Up­dat­ed: FDA adds warn­ing of 'larg­er ar­eas of bleed­ing' in brain to Bio­gen's Aduhelm la­bel

The FDA last week signed off on a safe­ty-re­lat­ed change to the la­bel of Bio­gen’s con­tro­ver­sial Alzheimer’s drug Aduhelm, which has bare­ly mus­tered any sales since its ap­proval be­cause pay­ers have re­fused to cov­er it.

The new la­bel makes clear that physi­cians should, “In­form pa­tients that events of in­trac­ere­bral he­m­or­rhage greater than 1 cm in di­am­e­ter have been re­port­ed in­fre­quent­ly in pa­tients tak­ing ADUHELM, and that the use of an­tithrom­bot­ic or throm­bolyt­ic med­ica­tions while tak­ing ADUHELM may in­crease the risk of bleed­ing in the brain.”

Brain bleed­ing and swelling are known side ef­fects of Aduhelm, and the FDA in­ves­ti­gat­ed a death of a 75-year-old woman who ex­pe­ri­enced both. Safe­ty da­ta from a study re­port­ing out in 2021 showed 41% of those in the piv­otal clin­i­cal tri­als of the Alzheimer’s drug ex­pe­ri­enced brain bleed­ing and swelling.

Mad­hav Tham­biset­ty, a neu­rol­o­gist at the NIH’s Na­tion­al In­sti­tute of Ag­ing, told End­points News via email:

While brain bleed­ing rep­re­sents a po­ten­tial­ly life-threat­en­ing acute com­pli­ca­tion re­lat­ed to ARIA [amy­loid-re­lat­ed imag­ing ab­nor­mal­i­ties], we do not ful­ly un­der­stand the long-term ef­fects of these changes ob­served on MRI scans. I am es­pe­cial­ly con­cerned about the re­la­tion­ship be­tween ARIA and ac­cel­er­at­ed loss of brain vol­ume seen with amy­loid low­er­ing an­ti­bod­ies (in­clud­ing ad­u­canum­ab, lecanemab and do­nanemab). The pub­li­ca­tions de­scrib­ing the re­sults of these clin­i­cal tri­als have not re­port­ed on the re­la­tion­ship be­tween the fre­quen­cy/sever­i­ty of ARIA and the loss of brain vol­ume. They have al­so not re­port­ed on the re­la­tion­ship be­tween APOE geno­type and loss of brain vol­ume.

The up­dat­ed la­bel for Aduhelm in­cludes the fol­low­ing (bold is up­dat­ed):

Some peo­ple may al­so have small spots of bleed­ing in or on the sur­face of the brain, and in­fre­quent­ly, larg­er ar­eas of bleed­ing in the brain can oc­cur. Most peo­ple with this type of swelling in the brain do not get symp­toms, how­ev­er some peo­ple may have symp­toms, such as: headache, nau­sea, con­fu­sion, dif­fi­cul­ty walk­ing, dizzi­ness, vi­sion changes, seizures.

More re­cent­ly, the FDA has ap­proved Bio­gen and part­ner Ei­sai’s sec­ond Alzheimer’s drug tar­get­ing amy­loid Leqem­bi, al­so known as lecanemab, which is still un­der an ac­cel­er­at­ed ap­proval, mean­ing CMS cov­er­age re­mains un­like­ly for now but is ex­pect­ed to soon win full ap­proval.

This is the sec­ond safe­ty-re­lat­ed up­date for Aduhelm’s la­bel, with the first com­ing in April 2022 to add seizures to the list of symp­toms above, among oth­er tweaks.

Bio­gen spokesper­son Al­li­son Parks told End­points via email that “this up­date isn’t based on any new safe­ty risks. Rather, this is FDA bring­ing the Aduhelm la­bel in line with the class of amy­loid be­ta-di­rect­ed an­ti­bod­ies, which at this stage in­cludes two treat­ments. As you’re aware, Leqem­bi was ap­proved in ear­ly Jan­u­ary and it in­clud­ed this lan­guage in its la­bel. But again, this isn’t in re­sponse to any new safe­ty risks.”

Ed­i­tor’s note: Ar­ti­cle up­dat­ed with com­ment from Bio­gen and NIA’s Mad­hav Tham­biset­ty.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Stéphane Bancel, Moderna CEO (AP Photo/Markus Schreiber)

Mod­er­na so­lid­i­fies deal with Kenya to build mR­NA man­u­fac­tur­ing fa­cil­i­ty

The mRNA player Moderna is further cementing its presence on the African continent.

Moderna announced on Thursday that it has finalized an agreement with Kenya’s government to partner up and bring an mRNA manufacturing facility to the east African nation. The new facility aims to manufacture up to 500 million doses of vaccines annually. Moderna also said the new facility will have the ability to spike its production capabilities to respond to public health emergencies on the continent or globally.

