Matt Kapusta, uniQure CEO

UniQure halts high-dose treat­ments of Hunt­ing­ton's drug af­ter 3 pa­tients hos­pi­tal­ized — shares tank

UniQure has been work­ing on a gene ther­a­py for Hunt­ing­ton’s dis­ease for some time, and as the field has suf­fered through mul­ti­ple fail­ures, the com­pa­ny’s pro­gram has been set back.

The biotech an­nounced Mon­day morn­ing that back in Ju­ly, it had ob­served “sus­pect­ed, un­ex­pect­ed se­vere ad­verse re­ac­tions”, or SUSARs, in two pa­tients af­ter they were treat­ed with the “high­er dose” of a gene ther­a­py can­di­date, AMT-130, in a Eu­ro­pean Phase Ib/II clin­i­cal tri­al. A third pa­tient, who was treat­ed back in March in the US, had their side ef­fect deemed not re­lat­ed to the can­di­date, but it then was re­clas­si­fied as a se­vere ad­verse re­ac­tion af­ter re­view.

As a re­sult, it’s halt­ed dos­ing in the high dose co­hort. Ex­ecs said that the FDA and EMA had been no­ti­fied, but no spe­cif­ic di­a­logue has been made with those agen­cies yet.

Ex­ecs added in a con­fer­ence call Mon­day morn­ing they de­cid­ed to pause dos­ing af­ter con­sult­ing with the tri­al’s in­de­pen­dent da­ta safe­ty mon­i­tor­ing board (or DSMB).

“The DSMB does not view these events as a dose-lim­it­ing tox­i­c­i­ty and thus far in our in­ves­ti­ga­tion, we have not yet iden­ti­fied the root cause of these events,” uniQure ex­ecs said on the con­fer­ence call. They added that they have start­ed a safe­ty re­view that is ex­pect­ed to end in Q4 this year, and are con­sid­er­ing po­ten­tial risk mit­i­ga­tion plans over the next 2-3 months.

Shares for the gene ther­a­py biotech suf­fered af­ter the an­nounce­ment, with $QURE down more than 30% so far on the Nas­daq.

The pa­tients were hos­pi­tal­ized, with the US pa­tient suf­fer­ing se­vere headache and vom­it­ing. They were ad­mit­ted sev­en days af­ter un­der­go­ing a pro­ce­dure for the drug can­di­date, in which AAV is in­ject­ed in­to the stria­tum, a part of the brain linked to the basal gan­glia and Hunt­ing­ton’s dis­ease, via 3 holes over a mat­ter of sev­er­al hours. The pa­tient’s hos­pi­tal ad­mis­sion was orig­i­nal­ly de­ter­mined to be re­lat­ed to the pro­ce­dure, not the drug.

Af­ter be­ing treat­ed with anal­gesics and a di­ag­nos­tic lum­bar punc­ture, the pa­tient was dis­charged and then re­turned to the hos­pi­tal two days lat­er with a re­cur­ring headache, at­trib­uted to a leak of cere­brospinal flu­id af­ter that lum­bar punc­ture. The pa­tient was treat­ed with a blood patch (blood in­ject­ed in­to the spinal canal to patch the leak) and then has ful­ly re­cov­ered, ac­cord­ing to the biotech.

For the pa­tients in Eu­rope, it was a sim­i­lar sto­ry. Both of those pa­tients were ad­mit­ted to the hos­pi­tal around 12 days af­ter the pro­ce­dure, with the first pa­tient ex­pe­ri­enc­ing what the biotech de­scribed as “mo­tor and oth­er vi­tal symp­toms.” That pa­tient is still re­port­ed to have small deficits in flu­en­cy, mem­o­ry and at­ten­tion. The sec­ond Eu­ro­pean pa­tient re­port­ed vom­it­ing and raised in­tracra­nial pres­sure, be­ing ad­mit­ted around 12 days af­ter that pa­tient’s pro­ce­dure. Fol­low­ing ad­mis­sion, the pa­tient was found to have pa­pillede­ma, or op­tic disc swelling, but no ede­ma (aka swelling) in the stria­tum along the tracks of the holes drilled in­to the brain. That pa­tient re­ceived pro­phy­lac­tic an­tibi­otics and a lum­bar punc­ture to re­move 20 cc’s of cere­bral spinal flu­id — which led to symp­toms re­solv­ing and the pa­tient was then dis­charged.

