FDA hands Mor­phoSys and In­cyte a quick OK on their po­ten­tial block­buster CAR-T al­ter­na­tive

Near­ly three years af­ter okay­ing the CAR-Ts Yescar­ta and Kym­ri­ah, the FDA has ap­proved a new CD19 ther­a­py.

Mor­phoSys’ Mon­ju­vi, or taf­a­sita­m­ab-cx­ix, was cleared Fri­day for use in re­frac­to­ry dif­fuse large B-cell lym­phoma (DBLCL). The ap­proval sets up both Mor­phoSys and their com­mer­cial part­ner In­cyte to com­pete with Gilead and No­var­tis in the ul­tra-com­pet­i­tive in­di­ca­tion, where sim­i­lar tri­al re­sults and far eas­i­er de­liv­ery could al­low them to cut a fair share of the mar­ket.

The first ap­proved in­di­ca­tion is in sec­ond-line DBLCL, for pa­tients in­el­i­gi­ble for au­tol­o­gous stem cell trans­plant. Mizuho’s Mara Gold­stein es­ti­mat­ed that mar­ket at around 6,000 US pa­tients and said the drug had “block­buster po­ten­tial,” but she not­ed those pa­tients have sev­er­al oth­er op­tions avail­able to them.

“The ini­tial mar­ket op­por­tu­ni­ty as a sec­ond-line treat­ment … is mean­ing­ful,” she wrote in a note to in­vestors, “though we are some­what cau­tious on the ramp of the drug giv­en the com­pet­i­tive land­scape for this in­di­ca­tion that in­cludes sev­en drug reg­i­mens as well as treat­ment with CAR-T ther­a­py.”

SVB Leerink’s Ge­of­frey Porges called the ap­proval a “best case sce­nario,” not­ing it had been un­clear whether the drug would be ap­proved for sec­ond-line or third-line ther­a­py. He es­ti­mat­ed a po­ten­tial pa­tient pop­u­la­tion around 12,000.

Both an­a­lysts sin­gled out Mon­ju­vi’s du­ra­tion in par­tic­u­lar. The 21.7 months it showed at the top line read­out is more than twice the 6 months to a year Roche’s an­ti­body-drug Po­livy, ap­proved last year, has shown.

“We be­lieve the CAR-T like ef­fi­ca­cy demon­strat­ed by tafa, as well as its fa­vor­able safe­ty pro­file should en­able broad adop­tion in the 2L set­ting,” Porges wrote in a note to in­vestors,  “and ex­pect the prod­uct to be pre­ferred over Roche’s CD79 ADC Po­livy.”

Si­mon Mo­roney

For­mer Mor­phoSys CEO Si­mon Mo­roney po­si­tioned Mon­ju­vi as an op­tion for pa­tients who can’t han­dle the in­tense bod­i­ly stress of high-dose chemother­a­py or stem cell trans­plant, or of CAR-T. In ad­di­tion to the cost­ly and lengthy process of ex­tract­ing, treat­ing and re-im­plant­i­ng T cells, CAR-T ther­a­pies al­so re­quire pa­tients to un­der­go “con­di­tion­ing” reg­i­mens of in­ten­sive chemother­a­py to clear out the bone mar­row and es­sen­tial­ly give a pock­et for the new cells to take hold.

By con­trast, Mon­ju­vi is an an­ti-CD19 an­ti­body that is giv­en in­tra­venous­ly and re­quires no con­di­tion­ing.

“Our pa­tients tend to be old­er — me­di­an age in the tri­al is 72,” Mo­roney told Med­C­i­ty News last June, re­fer­ring to par­tic­i­pants in their piv­otal Phase II study. “They have co­mor­bidi­ties and are not el­i­gi­ble for CAR-T.”

The FDA de­ci­sion is an ac­cel­er­at­ed ap­proval based on re­sults from that Phase II study. Topline re­sults re­leased last year showed a 55% over­all re­sponse rate and a 37% com­plete re­sponse rate. The lat­est da­ta, re­leased in May, showed a 59% re­sponse rate, a 39% com­plete re­sponse rate, and a me­di­an du­ra­tion of re­sponse that had risen to 34.6 months — near­ly 3 years. The com­plete re­sponse rates were in line with the ear­ly CAR-T tri­als, and the FDA grant­ed the drug pri­or­i­ty re­view.

Jean-Paul Kress

Both Mor­phoSys and In­cyte have staked a lot on Mon­ju­vi. Mor­phoSys raised $208 mil­lion in an IPO in 2018, fun­nel­ing much of that cash in­to build­ing out a US com­mer­cial op­er­a­tion in an­tic­i­pa­tion of their lead drug’s ap­proval. They tapped the US com­mer­cial lead for Mer­ck KGaA’s Baven­cio, David Trexler, to lead that ef­fort. And af­ter Mo­roney’s re­tire­ment, Jean-Paul Kress stepped in to lead a new stage for the com­pa­ny.

In­cyte, mean­while, spent $900 mil­lion ear­li­er this year to join with In­cyte on the com­mer­cial launch, hop­ing the CAR-T al­ter­na­tive could pour some oil in­to a sput­ter­ing R&D en­gine. Mizuho’s Gold­stein said the drug would help di­ver­si­fy In­cyte’s rev­enue base, but its over­all im­pact may be mut­ed.

“Mon­ju­vi may not have enough im­pact in the near term to al­ter the fun­da­men­tal pic­ture for the com­pa­ny,” she said of In­cyte.

Gold­stein al­so called the drug “val­i­da­tion” for Xen­cor’s plat­form. The Cal­i­for­nia biotech orig­i­nal­ly de­vel­oped the an­ti­body. The ap­proval trig­gered a $25 mil­lion mile­stone for them.

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.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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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.

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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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

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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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.