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.

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.

Pre-pandemic, the life sciences industry had settled into a pattern. The average drug took 12 years and $2.9 billion to bring to market, and it was an acceptable mode of operations, according to Nimita Limaye, Research Vice President for Life Sciences R&D Strategy and Technology at IDC.

COVID-19 changed that, and served as a proof-of-concept for how technology can truly help life sciences companies succeed and grow, Limaye said. She recently spoke about industry trends at Egnyte’s Life Sciences Summit 2022. You should watch the entire session, free and on-demand, but here’s a brief recap of why she’s urging life sciences companies to embrace digital transformation.

James Sabry’s BD team at Roche has a long track record in hunting the globe for new biotech deals. But they’ve never journeyed into China before to ink a worldwide development and commercialization pact with a China-based biotech on an experimental med.

As Max Gelman reported yesterday, Roche fronted a new alliance with China’s Jemincare with $60 million in cash and $590 million in milestones for worldwide commercial rights to an oral androgen receptor degrader. The deal itself is fairly typical of an early-stage alliance around a promising treatment. The Shanghai-based biotech is largely unknown outside China, but this is a classic high-risk, modest upfront pact that Roche routinely inks.

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Martin Landray knows what controversy in clinical drug development feels like, from first-hand experience.

Landray was the chief architect of RECOVERY, a study that pitted a variety of drugs against Covid-19. And he offered some landmark data that would help push dexamethasone out into broader use as a cheap treatment, while helping ice hydroxy’s reputation as a clear misfire.

“Lots of people told us we shouldn’t use it,” Landray says about dexamethasone and Covid-19. “It was dangerous. We shouldn’t even do a trial. They also cared about hydroxychloroquine and lots of people said we shouldn’t do a trial because it must be used. I’ve got the letters from both sets of people.”

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Biopharma companies that win new accelerated approvals typically have no financial incentive to complete their confirmatory trial because the price of the treatment doesn’t change once an accelerated approval converts to a full approval, researchers from Harvard, the University of Pennsylvania and the Brookings Institution wrote in a new Health Affairs study published yesterday.

Even as new cancer drugs approved under the AA pathway are launched at prices in excess of $100,000, companies often gain little from completing a quick confirmatory trial, and at least part of the problem, the researchers say, is that the FDA rarely withdraws a drug from the market because a company has failed to conduct a confirmatory trial or because the confirmatory trial showed no benefit.

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PI3K is a protein that is part of a pathway that regulates cell growth, survival and metabolism — earning it the inscription of master regulator for cancer. However, while a number of PI3K inhibitor drugs have been approved since 2014, the class as a whole has dwindled, as it has been plagued by toxicity issues in various blood cancers.

For example, the FDA hit Secura Bio’s PI3K inhibitor Copiktra, which earned accelerated approval in 2018, with an increased death warning in June following the results of its confirmatory Phase III trial. That warning came after a number of companies, including Secura, Gilead and Incyte, withdrew their accelerated approvals for their PI3K inhibitors after failing to complete confirmatory trials. The FDA now requires randomized trials to be conducted for PI3K inhibitors in blood cancers.

Roche’s Genentech is going high style next month for New York Fashion Week. The pharma is hosting its first-ever runway fashion show to raise disability visibility, featuring models from the spinal muscular atrophy (SMA) community.

“Double Take” will be held Sept. 8, the day before the official New York event begins, with models walking and rolling across the stage wearing stylish and functional adaptive clothing. Eleven people living with SMA and four advocates will show off the custom fashions created by Open Style Lab, a Brooklyn nonprofit and accessible clothing design collaborative.

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As Congress continues to mull whether and how to reform the FDA’s accelerated approval pathway, new research on the pathway continues to crop up, attempting to guide the way for new reforms.

Earlier this week, several prominent researchers from Harvard, UPenn and the Brookings Institution called for new financial incentives to encourage companies to finish the trials necessary to convert accelerated approvals to full approvals, or at least reform how companies are paid after winning an accelerated approval.

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It’s been just two days since Endo International filed for bankruptcy in an attempt to dig itself out of thousands of opioid lawsuits. Now one of its top sellers is in trouble.

A federal appeals court on Thursday affirmed a Delaware judge’s decision that Eagle Pharmaceuticals’ generic version of Endo’s vasopressin injection Vasostrict does not infringe on the company’s patents. Eagle’s version won approval back in December, and already, the generic and others like it have driven down Vasostrict sales.

Another Covid-19 vaccine will enter the fray as the EMA kicks off its conditional marketing authorization application for SK’s vaccine, dubbed Skycovion.

SK Chemicals GmbH submitted data to the EMA on how well the vaccine triggers the production of antibodies against the original strain of SARS-CoV-2, along with data on the safety and quality of the vaccine.

“The evaluation of Skycovion is one of the ongoing evaluations of data on Covid-19 vaccines. As the pandemic continues to evolve, it is important that the EU has a wide array of vaccines and treatments to enable the Member States to combat the pandemic effectively. EMA and its scientific committees are committed to ensuring a robust review of all data on COVID-19 vaccines and medicines,” the EMA said in a statement.

Bioscience & Technology Business Center The University of Kansas Lawrence, Kansas

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