The top 10 or­phan drugs in the late-stage pipeline

Or­phan drugs have come in­to the spot­light, scar­ing up head­lines in­volv­ing big prices and small pa­tient pop­u­la­tions. Some com­pa­nies have been ac­cused of prof­i­teer­ing by ma­nip­u­lat­ing the FDA’s rules on this — hel­lo, Marathon — but or­phan ther­a­pies re­main a very close­ly watched are­na with some ma­jor new prospects com­ing through the late-stage pipeline. And some of these drugs are of­fer­ing pa­tients re­al hope for the first time.

Every year, Eval­u­ate crunch­es the num­bers on the top prospects in the pipeline, and the com­pa­ny’s ed­i­to­r­i­al arm EP Van­tage in­cludes it in their an­nu­al re­port on or­phan drugs. I’ve picked up their list and re­arranged it by Eval­u­ate’s sales es­ti­mates for 2022.

A word of cau­tion. Sales es­ti­mates are easy to make and hard to de­liv­er on, so it’s al­ways im­por­tant to take these num­bers with a grain of salt. Al­so, some of these drugs still face big ques­tions as they come un­der FDA re­view. And the FDA re­view process it­self may well change rad­i­cal­ly, es­pe­cial­ly for or­phan drugs, as Pres­i­dent Trump de­mands faster re­sponse times on this front.

It’s still ear­ly to be count­ing chick­ens, but these eggs de­serve care­ful at­ten­tion.

Tesaro: ni­ra­parib, PARP/can­cer
2022 sales: $1.8B

Two years made a big dif­fer­ence for Tesaro $TSRO. In 2015, Eval­u­ate fore­cast­ed this drug would bring in $499 mil­lion in 2020. Now un­der re­view as the biotech ex­plores a broad la­bel, an­a­lysts have been hik­ing their pro­jec­tions, which keeps this com­pa­ny on most an­a­lysts’ lists of like­ly takeover tar­gets. Ovar­i­an can­cer qual­i­fied this drug for or­phan sta­tus.

Kite Phar­ma: ax­i­ab­ta­gene ciloleu­cel, CAR-T/can­cer
2022 sales: $1.7B

Kite’s new name for KTE-C19, its top CAR-T in the pipeline, is a tongue twister, but af­ter the biotech un­veiled 6-month da­ta on Tues­day, we should all learn how to pro­nounce it. The first clear ev­i­dence of dura­bil­i­ty leaves Kite $KITE in an im­pres­sive po­si­tion as it looks to beat out No­var­tis with the first gen­er­a­tion of CAR-Ts. It should be quite a ri­val­ry.

Roche: emi­cizum­ab (ACE910)/ he­mo­phil­ia
2022 sales: $1.5B

Maybe we shouldn’t get too far ahead of our­selves on this one. Yes, Roche $RHH­BY has very high ex­pec­ta­tions for this drug. But it’s al­so been plagued by safe­ty ques­tions, which have yet to be ful­ly aired by reg­u­la­tors. A top prospect? You bet. But don’t count on the mon­ey yet.

As­traZeneca: treme­li­mum­ab/CT­LA-4 check­point in­hibitor
2022 sales:  $1.3B

Usu­al­ly men­tioned right along­side dur­val­um­ab, As­traZeneca’s $AZN oth­er check­point, the treme­li­mum­ab com­bo emerges as an ab­solute­ly cen­tral fea­ture in dis­tin­guish­ing the phar­ma gi­ant as it tries to leapfrog some very ad­vanced play­ers like Mer­ck, Bris­tol-My­ers and Squibb. This one is do or die for As­traZeneca, which won or­phan sta­tus for ma­lig­nant mesothe­lioma.

Shire: lanadelum­ab (SHP643)/hered­i­tary an­gioede­ma 
2022 sales:  $1.1B

This was the jew­el in the crown for Shire {SH­PG} when it paid $5.9 bil­lion for Dyax back in late 2015. The drug blocks en­zyme plas­ma kallikrein to treat hered­i­tary an­gioede­ma, and Shire ex­ecs have al­ready in­di­cat­ed that they be­lieve it can reach $2 bil­lion in an­nu­al sales. And last sum­mer this drug fig­ured promi­nent­ly among the top three pro­grams fea­tured by CEO Flem­ming Orn­skov. It has a break­through drug des­ig­na­tion and a shot at glo­ry.

Te­va: SD-809/tar­dive dysk­i­ne­sia
2022 sales:  $1B

Te­va $TE­VA al­ready has had to deal with a se­ri­ous set­back on this drug when the FDA re­ject­ed its ap­pli­ca­tion for Hunt­ing­ton’s chorea last year. But it’s still shoot­ing for a block­buster with a new dri­ve on to get this ap­proved this year for tar­dive dysk­i­ne­sia. A seem­ing­ly per­ma­nent­ly trou­bled com­pa­ny, Te­va needs this win bad­ly. Te­va’s big pro­gram for this drug puts it in a head-to-head show­down with Neu­ro­crine $NBIX, which not­ed re­cent­ly that it filed for an ap­proval on the ri­val drug val­be­nazine. And some an­a­lysts would put Neu­ro­crine’s drug well ahead of Te­va’s on this one.

blue­bird bio: Lenti­Glo­bin/gene ther­a­py
2022 sales:  $969M

Blue­bird $BLUE helped make gene ther­a­py a hot field again, and its strug­gles with vary­ing de­grees of im­pact on pa­tients has helped raise fresh ques­tions about where it’s head­ed on be­ta tha­lassemia, where in­ves­ti­ga­tors are now pur­su­ing a Phase III tri­al. Po­ten­tial? You bet. But there are still plen­ty of unan­swered ques­tions.

As­traZeneca: acal­abru­ti­nib (ACP-196) /BTK in­hibitor 
2022 sales:  $968M

As­traZeneca won’t mind be­ing the on­ly com­pa­ny to make two ap­pear­ances on this top 10 list. This drug came its way when it ac­quired a ma­jor­i­ty in­ter­est in Ac­er­ta in 2015, as Pas­cal So­ri­ot sought to ex­e­cute a ma­jor turn­around in the phar­ma gi­ant’s prospects. With gener­ic com­pe­ti­tion eat­ing away at rev­enue, As­traZeneca needs all the help it can get from its on­col­o­gy pipeline. This drug is in late-stage stud­ies for B-cell blood can­cers.

No­var­tis: CTL019/CAR-T
2022 sales: $917M

This is the “oth­er” CAR-T you prob­a­bly heard about. Af­ter No­var­tis ripped up its cell ther­a­py unit last year, the phar­ma gi­ant went to some trou­ble to try and re­as­sure ob­servers that it was still on track to file for an ap­proval in ear­ly 2017. But an­a­lysts are dis­count­ing its im­pact com­pared to Kite, which re­mains the leader in the field, re­gard­less of who gets to the FDA first.

Ab­b­Vie: veli­parib/PARP in­hibitor
2022 sales: $854M

PARPs are all the rage these days, es­pe­cial­ly since Pfiz­er picked up ta­la­zoparib in its $14 bil­lion Medi­va­tion buy­out. Ab­b­Vie, though, re­mains well be­hind what is be­com­ing a fair­ly crowd­ed field. That leaves them on the list for now, but just bare­ly, as all eyes re­main on Tesaro.

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. But 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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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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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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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.