Ri­car­do Dol­metsch

The com­pa­ny is keep­ing its re­search at the low­er dose of the gene ther­a­py on­go­ing, as CEO Matt Ka­pus­ta and head of R&D Ri­car­do Dol­metsch tell End­points News that no SAEs had been re­port­ed at that dose.

“The event re­al­ly is some­thing that hap­pens acute­ly, when you in­fuse some­body with a gene ther­a­py. We think it on­ly hap­pens at our high dose. Be­cause we nev­er saw it at a low dose,” Dol­metsch told End­points. The biotech’s R&D chief went on to say that so far, the com­pa­ny thinks that the most like­ly thing is some­thing unique to the pa­tients, but they don’t know for sure, yet.

Ka­pus­ta re­it­er­at­ed to End­points that this set­back would not im­pact the com­pa­ny’s planned da­ta dis­clo­sures, sched­uled for 2023.

So far, the biotech had en­rolled 36 pa­tients, 26 dosed with the can­di­date (low and high dose) and 10 on place­bo with up to 1-2 years of fol­low-up da­ta. All but 5 pa­tients in the high-dose co­hort have al­ready been dosed.

The hunt for a work­ing treat­ment for Hunt­ing­ton’s dis­ease has been a prover­bial mine­field. The ge­net­ic dis­ease where nerve cells be­gin to break down in peo­ple in their 30s and 40s has so far stumped many a biotech and phar­ma — such as Roche last year, when it stopped dos­ing of tomin­ersen in its Phase III, Io­n­is-part­nered tri­al af­ter the high dose made pa­tients’ dis­ease even worse.

Days af­ter that de­vel­op­ment, Wave Life Sci­ences al­so re­port­ed the fail­ure of its Hunt­ing­ton’s can­di­date, send­ing the com­pa­ny’s share price down 28% in the im­me­di­ate af­ter­math of the news.

Image courtesy of The Janssen Pharmaceutical Companies of Johnson & Johnson.

Pro­tect­ing the glob­al phar­ma­ceu­ti­cal in­no­va­tion ecosys­tem – what’s at stake?

We are living in a new era of healthcare that is rapidly advancing progress impacting patient outcomes and experiences. We’ve seen a remarkable pace of transformational innovation, applied research, and advanced clinical development over the last decade.

Despite this tremendous progress, there is much more work to be done, and patients are counting on us – now more than ever – to continue that momentum. At the heart of our industry is a focus on developing and delivering medicines for some of the world’s most challenging diseases, including those that have few or no effective treatments today.

Rich Horgan (R) with his late brother, Terry

Rich Hor­gan spear­head­ed a gene ther­a­py for his broth­er. The tri­al end­ed in tragedy, but the work con­tin­ues for more pa­tients

Rich Horgan’s quest to create a custom gene therapy for his brother, Terry, ended in tragedy. But Horgan doesn’t believe it’s the end of the story.

Terry, a 27-year-old patient with Duchenne muscular dystrophy, died last October just eight days after receiving the therapy in a clinical trial in which he was the only participant. The case raised questions about the safety of certain gene therapies and what would happen to other drug programs under a nonprofit that Horgan created, called Cure Rare Disease.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

Mi­rati’s drug sitra­va­tinib flops PhI­II in com­bo with Op­di­vo for cer­tain lung can­cer

Mirati Therapeutics’ path to a second drug approval will likely have to wait. The San Diego biotech company said Wednesday that its investigational lung cancer drug failed a Phase III trial testing it in combination with Bristol Myers Squibb’s Opdivo.

