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.

Un­pack­ing the Aduhelm de­ci­sion, Ver­tex's half full glass, a $525M J&J breakup, 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.

By now you have surely read about the FDA’s controversial approval of Biogen’s Alzheimer’s drug and all its reverberations. But I’d still recommend checking out the meaty recap below to make sure you didn’t miss all the angles that the Endpoints team has covered. If you’d rather look ahead, look no further than our three-day virtual panels next week at BIO, where we will discuss what the new normal means for every part of the industry.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

What does a clear ma­jor­i­ty of the bio­phar­ma in­dus­try think of the FDA ap­proval of ad­u­canum­ab? 'Hor­ri­fy­ing' 'Dan­ger­ous' 'Con­fus­ing' 'Dis­as­ter'

Over the years, we’ve become used to seeing a consensus emerge early in our industry polls at Endpoints News. And when we took the pulse of drug hunters on the heels of a controversial FDA approval for aducanumab this week, it became immediately apparent that the vast majority of our readers — heavily concentrated among biopharma staffers and execs — were incensed by what they had just witnessed.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Aaron Kesselheim (Scott Eisen/AP Images for AIDS Healthcare Foundation)

Har­vard’s Aaron Kessel­heim re­signs from ex­pert pan­el in wake of ad­u­canum­ab OK, blast­ing FDA for ‘worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry'

A third member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has resigned in the wake of Biogen’s controversial Aduhelm approval, slamming the agency as he left and further deepening the controversy surrounding the decision.

Harvard University professor Aaron Kesselheim quit in protest Thursday afternoon, calling the Aduhelm OK “probably the worst drug approval decision in recent U.S. history.” Kesselheim follows both Joel Perlmutter, a neurologist from Washington University in St. Louis, and David Knopman, a neurologist from the Mayo Clinic, out the door.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Paul Hudson, Sanofi CEO (Eric Piermont/AFP via Getty Images)

Months af­ter FDA re­jec­tion, Sanofi touts piv­otal win for rare dis­ease drug su­tim­limab as it preps to re­file

One of the pillar drugs of Sanofi’s $11.6 billion pickup of Bioverativ hit a big setback late last year when the FDA sent its application for approval back. Now, as Sanofi gears up to resubmit the drug for review, the drugmaker is touting pivotal data it hopes will help take it over the finish line.

Sanofi’s sutimlimab nailed all three of its primary endpoints in its Phase III CADENZA study for patients with cold agglutinin disease, a rare disorder that can cause severe anemia, without a recent history of blood transfusion, the French drugmaker said Friday. The topline results will be presented at this weekend’s virtual EHA meeting.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Janet Woodcock, acting FDA commissioner, at Thursday's Senate Appropriations hearing (Bill Clark/CQ Roll Call via AP Images)

Sen­a­tors lam­bast new Alzheimer’s drug’s price but give Janet Wood­cock a free pass on the ap­proval de­ci­sion

Senate Finance Democrats took aim at Biogen’s pricey new Alzheimer’s drug on Thursday, but members on both sides of the aisle at a separate appropriations hearing didn’t question acting FDA commissioner Janet Woodcock on the approval.

“I was appalled that Biogen priced their Alzheimer’s drug approved by the FDA at $56,000 per year — I’m not going to debate whether this is effective or not, but it’s double the household median income for Michiganders over the age of 65,” Sen. Debbie Stabenow (D-MI) said at the finance hearing.

Reshma Kewalramani, Vertex CEO (BIO via YouTube)

UP­DAT­ED: Ver­tex strikes out on its lat­est big shot at a rare ge­net­ic dis­ease. But they're go­ing to keep on swing­ing

It’s been several months since Vertex culled one of its small molecules for alpha-1 antitrypsin deficiency (AATD), taking a big hit after evidence of liver damage surfaced in a key Phase II trial. Now we learned that the company has whiffed on its second shot, and there’s nothing left in the clinic to treat the rare genetic disease — but that won’t stop it from trying.

Despite avoiding the safety issues that plagued the last candidate, Vertex $VRTX is taking the axe to VX-864 after Phase II results revealed the magnitude of the drug’s response is “unlikely to translate into substantial clinical benefit.” As a result of the news, the company’s stock fell 12.5% after hours.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

FDA au­tho­rizes about 10M J&J vac­cine dos­es, trash­es 60M more from trou­bled Emer­gent plant

The FDA on Friday released about 10 million doses of J&J’s vaccine for use, and disposed of another 60 million doses that were manufactured at the now-shuttered Emergent BioSolutions facility in Baltimore where cross-contamination occurred.

The agency said it’s not yet ready to allow the Emergent plant to be included in the J&J EUA, but that may occur soon. FDA came to the decision to authorize some of the doses after reviewing facility records and quality testing results.

Bris­tol My­er­s' CAR-T Breyanzi busts out a win in ear­li­er-line lym­phoma, po­ten­tial­ly crack­ing open an ex­pand­ed mar­ket

Despite being third to the field in B cell lymphoma, Bristol Myers Squibb has repeatedly argued its CAR-T Breyanzi could have the juice to overtake its older competitors. Going into earlier lines of therapy may be the golden ticket on that front, and now Breyanzi has a late-stage win to back up that effort.

Bristol Myers’s Breyanzi beat out physicians’-choice salvage therapy followed by high-dose chemo and a stem cell transplant — what the drugmaker called a “gold standard treatment” — in second-line patients with relapsed or refractory large B cell lymphoma, according to topline data from the Phase III TRANSFORM study released Thursday.