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.

M&A: a crit­i­cal dri­ver for sus­tain­able top-line growth in health­care

2021 saw a record $600B in healthcare M&A activity. In 2022, there is an anticipated slowdown in activity, however, M&A prospects remain strong in the medium to long-term. What are future growth drivers for the healthcare sector? Where might we see innovations that drive M&A? RBC’s Andrew Callaway, Global Head, Healthcare Investment Banking discusses with Vito Sperduto, Global Co-Head, M&A.

AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,300+ biopharma pros reading Endpoints daily — and it's free.

Abortion-rights protesters regroup and protest following Supreme Court's decision to overturn Roe v. Wade. (AP Photo/Gemunu Amarasinghe)

Fol­low­ing SCO­TUS de­ci­sion to over­turn abor­tion pro­tec­tions, AG Gar­land says states can't ban the abor­tion pill

Following the Supreme Court’s historic decision on Friday to overturn Americans’ constitutional right to an abortion after almost 50 years, Attorney General Merrick Garland sought to somewhat reassure women that states will not be able to ban the prescription drug sometimes used for abortions.

Following the decision, the New England Journal of Medicine also published an editorial strongly condemning the reversal, saying it “serves American families poorly, putting their health, safety, finances, and futures at risk.”

De­spite a slow start to the year for deals, PwC pre­dicts a flur­ry of ac­tiv­i­ty com­ing up

Despite whispers of a busy year for M&A, deal activity in the pharma space is actually down 30% on a semi-annualized basis, according to PwC’s latest report on deal activity. But don’t rule out larger deals in the second half of the year, the consultants said.

PwC pharmaceutical and life sciences consulting solutions leader Glenn Hunzinger expects to see Big Pharma companies picking up earlier stage companies to try and fill pipeline gaps ahead of a slew of big patent cliffs. Though a bear market continues to maul the biotech sector, Hunzinger said recent deals indicate that pharma companies are still paying above current trading prices.

Joe Wiley, Amryt Pharma CEO

Am­ryt Phar­ma sub­mits a for­mal dis­pute res­o­lu­tion to the FDA over re­ject­ed skin dis­ease drug

The story of Amryt Pharma’s candidate for the genetic skin condition epidermolysis bullosa, or EB, will soon enter another chapter.

After the Irish drugmaker’s candidate, dubbed Oleogel-S10 and marketed as Filsuvez, was handed a CRL earlier this year, the company announced in a press release that it plans to submit a formal dispute resolution request for the company’s NDA for Oleogel-S10.

Sen. Thom Tillis (R-NC) (J. Scott Applewhite/AP Images)

Phar­ma-friend­ly sen­a­tor calls on FDA for a third time to show patent pro­tec­tions should­n't be blamed for high drug prices

North Carolina Republican Sen. Thom Tillis made a name for himself in the 2020 election cycle as the darling of the pharma industry, accepting hundreds of thousands in campaign contributions, even from the likes of Pfizer CEO Albert Bourla.

Those contributions have led Tillis to attempt to re-write patent laws in pharma’s favor, a move which failed to gain steam in 2019, and request for a third time since January that the FDA should help stop “the false narrative that patent protections are to blame for high drug prices.”

EMA signs off on 3 drugs re­cent­ly re­ject­ed by FDA, in­clud­ing Bio­Mar­in's new he­mo­phil­ia gene ther­a­py

The EMA’s human medicines committee on Friday recommended three new drugs for approval or conditional approval, even as their US counterparts have rejected these three for various reasons.

In a major move, CHMP offered a thumbs-up to a conditional marketing authorization for the first gene therapy to treat severe hemophilia A, although the agency cautioned that it’s so far unknown how long the effects of infusion will last.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,300+ biopharma pros reading Endpoints daily — and it's free.

Joe Papa (Ryan Remiorz/The Canadian Press via AP, File)

Joe Pa­pa re­signs as chair of Bausch Health as bil­lion­aire John Paul­son takes over

Joe Papa, chair of Bausch Health, officially resigned on Thursday and the board appointed billionaire hedge fund manager John Paulson as the new chair, effective immediately.

The specialty pharma company sought to make clear that Papa’s abrupt departure “was not due to any dispute or disagreement with the Company, its management or the Board on any matter relating to the Company’s operations, policies or practices.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,300+ biopharma pros reading Endpoints daily — and it's free.

Yong Dai, Frontera Therapeutics CEO

Scoop: Lit­tle-known Or­biMed-backed biotech clos­es $160M round to start gene ther­a­py tri­al

Frontera Therapeutics, a China and US biotech, has closed a $160 million Series B and received regulatory clearance to test its first gene therapy stateside, Endpoints News has learned.

Led by the largest shareholder, OrbiMed, the biotech has secured $195 million total since its September 2019 founding, according to an email reviewed by Endpoints. The lead AAV gene therapy program is for an undisclosed rare eye disease, according to the source.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 144,300+ biopharma pros reading Endpoints daily — and it's free.