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.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. The idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.

Arde­lyx bags its first FDA OK for IBS, set­ting up a show­down with Al­ler­gan, Iron­wood

In the first of what it hopes will be a couple of major regulatory milestones for its new drug, Ardelyx has bagged an FDA approval to market Ibsrela (tenapanor) for irritable bowel syndrome.

The drug’s first application will be for IBS with constipation (IBS-C), inhibiting sodium-hydrogen exchanger NHE3 in the GI tract in such a way as to increase bowel movements and decrease abdominal pain. This comes on the heels of two successful Phase III trials.

Ver­tex deal for Scot­land — no deal for Eng­land

Cystic fibrosis (CF) drug maker Vertex Pharmaceuticals — which is still locked in negotiation with NHS England to endorse the use of its medicines — has successfully negotiated a deal with Scottish authorities.

A month ago, the Scottish Medicines Consortium spurned two of the company’s medicines — Orkambi and Symkevi — citing uncertainty over their long-term efficacy in relation to their cost.

Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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