Zol­gens­ma did­n't cause an in­fant death, AveX­is ex­ecs say as they spot­light long-term da­ta

Be­fore the re­cent da­ta ma­nip­u­la­tion scan­dal en­gulfed No­var­tis’ star gene ther­a­py Zol­gens­ma, the death of an in­fant in one of their Phase III tri­als threat­ened to sound safe­ty alarms about the spinal mus­cu­lar at­ro­phy treat­ment. But sci­en­tists at the AveX­is sub­sidiary now say an in­ves­ti­ga­tion has cleared that par­tic­u­lar wor­ry.

Nes­tled in a lengthy pre­sen­ta­tion of up­beat da­ta, the up­date of­fers some much-need­ed val­i­da­tion for Zol­gens­ma as ex­ecs scram­ble to re­build their cred­i­bil­i­ty with both reg­u­la­tors and the gen­er­al pub­lic.

Out of the sev­er­al stud­ies tout­ed at the Eu­ro­pean Pae­di­atric Neu­rol­o­gy So­ci­ety Con­gress, there are a few key take­aways: Some of the ear­li­est pa­tients, as old as 5, are hit­ting de­vel­op­men­tal mile­stones in a long-term fol­low-up study; treat­ing in­fants be­fore they show any symp­toms of SMA has al­lowed them to grow up in a way they oth­er­wise nev­er would have; and there’s more ev­i­dence that the gene ther­a­py pre­vents symp­to­matic pa­tients’ from wors­en­ing.

While the au­top­sy re­port find­ings didn’t fea­ture up top, AveX­is ex­ecs did take the time to ad­dress them in a call with re­porters. Af­ter the British in­fant died in the STRIVE-EU study of a se­vere res­pi­ra­to­ry in­fec­tion fol­lowed by neu­ro­log­i­cal com­pli­ca­tions, the in­ves­ti­ga­tor thought the event might be re­lat­ed to treat­ment.

“We had been con­cerned about the po­ten­tial… that Zol­gens­ma might have been caus­ing brain in­flam­ma­tion,” AveX­is chief ex­ec­u­tive Dave Lennon said, as quot­ed by Reuters. “In this case, the orig­i­nal di­ag­no­sis, and that as­so­ci­a­tion, hasn’t held true.”

Al­though Zol­gens­ma might have been re­spon­si­ble for oth­er known side ef­fects such as el­e­vat­ed en­zymes in the liv­er, low platelets and low blood pres­sure, their in­ves­ti­ga­tion found no ev­i­dence of treat­ment-re­lat­ed brain dam­age. The con­clu­sion: SMA Type 1 was the un­der­ly­ing cause for the in­fec­tion, which in turn de­prived the brain of oxy­gen and trig­gered hy­pox­ic-is­chemic brain dam­age.

Mean­while, the rest of the re­sults demon­strate the “life-chang­ing im­pact Zol­gens­ma can have on chil­dren with SMA Type 1” for fam­i­lies who nev­er ex­pect­ed their chil­dren to crawl, sit or walk, said CMO Ol­ga San­ti­a­go in a state­ment.

START, which start­ed out as a 13-pa­tient safe­ty study, is now track­ing 10 of those pa­tients with a mean age of 4.2 years for whom treat­ment was on av­er­age 3.9 years ago. All are alive and the ma­jor­i­ty (sev­en) is not re­ceiv­ing Spin­raza, Bio­gen’s SMA main­te­nance ther­a­py. Six of them do not re­quire dai­ly res­pi­ra­to­ry sup­port, and at least two are able to stand with as­sis­tance in ad­di­tion to two oth­ers who were re­port­ed to be walk­ing in­de­pen­dent­ly.

Se­ri­ous ad­verse events were re­port­ed, af­fect­ing six out of the 13 orig­i­nal pa­tients, but AveX­is main­tained that noth­ing was new.

In the SPR1NT study, pa­tients were treat­ed much younger — less than 6 weeks — as they tend to be di­ag­nosed at birth. It’s on­ly been a few months since the 23 pa­tients were dosed, but among those with two copies of SMN2, six out of 10 were able to sit with­out sup­port for at least 30 sec­onds — a co-pri­ma­ry end­point. Over­all, of the 22 be­ing eval­u­at­ed, all were alive with­out the help of per­ma­nent ven­ti­la­tion.

The fi­nal da­ta cut won’t be tak­en un­til two years af­ter treat­ment, yet these in­ter­im re­sults show why it’s crit­i­cal to di­ag­nose SMA and in­ter­vene as ear­ly as pos­si­ble, ac­cord­ing to San­ti­a­go.

A sep­a­rate Phase III glob­al tri­al dubbed STR1VE is al­so watch­ing for the 30-sec­ond sit­ting as a co-pri­ma­ry end­point. There, so far, 50% of pa­tients in the US tri­al and 6% in the EU tri­al has hit that goal — some­thing that ba­bies with SMA Type 1 would nev­er be able to do, AveX­is em­pha­sized.

The oth­er co-pri­ma­ry is event-free sur­vival as mea­sured by avoid­ance of death or per­ma­nent ven­ti­la­tion. The tri­al is sched­uled to wrap lat­er this year.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Dave Lennon, former president of Novartis Gene Therapies

Zol­gens­ma patent spat brews be­tween No­var­tis and Re­genxbio as top No­var­tis gene ther­a­py ex­ec de­parts

Regenxbio, a small licensor of gene therapy viral vectors spun out from the University of Pennsylvania, is now finding itself in the middle of some major league patent fights.

In addition to a patent suit with Sarepta Therapeutics from last September, Novartis, is now trying to push its smaller partner out of the way. The Swiss biopharma licensed Regenxbio’s AAV9 vector for its $2.1 million spinal muscular atrophy therapy Zolgensma.

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Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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FDA hands ac­cel­er­at­ed nod to Seagen, Gen­mab's so­lo ADC in cer­vi­cal can­cer, but com­bo stud­ies look even more promis­ing

Biopharma’s resident antibody-drug conjugate expert Seagen has scored a clutch of oncology approvals in recent years, finding gold in what are known as “third-gen” ADCs. Now, another of their partnered conjugates is ready for prime time.

The FDA on Monday handed an accelerated approval to Seagen and Genmab’s Tivdak (tisotumab vedotin-tftv, or “TV”) in second-line patients with recurrent or metastatic cervical cancer who previously progressed after chemotherapy rather than PD-(L)1 systemic therapy, the companies said in a release.

Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.

As­traZeneca, Dai­ichi Sanky­o's ADC En­her­tu blows away Roche's Kad­cy­la in sec­ond-line ad­vanced breast can­cer

AstraZeneca and Japanese drugmaker Daiichi Sankyo think they’ve struck gold with their next-gen ADC drug Enhertu, which has shown some striking data in late-stage breast cancer trials and early solid tumor tests. Getting into earlier patients is now the goal, starting with Enhertu’s complete walkover of a Roche drug in second-line breast cancer revealed Saturday.

Enhertu cut the risk of disease progression or death by a whopping 72% (p=<0.0001) compared with Roche’s ADC Kadcyla in second-line unresectable and/or metastatic HER2-positive breast cancer patients who had previously undergone treatment with a Herceptin-chemo combo, according to interim data from the Phase III DESTINY-Breast03 head-to-head study presented at this weekend’s #ESMO21.

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The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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