The num­ber of I/O can­cer drugs in the clin­ic con­tin­ues to swell at an ex­plo­sive pace -- of­fer­ing new hope, fresh con­cerns

The jug­ger­naut of im­muno-on­col­o­gy drug re­search around the world con­tin­ues to rapid­ly gain speed and mass, of­fer­ing pa­tients with vir­tu­al­ly every can­cer type the prospect of new com­bi­na­tions or monother­a­pies that may bend the course of their dis­ease, ac­cord­ing to a new study map­ping the glob­al land­scape of I/O. But it al­so rais­es fresh con­cerns about com­modi­ti­za­tion and pa­tient re­cruit­ment as the num­ber of PD-1/L1s on the mar­ket con­tin­ues to mul­ti­ply, with hun­dreds more com­ing from be­hind in the pipeline.

Vanes­sa Hub­bard-Lucey

A team at the Can­cer Re­search In­sti­tute has been study­ing the field for the past 2 years, track­ing tri­al ac­tiv­i­ty around the globe as I/O con­tin­ues to at­tract block­buster-sized in­vest­ments in pur­suit of new stan­dards of can­cer med­i­cine. And the num­bers at the end of 2018 have swelled sig­nif­i­cant­ly in most cat­e­gories.

Source: Can­cer Re­search In­sti­tute

Click on the im­age to see the full-sized ver­sion

Some of the high­lights from their re­port — which was pub­lished in Na­ture Re­views Drug Dis­cov­ery — in­clude:

— World­wide the num­ber of I/O drugs in 6 key class­es has hit 3,394 — up 67% in one year. Those drugs in­volved 417 tar­gets like CD19, at the top of the list, fol­lowed by PD-1, PD-L1 and HER2. A year ago they were track­ing 2,031 drugs in­volv­ing 273 tar­gets.

— The group count­ed 2,250 clin­i­cal tri­als un­der­way for PD-1/L1 agents, an in­crease of 748 from a year ago. And there are 1,176 com­bi­na­tion stud­ies un­der­way, with a to­tal of 240 dif­fer­ent tar­gets.

— With a hand­ful of cell ther­a­pies ap­proved, CRI tracked 448 in pre­clin­i­cal de­vel­op­ment. Nine are in Phase III and 227 are in Phase II. The spike in cell ther­a­py work has pushed it in­to the lead among all 6 cat­e­gories tracked, well ahead of can­cer vac­cines and leav­ing on­colyt­ic virus­es be­hind — though that field is still grow­ing as well.

The US eas­i­ly re­mains the leader in the ge­og­ra­phy of I/O re­search, but Chi­na has been com­ing on strong as the num­ber 2 coun­try en­gaged in new re­search in­volv­ing I/O. And a num­ber of home grown PD-1/L1 drugs are near­ing ap­proval in Chi­na, with im­pli­ca­tions for the rest of the world.

Source: Can­cer Re­search In­sti­tute

Click on the im­age to see the full-sized ver­sion

Par­tic­u­lar­ly ex­cit­ing, says Vanes­sa Hub­bard-Lucey, di­rec­tor of the CRI Clin­i­cal Ac­cel­er­a­tor, is that “al­most all can­cer types are be­ing stud­ied with PD-1/L1 ther­a­pies in clin­i­cal tri­als, in­clud­ing many rare can­cers.”

But while all the num­bers con­tin­ue to steam ahead, there has been a sig­nif­i­cant de­cline in one key cat­e­go­ry: pa­tient re­cruit­ment has slowed 70% in 4 years, they say. And that un­der­scores a dra­mat­ic need to ex­pand the num­ber of pa­tients who can be re­cruit­ed for cur­rent and up­com­ing drug tri­als.

One of the rea­sons why I/O is so pop­u­lar is due to the mega-block­buster check­point suc­cess­es at Mer­ck and Bris­tol-My­ers Squibb. But while the lead­ers con­tin­ue to do well, every­one else look­ing to score gains of their own in a field like PD-1/L1 will be fac­ing a myr­i­ad of ri­vals be­ing ad­vanced for every con­ceiv­able tar­get. And a crush of com­peti­tors could well end up com­modi­tiz­ing the field, which is one rea­son why you’re see­ing so many com­bo stud­ies un­der­way. 

The lead­ers want to main­tain their lead, and the bio­phar­mas com­ing from be­hind want to find a way to break in with some­thing new.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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Oc­u­lar Ther­a­peu­tix ham­mered by a PhII fail­ure in dry eye dis­ease — shares tank

Ocular Therapeutix $OCUL has had its ups and downs in the 7 years since it went public. Friday was one of those down days.

The Bedford, MA-based biotech reported that its lead experimental eye drug, OTX-CSI (cyclosporine intracanalicular insert), failed a Phase II trial for dry eye disease. And the stock experienced one of its periodic meltdowns, dropping more than 30% ahead of the bell.

The therapy flat failed the primary endpoint: increased tear production at 12 weeks as measured by the Schirmer’s Test compared to the vehicle control group. And while investigators called out an improvement from baseline in “signs of dry eye disease as measured by total corneal fluorescein staining (CFS) and symptoms of dry eye disease as measured by the visual analogue scale (VAS) eye dryness in subjects treated with the OTX-CSI insert,” it wasn’t statistically significant.

Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.

Sanofi, Re­gen­eron etch out an­oth­er PhI­II vic­to­ry for Dupix­ent, eas­ing se­vere itch and clear­ing le­sions

Sanofi and Regeneron can boast of another inflammatory disease where Dupixent has proven effective.

The best-selling drug, which targets both IL-4 and IL-13, has delivered a clean sweep in a Phase III trial for prurigo nodularis, a chronic disease characterized by itch so intense that it can affect patients’ sleep and psychology. Thick skin lesions can cover most of the body.

On the primary endpoint, 37% of patients taking Dupixent saw a clinically meaningful reduction in itch compared to 22% of those on placebo (p=0.0216) at week 12. All secondary endpoints were also met, including clearance of skin lesions and improvement in quality of life.