Ivana Magovčević-Liebisch, Vigil Neuroscience CEO

FDA lifts par­tial clin­i­cal hold on Vig­il Neu­ro­science's TREM2 an­ti­body, re­mov­ing dos­ing cap

When Vigil Neuroscience filed its IPO papers in late 2021, the biotech revealed that the FDA had just cleared its Phase I trial — but with a partial clinical hold that limited dosing to under a certain level.

More than a year later, the FDA has lifted the hold.

Vigil is now free to dose VGL101, an antibody targeting TREM2, at levels higher than 20 mg/kg in its ongoing and future clinical trials in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), an inherited condition that affects the brain and spinal cord.

Man­u­fac­tur­ing roundup: Catal­ent to pro­duce low-cost ver­sion of nalox­one; CSL opens R&D site

Catalent will be manufacturing a low-cost version of the opioid overdose treatment naloxone as part of a contract with Harm Reduction Therapeutics.

Catalent plans to manufacture the treatment at its facility in Morrisville, NC. No financial details on the deal were disclosed.

Harm Reduction was granted priority review status for the NDA on its spray last year. The company has been working on a naloxone product since 2017. It is anticipating approval in July of this year and a US launch in early 2024.

As­pen looks to re­bound in pro­duc­tion and rev­enue af­ter Covid-19

Last year, South African-based vaccine manufacturer Aspen Pharmacare was facing reports that it had not received a single order for its manufactured Covid-19 shots and that manufacturing lines were sitting idle. But now the vaccine producer is looking to turn things around.

Aspen’s disclosure of its financial results in March unveiled that manufacturing revenue had decreased by 12% to R 603 million ($33.8 million), which Lorraine Hill, Aspen Group’s COO, said is attributable to lower Covid vaccine sales.

Feng Zhang (Susan Walsh/AP Images)

In search of new way to de­liv­er gene ed­i­tors, CRISPR pi­o­neer turns to mol­e­c­u­lar sy­ringes

Bug bacteria are ruthless.

Some soil bacteria have evolved tiny, but deadly injection systems that attach to insect cells, perforate them and release toxins inside — killing a bug in just a few days’ time. Scientists, on the other hand, want to leverage that system to deliver medicines.

In a paper published Wednesday in Nature, MIT CRISPR researcher Feng Zhang and his lab describe how they engineered these syringes made by bacteria to deliver potential therapies like toxins that kill cancer cells and gene editors. With the help of an AI program, they developed syringes that can load proteins of their choice and selectively target human cells.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,900+ biopharma pros reading Endpoints daily — and it's free.

Ribbon cutting ceremony for Thermo Fisher's new cell therapy manufacturing site in San Francisco

Ther­mo Fish­er moves on cam­pus with new cell man­u­fac­tur­ing site in San Fran­cis­co

Thermo Fisher Scientific is putting down more roots in the Bay Area.

The manufacturer opened the doors to a new cell therapy manufacturing facility next to the University of California-San Francisco Medical Center’s Mission Bay campus and on the university’s campus.

UCSF and Thermo Fisher have had a partnership since 2021, with the new site focusing on manufacturing cell therapeutics for certain cancers, including glioblastoma and multiple myeloma. The new site plans to use Thermo Fisher’s expertise in manufacturing services to help UCSF accelerate the development of cell therapies and eventually get them into the clinic, said Dan Herring, the general manager of cell therapy services at Thermo Fisher, in an interview with Endpoints News.

Sulagna Bhattacharya, Nanoscope Therapeutics CEO

Nanoscope’s eye dis­ease gene ther­a­py shows mixed re­sults in PhII

Dallas-based biotech Nanoscope Therapeutics unveiled Phase II results on its gene therapy for a rare eye disease Thursday morning.

In the RESTORE trial, 18 patients with retinitis pigmentosa got a gene therapy called MCO-010 while nine got placebo. On a vision test called the MLYMT, the treatment group had a one-point greater change over one year in their score compared to the placebo group, the primary endpoint of the study. However, the 95% confidence interval was 0.0 to 3.0, meaning the result was not statistically significant. The p-value was not provided.

FDA grants full ap­proval to Keytru­da in tu­mor-ag­nos­tic set­ting; Can­del paus­es tri­al en­roll­ment

In a first, Merck has secured a full approval for Keytruda in a tumor agnostic setting — as a treatment for any unresectable or metastatic solid tumors that are classified as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

The FDA granted Keytruda accelerated approval in this indication in 2017, and GSK’s Jemperli followed suit in 2021. But now it’s converted to a full approval for Keytruda. Before prescribing, doctors would have to make sure patients carry this biomarker, using an FDA-approved test.