Does an im­proved safe­ty pro­file strength­en Al­ler­gan's case for a wet AMD chal­lenge to Lu­cen­tis?

Al­ler­gan has chalked up some flat­ter­ing safe­ty da­ta for abic­i­par as it re­fines the eye drug’s man­u­fac­tur­ing process­es in prepa­ra­tion of an im­pend­ing BLA fil­ing. But whether or how much that mat­ters is still up for de­bate.

In an open-la­bel, sin­gle-arm study, in­ves­ti­ga­tors re­port­ed that the in­ci­dence of in­traoc­u­lar in­flam­ma­tion was 8.9% — low­er than the rate ob­served in pri­or Phase III stud­ies, which hov­ered around 15%. The MAPLE tri­al re­cruit­ed 123 age-re­lat­ed neo­vas­cu­lar mac­u­lar de­gen­er­a­tion (or wet AMD) pa­tients and ad­min­is­tered the in­jec­tion five times over 28 weeks.

David Nichol­son, Al­ler­gan

“The re­sults of this open-la­bel study en­abled us to as­sess im­prove­ments to the man­u­fac­tur­ing process for abic­i­par. The safe­ty pro­file demon­strat­ed in MAPLE gives us con­fi­dence to pro­ceed and scale up man­u­fac­tur­ing,” said David Nichol­son, chief re­search and de­vel­op­ment of­fi­cer. “We plan to sub­mit the abic­i­par BLA and con­tin­ue to pur­sue man­u­fac­tur­ing process im­prove­ments as we de­vel­op larg­er scale stud­ies in ad­di­tion­al dis­ease states, such as di­a­bet­ic mac­u­lar ede­ma.”

Any lit­tle im­prove­ment could be cru­cial as Al­ler­gan and its al­lies at Mol­e­c­u­lar Part­ners go up against the en­trenched mar­ket lead­ers, Re­gen­eron’s Eylea and No­var­tis’ Lu­cen­tis, both ap­proved for mul­ti­ple in­di­ca­tions oth­er than wet AMD, which is far less com­mon but much more se­vere than dry AMD. And the two gi­ants are each ad­vanc­ing fol­low-on ef­forts of their own.

The new in­flam­ma­tion rates, though, might still do lit­tle to change in­vestors’ skep­ti­cal views on the com­mer­cial prospect, said Umer Raf­fat of Ever­core ISI.

Raf­fat notes that se­vere in­flam­ma­tion reg­is­tered at 1.6% in the MAPLE tri­al, com­pared to 3.2% to 3.7% ob­served in pre­vi­ous Phase III stud­ies.

AGN feels strong­ly that it’s re­al­ly just the se­vere in­flam­ma­tion that mat­ters … and that it’s now at a well con­trolled rate (<2%) … and that mild in­flam­ma­tion is asymp­to­matic.

If we agree with AGN’s log­ic, there is an impt piece of da­ta that hasn’t been dis­closed about MAPLE: the rate of mod­er­ate in­flam­ma­tion. (we know mild+mod+se­vere = 8.9% … and se­vere is 1.6% … but what is mod­er­ate? if we go by Ph 3 re­sults, mod­er­ate could be half of this 8.9% … but un­clear if that ac­tu­al­ly hap­pened in MAPLE al­so).

To put it blunt­ly: “It will be a ‘show-me’ sto­ry at launch.”

An­a­lysts for SVB Leerink was even more doubt­ful, not­ing:

Re­port­ed in­ci­dence of in­traoc­u­lar in­flam­ma­tion (IOI) was 8.9% in the MAPLE study, which was low­er than pri­or Phase 3 stud­ies (>15% af­ter 1 year of treat­ment), but still sig­nif­i­cant­ly high­er than the rate ob­served in No­var­tis’ (NVS, NR) Lu­cen­tis and Re­gen­eron’s (REGN, OP) Eylea, which we think would lim­it its suc­cess to be a re­al play­er in the space.

