Io­n­is, Akcea team face some tough ques­tions on safe­ty as FDA in­sid­ers pon­der risks linked to volane­sors­en

Re­searchers for Io­n­is’ $IONS ma­jor­i­ty-owned spin­out Akcea will have plen­ty of per­suad­ing to do this week if they ever ex­pect to get their drug volane­sors­en on the mar­ket.

The FDA in­ter­nal re­view came out to­day, re­flect­ing the same deep con­cerns that an­a­lysts have ex­pressed about the safe­ty of a drug that has been linked with re­peat­ed in­stances of sud­den and dan­ger­ous drops in platelet counts. Platelets are need­ed to trig­ger the clot­ting that stops bleed­ing.

Akcea’s shares $AK­CA im­me­di­ate­ly tum­bled 15% on the neg­a­tive tone of the in­ter­nal re­view.

James Smith

In a memo to the ad­vi­so­ry com­mit­tee meet­ing on Thurs­day, James Smith, the deputy di­rec­tor of the Di­vi­sion of Me­tab­o­lism and En­docrinol­o­gy Prod­ucts, spot­light­ed a gen­er­al agree­ment that the drug has a clear­ly pos­i­tive ef­fect on reg­u­lat­ing plas­ma triglyc­eride for pa­tients with rare cas­es of fa­mil­ial chy­lomi­crone­mia syn­drome. That’s a sur­ro­gate end­point for the dis­ease.

But is the ben­e­fit re­al­ly worth the risk of bleed­ing? That’s the big ques­tion that the de­vel­op­ers face this week. Reg­u­la­tors are al­so some­what per­plexed by Akcea’s wish to switch the dos­ing reg­i­men and their platelet mon­i­tor­ing strat­e­gy to some­thing that was nev­er test­ed in the clin­i­cal tri­als. 

From Smith’s note:

Al­though the re­views high­light sev­er­al safe­ty/tol­er­a­bil­i­ty is­sues, the pri­ma­ry fo­cus for both the ap­pli­cant and the re­view­ers has been the risk of throm­bo­cy­tope­nia (low blood platelet counts) and re­sult­ing po­ten­tial for se­ri­ous bleed­ing….(S)ome pa­tients can ex­hib­it a rapid and un­pre­dictable re­duc­tion in platelets to ex­treme­ly low lev­els. In CS6, no pa­tients as­signed to place­bo had a platelet count fall be­low 100,000/uL com­pared with 18 (55%) of 33 pa­tients as­signed to volane­sors­en…Switch­ing to bi­week­ly dos­ing and/or dose in­ter­rup­tions have not al­ways led to a suf­fi­cient­ly time­ly re­cov­ery of platelet count; some pa­tients have re­quired treat­ment with pred­nisone, hos­pi­tal­iza­tion, and/or ad­min­is­tra­tion of IVIG. To date, se­ri­ous bleed­ing events have not been ob­served in this rel­a­tive­ly lim­it­ed safe­ty data­base, but the re­view­ers high­light a high­er risk of non-se­ri­ous bleed­ing-re­lat­ed ad­verse events with volane­sors­en (e.g., epis­taxis, pe­techi­ae). Some of these events oc­curred at platelet lev­els where spon­ta­neous bleed­ing would be un­ex­pect­ed, sug­gest­ing the pos­si­bil­i­ty of an ab­nor­mal­i­ty of platelet func­tion as well as an ef­fect on platelet count.

Io­n­is re­port­ed a lit­tle more that a year ago that it had achieved its ef­fi­ca­cy end­point in Phase III. But five pa­tients were forced out of the tri­al due to a threat­en­ing de­cline in platelet counts. Grade 4 throm­bo­cy­tope­nia oc­curred in three pa­tients, which end­ed af­ter they stopped dos­ing. There were no with­drawals due to platelet counts af­ter the com­pa­ny be­gan mon­i­tor­ing the side ef­fect.

If they do get an ap­proval, says Smith, it will have to come with a REMS. But right now, that looks like the best case sce­nario.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Kristen Hege, Bristol Myers Squibb SVP, early clinical development, oncology/hematology and cell therapy (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: Bris­tol My­er­s' Kris­ten Hege on cell ther­a­py, can­cer pa­tients and men­tor­ing the next gen­er­a­tion

Kristen Hege leads Bristol Myers Squibb’s early oncology discovery program carrying on from the same work at Celgene, which was acquired by BMS in 2019. She’s known for her early work in CAR-T, having pioneered the first CAR-T cell trial for solid tumors more than 25 years ago.

However, the eminent physician-scientist is more than just a drug developer mastermind. She’s also a practicing physician, mother to two young women, an avid backpacker and intersecting all those interests — a champion of young women and people of color in STEM and life sciences.

