In a bat­tered field, As­traZeneca's lu­pus drug clears piv­otal study — but can they get it ap­proved now?

A year af­ter As­traZeneca ad­mit­ted de­feat in a late-stage study test­ing its lu­pus drug an­i­frol­um­ab, the British drug­mak­er has cleared their sec­ond piv­otal tri­al, hit­ting the pri­ma­ry end­point and leav­ing their re­search team hope­ful that they have enough da­ta in hand to get an ap­proval.

Last year, an­i­frol­um­ab failed to meet the main goal of di­min­ish­ing dis­ease ac­tiv­i­ty in the 460-pa­tient TULIP 1 study, a 52-week tri­al that test­ed two dos­es of the drug ver­sus a place­bo. But in the 373-pa­tient TULIP II study, the high­er dose (300 mg) was com­pared to pa­tients giv­en a place­bo — and the study met the main goal of re­duc­ing dis­ease sever­i­ty.

Both tri­als mea­sured dis­ease ac­tiv­i­ty us­ing the British Isles Lu­pus As­sess­ment Group based Com­pos­ite Lu­pus As­sess­ment (BI­CLA) — which re­quires im­prove­ment in all or­gans with dis­ease ac­tiv­i­ty at base­line with no new flares — at week 52. In typ­i­cal fash­ion, the com­pa­ny is hold­ing the da­ta back for a sci­en­tif­ic con­fer­ence.

Reg­u­la­tors, though, won’t have to wait.

Usu­al­ly, a drug de­vel­op­er needs pos­i­tive da­ta from two piv­otal tri­als to se­cure ap­proval, but reg­u­la­tors have proved in­creas­ing­ly like­ly to over­look that stan­dard — par­tic­u­lar­ly if they’re up against a big chal­lenge like lu­pus. As­traZeneca’s Mene Pan­ga­los is look­ing to cap­i­tal­ize on that, in a state­ment on Thurs­day he said the com­pa­ny is ex­plor­ing path­ways to get an­i­frol­um­ab on the mar­ket.

The drug is a mon­o­clon­al an­ti­body en­gi­neered to thwart the ac­tiv­i­ty of all type I in­ter­fer­ons — cy­tokines in­volved in in­flam­ma­to­ry path­ways. Rough­ly 60% to 80% of adults with sys­temic lu­pus ery­the­mato­sus (SLE) car­ry in­creased type I in­ter­fer­on gene sig­na­ture, ac­cord­ing to As­traZeneca $AZN.

Lu­pus is a drug de­vel­op­er’s night­mare. In the last six decades, there has been one FDA ap­proval. In re­cent years, the field has re­sem­bled a grave­yard. Last Oc­to­ber, UCB and Bio­gen‘s $BI­IB an­ti-CD40L drug failed in a late-stage study, months af­ter Xen­cor $XN­CR and Sanofi’s $SNY Abl­ynx al­so con­ced­ed de­feat in their pro­grams.

Mean­while, there is cause for some cau­tious op­ti­mism. Some bi­o­log­ics that are ap­proved for oth­er au­toim­mune dis­ease are be­ing test­ed for use in lu­pus — in­clud­ing Eli Lil­ly’s $LLY Olu­mi­ant and J&J’s $JNJ Ste­lara. French biotech Neo­vacs is al­so in mid-stage de­vel­op­ment with a lu­pus vac­cine.

The on­ly bi­o­log­ic so far to win ap­proval for lu­pus is GSK’s $GSK Benlysta — which was cleared for adult use in 2011 and for rare cas­es of child­hood lu­pus this year. (GSK is in the midst of test­ing Benlysta in com­bi­na­tion with Roche’s rit­ux­imab in the hope the com­bi­na­tion will have a more po­tent ef­fect on the dis­ease ver­sus Benlysta monother­a­py.)

Apart from that, pa­tients are usu­al­ly giv­en NSAIDS, an­ti­malar­i­al drugs, cor­ti­cos­teroids and im­muno­sup­pres­sants to con­trol the symp­toms of the sys­temic au­toim­mune dis­ease, in which the body’s im­mune sys­tem launch­es an at­tack on its own tis­sues and or­gans. About 1.5 mil­lion Amer­i­cans and at least five mil­lion peo­ple glob­al­ly suf­fer from a form of lu­pus, es­ti­mates The Lu­pus Foun­da­tion of Amer­i­ca.

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.

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.

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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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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UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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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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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.