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.

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

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Gilead claims Tru­va­da patents in HHS’ com­plaint are in­valid

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.

Gilead dusts off a failed Ebo­la drug as coro­n­avirus spreads; Ex­elix­is boasts pos­i­tive Ph I/II da­ta

→ Less than a year ago Gilead’s antiviral remdesivir failed to make the cut as investigators considered a raft of potential drugs that could be used against an Ebola outbreak. But it may gain a new mission with the outbreak of the coronavirus in China, which is popping up now around the world.

Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.

Alex Karnal (Deerfield)

Deer­field vaults to the top of cell and gene ther­a­py CD­MO game with $1.1B fa­cil­i­ty at Philadel­phi­a's newest bio­phar­ma hub

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.

Tri­fec­ta of sick­le cell dis­ease ther­a­pies ex­tend life ex­pectan­cy, but are not cost-ef­fec­tive — ICER

Different therapeutic traits brandished by the three approved therapies for sickle cell disease all extend life expectancy, but their impact on quality of life is uncertain and their long-term cost-effectiveness is not up to scratch according to the thresholds considered reasonable by ICER, the non-profit concluded in a draft guidance report on Thursday.

Sickle cell disease (SCD), which encompasses a group of inherited red blood cell disorders that typically afflict those of African ancestry, impacts hemoglobin — and is characterized by episodes of searing pain as well as organ damage.