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.

Part club, part guide, part land­lord: Arie Bellde­grun is blue­print­ing a string of be­spoke biotech com­plex­es in glob­al boom­towns — start­ing with Boston

The biotech industry is getting a landlord, unlike anything it’s ever known before.

Inspired by his recent experiences scrounging for space in Boston and the Bay Area, master biotech builder, investor, and global dealmaker Arie Belldegrun has organized a new venture to build a new, 250,000 square foot biopharma building in Boston’s Seaport district — home to Vertex and a number of up-and-coming biotech players.

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Novotech CRO Ex­pands Chi­na Team as Biotech De­mand for Clin­i­cal Tri­als In­creas­es up to 79%

An increase in demand of up to 79% for clinical trials in China has prompted Novotech the Asia-Pacific CRO to rapidly expand the China team, appointing expert local clinical executives to their Shanghai and Hong Kong offices. The company is planning to expand their team by 30% over the next quarter.

Novotech China has seen considerable demand recently which is borne out by research from GlobalData:
A global migration of clinical research is occurring from high-income countries to low and middle-income countries with emerging economies. Over the period 2017 to 2018, for example, the number of clinical trial sites opened by biotech companies in Asia-Pacific increased by 35% compared to 8% in the rest of the world, with growth as high as 79% in China.
Novotech CEO Dr John Moller said China offers the largest population in the world, rapid economic growth, and an increasing willingness by government to invest in research and development.
Novotech’s 23 years of experience working in the region means we are the ideal CRO partner for USA biotechs wanting to tap the research expertise and opportunities that China offers.
There are over 22,000 active investigators in Greater China, with about 5,000 investigators with experience on at least 3 studies (source GlobalData).

H1 analy­sis: The high-stakes ta­ble in the biotech deals casi­no is pay­ing out some record-set­ting win­nings

For years the big trend among dealmakers at the major players has been centered on ratcheting down upfront payments in favor of bigger milestones. Better known as biobucks for some. But with the top 15 companies competing for the kind of “transformative” pacts that can whip up some excitement on Wall Street, with some big biotechs like Regeneron now weighing in as well, cash is king at the high stakes table.

We asked Chris Dokomajilar, the head of DealForma, to crunch the numbers for us, looking over the top 20 deals for the past decade and breaking it all down into the top alliances already created in 2019. Gilead has clearly tipped the scales in terms of the coin of the bio-realm, with its record-setting $5 billion upfront to tie up to Galapagos’ entire pipeline.

Dokomajilar notes:

We’re going to need a ‘three comma club’ for the deals with over $1 billion in total upfront cash and equity. The $100 million-plus club is getting crowded at 164 deals in the last decade with new deals being added towards the top of the chart. 2019 already has 14 deals with at least $100 million in upfront cash and equity for a total year-to-date of over $9 billion. That beats last year’s $8 billion and sets a record.

Add upfronts and equity payments and you get $11.5 billion for the year, just shy of last year’s record-setting $11.8 billion.

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UP­DAT­ED: With loom­ing ‘apoc­a­lypse of drug re­sis­tance,’ Mer­ck’s com­bi­na­tion an­tibi­ot­ic scores FDA ap­proval on two fronts

Merck — one of the last large biopharmaceuticals companies in the beleaguered field of antibiotic drug development — on Wednesday said the FDA had sanctioned the approval of its combination antibacterial for the treatment of complicated urinary tract and intra-abdominal infections.

To curb the rise of drug-resistant bacteria and maintain the efficacy of the therapy, Recarbrio (and other antibacterials) — the drug must be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible gram-negative bacteria, Merck $MRK said.

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John McHutchison in 2012. Getty Images

The $1.1M good­bye: Gilead CSO John McHutchi­son is out as Daniel O’Day shakes up the se­nior team

Just a little more than a year after John McHutchison grabbed a promotion to become CSO at Gilead in the wake of Norbert Bischofberger’s exit, he’s out amid a shakeup of the senior team that is also triggering the departure of two other top execs.

Gilead stated that McHutchison “has decided to step down” from the job as of August 2nd. And their SEC filing notes that he’ll be getting a $1.1 million check to settle up on his contract.

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Thomas Gajewski, David Steinberg. (CRI, Pyxis)

Bay­er, Long­wood back star re­searcher's deep dive in­to the tu­mor mi­croen­vi­ron­ment for new I/O tar­gets

From PD-1 targeting to the RAS pathway to the STING complex, Thomas Gajewski has spent the past two decades of his career decoding the various ways the immune system can be unleashed to defend against cancer. So when the University of Chicago professor comes around to putting all his findings into a new platform for finding new targets, VCs and pharma groups alike pay attention.

“He’s been studying T cells for 20 years, plus he’s one of the world’s leaders if not the world leader in the space,” David Steinberg, partner at Longwood Fund, said. “Furthermore, let me add he did a lot of the foundational research and also some of the seminal clinical trials in the existing set of I/O agents. He understands the space really well, he understands the current strengths, and I think he understood really well what was missing, so he knew where to look.”

Kamala Harris speaking yesterday at the Des Moines Register Iowa Presidential Candidate Forum [via Getty]

Who’s the tough­est on drug prices? A game of po­lit­i­cal one-up­man­ship is dri­ving the pol­i­cy de­bate in Wash­ing­ton

Earlier this week we got a look at Senator Kamala Harris’ position on drug prices. She’s proposing that HHS take an average price from single-payer systems like the UK, Germany and Canada — which leverage market access for lower prices — and use that to set the US price. Anything drug companies collect above that would be taxed at a rate of 100%.

And the rhetoric is scathing:
While families struggle to make it to the end of the month, pharmaceutical companies are turning record profits. They’re spending nearly as much on advertising as R&D. They’re manipulating their market power to hike prices on lifesaving generic drugs. They’re making twice the profit of the average industry in America and still increased drug prices by 10.5% over the past six months alone. Meanwhile, they are charging dramatically higher prices to American consumers.
That’s an escalation on Joe Biden’s plan, which includes drug importation from those cheaper markets as well as allowing Medicare to negotiate prices — something that virtually all Dems agree on now.

SJ Lee [File photo]

Go­ing in­side cells, Sung Joo Lee has sketched some big goals for his small — but glob­al — team of drug hunters

For a small biotech based in South Korea with a research arm in Cambridge, MA, Orum Therapeutics has sketched out some big goals aimed at developing antibodies for intracellular targets. And now they have a new $30 million round to push the work forward, aiming at a slate of currently undruggable quests.

Orum has been working on a platform tech out of Ajou University that relies on endocytosis to smuggle antibodies and their cargo inside a cell. They’ve published work in Nature that illustrates its preclinical potential in RAS mutations, and KRAS is on their list of targets. 

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Astel­las buys in­to Fre­quen­cy's re­gen­er­a­tive med strat­e­gy with a $625M al­liance on hear­ing loss

The executive team at Frequency Therapeutics never oversold the results of their maiden Phase I/II study for a new drug to rectify hearing loss. It was, they said back in April, primarily about safety and tolerability, where their drug FX-322 performed as they had hoped. 

That early glimpse of efficacy everyone searches for in their first try on humans? 

(I)mprovements in hearing function, including audiometry and word scores, were observed in multiple FX-322 treated patients.

We don’t know exactly what that means. But whatever the details, Astellas found enough in the data to jump in with a sizable collaboration deal.

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