote al­so un­der­scores ODAC’s in­grained ac­cep­tance of mod­er­ate risk when it comes to treat­ing pa­tients dy­ing of can­cer.

Close on No­var­tis’ heels is a team from Kite, a CAR-T-fo­cused biotech which had hoped to be the first to the mar­ket. Kite to­day got a front row seat to the way the agency views these ther­a­pies, and it’s like­ly to take ad­van­tage of that in its own up­com­ing reg­u­la­to­ry re­view.

Be­hind them comes Juno, with a new lead drug, and a group of play­ers like Cel­lec­tis, which are in the ear­ly stages of de­vel­op­ing what they hope can be off-the-shelf ther­a­pies that should be less ex­pen­sive to make and mar­ket.

Fangliang Zhang, AP Images

Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.