In­vestors seem to be sit­ting this one out for now. Al­ler­gan $AGN shares are slight­ly in the red this morn­ing, dip­ping 0.33%, or $0.5, pre-mar­ket.

The duo has pre­vi­ous­ly tout­ed Phase III da­ta sug­gest­ing abic­i­par is non-in­fe­ri­or to Lu­cen­tis on both test­ed sched­ules, though the in­ci­dence of in­traoc­u­lar in­flam­ma­tion re­mained a sore point giv­en that less than 1% of the pa­tients on the ri­val drug ex­pe­ri­enced it.

Where Al­ler­gan is hop­ing to stand out is the dos­ing reg­i­men, a fixed 12-week reg­i­men that could “great­ly re­duce the treat­ment bur­den” ac­cord­ing to Cleve­land Clin­ic Cole Eye In­sti­tute’s Pe­ter Kaiser. That’s thanks to Mol­e­c­u­lar Part­ners’ DARPin tech­nol­o­gy, which it says has high­er sta­bil­i­ty and po­ten­cy than mon­o­clon­al an­ti­bod­ies.

A BLA is still slat­ed for the next two months, Al­ler­gan and Mol­e­c­u­lar Part­ners say, as pre­vi­ous­ly re­port­ed.

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.

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 is 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 is 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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David Lockhart, ReCode Therapeutics CEO

Pfiz­er throws its weight be­hind LNP play­er eye­ing mR­NA treat­ments for CF, PCD

David Lockhart did not see the meteoric rise of messenger RNA and lipid nanoparticles coming.

Thanks to the worldwide fight against Covid-19, mRNA — the genetic code that can be engineered to turn the body into a mini protein factory — and LNPs, those tiny bubbles of fat carrying those instructions, have found their way into hundreds of millions of people. Within the biotech world, pioneers like Alnylam and Intellia have demonstrated just how versatile LNPs can be as a delivery vehicle for anything from siRNA to CRISPR/Cas9.

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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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Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

The pharma giant noted on clinicaltrials.gov that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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Leen Kawas (L) has resigned as CEO of Athira and will be replaced by COO Mark Litton

Ex­clu­sive: Athi­ra CEO Leen Kawas re­signs af­ter in­ves­ti­ga­tion finds she ma­nip­u­lat­ed da­ta

Leen Kawas, CEO and founder of the Alzheimer’s upstart Athira Pharma, has resigned after an internal investigation found she altered images in her doctoral thesis and four other papers that were foundational to establishing the company.

Mark Litton, the company’s COO since June 2019 and a longtime biotech executive, has been named full-time CEO. Kawas, meanwhile, will no longer have ties to the company except for owning a few hundred thousand shares.

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Sen. Richard Durbin (D-IL, foreground) and Sen. Richard Blumenthal (D-CT) (Patrick Semansky/AP Images)

Sen­a­tors back FDA's plan to re­quire manda­to­ry pre­scriber ed­u­ca­tion for opi­oids

Three Senate Democrats are backing an FDA plan to require mandatory prescriber education for opioids as overdose deaths have risen sharply over the past decade, with almost 97,000 American opioid-related overdose deaths in the past year alone.

While acknowledging a decline in overall opioid analgesic dispensing in recent years, the FDA said it’s reconsidering the need for mandatory prescriber training through a REMS given the current situation with overdoses, and is seeking input on the aspects of the opioid crisis that mandatory training could potentially mitigate.

Bris­tol My­ers pledges to sell its Ac­celeron shares as ac­tivist in­vestors cir­cle Mer­ck­'s $11.5B buy­out — re­port

Just as Avoro Capital’s campaign to derail Merck’s proposed $11.5 billion buyout of Acceleron gains steam, Bristol Myers Squibb is leaning in with some hefty counterweight.

The pharma giant is planning to tender its Acceleron shares, Bloomberg reported, which add up to a sizable 11.5% stake. Based on the offer price, the sale would net Bristol Myers around $1.3 billion.

To complete its deal, Merck needs a majority of shareholders to agree to sell their shares.