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Eisai and METAvivor plan to debut the latest 'This is MBC' campaign at the San Antonio Breast Cancer Symposium (SABCS).

Ei­sai re-ups metasta­t­ic breast can­cer aware­ness cam­paign with strik­ing pa­tient pho­tographs

Eisai is debuting the newest ads in its long-running “This is MBC” campaign this week. In what’s become an annual tradition, Eisai and metastatic breast cancer advocacy partner METAvivor will show the striking photographs of people living with metastatic breast cancer first at the San Antonio Breast Cancer Symposium (SABCS).

The new “Imagine” campaign features 12 patients photographed around waterfalls to symbolize that same kind of sudden drop into a pool that MBC causes in a person’s life, said Beth Fairchild, co-founder of #CancerCulture who was the president of METAvivor six years ago when the campaign began. Fairchild, who is living with MBC, has helped create all of the annual “This is MBC” campaigns.

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Pfiz­er and BioN­Tech look to toss Mod­er­na patent suit, call­ing claims 'unen­force­able'

Pfizer and BioNTech took a swing at Moderna’s Covid-19 patent claims in Massachusetts federal court on Monday, calling them “invalid,” “overbroad” and “unenforceable.”

The defendants also filed counterclaims against the Cambridge, MA-based biotech, seeking a dismissal of the case, recovery of court fees and an official judgment invalidating Moderna’s claims.

Moderna sued Pfizer and BioNTech back in August, alleging that the partners’ Covid-19 vaccine Comirnaty copied parts of Moderna’s vaccine technology patented before the pandemic, when it was developing an mRNA vaccine for MERS, another respiratory illness.

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Glen­mark hit with warn­ing let­ter over pro­ce­dures, qual­i­ty con­trol is­sues at In­dia man­u­fac­tur­ing plant

The generics producer Glenmark Pharmaceuticals has been handed a warning letter by US regulators.

The letter, which was sent to the manufacturer on Nov. 22, noted issues from an inspection over the summer at Glenmark’s facility in the town of Colvale, India, in the state of Goa.

According to the letter, the FDA found that Glenmark’s investigation of rejected batches of drugs “failed to extend to other batches, dosage strengths, and drug products.” The warning letter also noted that the site had failed to establish “adequate written procedures” for production and process control to ensure drugs have the correct strength, quality and purity.

Klick Health is lighting the way, literally, this holiday season to encourage connection for lonely seniors in long-term care facilities.

Klick Health an­nu­al hol­i­day spot­light se­nior lone­li­ness and the pow­er of con­nec­tion

Every year Klick Health leans into a cause for the holidays, and this year it’s highlighting the sometimes lonely season for seniors. So Klicksters, as employees call themselves, decided to brighten one nursing home community in hopes of inspiring others to do the same.

Klick literally lit up the Tony Stacey Centre for Veterans Care, a long-term care home in Toronto where 75% of residents receive no visitors during the holiday season. The agency brought staff and family along with lighting crews and musicians for a “Light the Way” event, creating a video of the experience debuting on Tuesday.

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Sum­i­to­vant sub­sidiaries En­zy­vant and Al­ta­vant merge in­to com­bined com­pa­ny

Two Sumitovant Biopharma entities are merging under one name, effective immediately.

Enzyvant Therapeutics and Altavant Sciences announced they have merged to form a singular entity focused on developing therapies for patients with rare diseases. The combined company will keep the name Enzyvant and along with clinical development will eventually include in-house manufacturing.

Bill Symonds, the current CEO of both Altavant and Enzyvant, is now CEO of the merged company.

Gossamer Bio CEO Faheem Hasnain at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Gos­samer’s Fa­heem Has­nain de­fends a round of pos­i­tive PAH da­ta as a clear win. But can these PhII re­sults stand up to scruti­ny?

Gossamer Bio $GOSS posted a statistically significant improvement for its primary endpoint in the key Phase II TORREY trial for lead drug seralutinib on Tuesday morning. But CEO Faheem Hasnain has some explaining to do on the important secondary of the crucial six-minute walk distance test — which will be the primary endpoint in Phase III — as the data on both endpoints fell short of expectations, missing one analyst’s bar on even modest success.

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Eu­ro­pean Com­mis­sion lays ground­work to un­wind Il­lu­mi­na's $7B+ Grail merg­er

The European Commission has recommended steps that — though not yet final — would require Illumina to “swiftly” unwind its controversial $7.1 billion Grail buyout.

The Commission delivered a “statement of objections” on Monday, detailing the process Illumina would need to take in divesting Grail, its blood testing spinout launched in 2016. Illumina re-acquired Grail back in August, despite criticism from both the FTC and EU.