The drug, sitravatinib, and Opdivo weren’t better than the chemo drug docetaxel at keeping patients alive, Mirati said in a press release. The spectrum-selective kinase inhibitor missed the primary goal of overall survival in patients with second- or third-line advanced non-squamous, non-small cell lung cancer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

End­points 20(+2) un­der 40, 2023; Bio­phar­ma's high­est-paid CEOs; N-of-1 CRISPR sto­ry goes on af­ter tragedy; 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 will be off Monday in observance of Memorial Day — and when we get back, it will be a straight march to ASCO, BIO and more. Enjoy the (long) weekend!

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

Bio­phar­ma's 20 high­est-paid CEOs of 2022, each bring­ing in $20M+ pay­days

Even in a down year for much of the biopharma market, 20 CEOs brought in pay packages valued at more than $20 million, an Endpoints News analysis found.

Endpoints collected data on more than 350 CEO compensation packages, covering a wide range of pharma, biotech, and life sciences companies. All told, the 20 largest earners made over $725 million in 2022 — an average package of $36.4 million. Three brought in paydays over $50 million, and one CEO broke the $100 million mark.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

The 20(+2) un­der 40: Your guide to the next gen­er­a­tion of biotech lead­ers

This year’s list of 20 biotech leaders under the age of 40 includes a huge range of ambitions. Some of our honorees are planning to create the next big drug giant. Others are pushing the bounds of AI. One is working to revolutionize TB testing. All are compelling talents who are still young in age, but already far along in achievement.

And, as in years past, we went over. The 20 are actually 22 because of two double profiles that reflect how important teamwork is in the industry. As one of our honorees, Joe Illingworth of DJS Antibodies, told me in our interview, “It takes a village to raise a biotech.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

Teresa Bitetti, Takeda's president of the global oncology business unit

Take­da wins pri­or­i­ty re­view for $400M col­orec­tal can­cer drug, li­censed from Hutchmed in Jan­u­ary

Takeda and Hutchmed scored a priority review Thursday afternoon for a colorectal cancer drug, the companies announced.

The experimental drug in question is fruquintinib, previously approved in China in 2018 to treat metastatic colorectal cancer. Takeda and Hutchmed are aiming to bring fruquintinib to the US and other countries outside China in the same indication, and the FDA set its decision date for Nov. 30 of this year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

David Ricks, Eli Lilly CEO (Carolyn Kaster/AP Images)

Lil­ly gears up trio of PhI­II tri­als for its oral GLP-1 amid No­vo Nordisk, Pfiz­er com­pe­ti­tion

As Novo Nordisk and Pfizer disclose some data on their oral weight loss drugs in Phase III and II, respectively, Eli Lilly is beefing up its stance in the obesity field with three late-stage clinical trials of its next-generation GLP-1 agonist orforglipron.

The moves, disclosed in updates to the federal clinical trials database this week, put the Indianapolis drugmaker ahead of Pfizer, whose science chief has said the company will “cherry-pick” which of its mid-stage candidates to take deeper into the clinic after data late this year or early next.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 170,300+ biopharma pros reading Endpoints daily — and it's free.

Douglas Love, Annexon CEO

An­nex­on’s GA drug miss­es on pri­ma­ry goal but win on vi­su­al acu­ity will be fo­cus of planned late-stage tri­al

Annexon’s complement inhibitor didn’t prove better than sham at reducing lesion growth in a leading cause of blindness, but the biotech still plans to move forward on the back of secondary endpoints showing visual acuity preservation, which will “certainly” be the primary goal in a late-stage trial to be discussed shortly with the FDA, CEO Douglas Love told Endpoints News. 

The California biotech’s ANX007 was not statistically significant compared to pooled sham, the comparator, at 12 months in patients with geographic atrophy, per a Wednesday presentation. In every-month dosing, the GA lesion area changed about 6.2% from baseline (p=0.526) and 1.3% (p=0.896) in the every-other-month group. In a March note, Jefferies analyst Suji Jeong said a reduction of 20% to 30% would be “encouraging.”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.