Sarep­ta touts clean da­ta for com­mer­cial grade Duchenne gene ther­a­py, clear­ing key hur­dle to PhI­II

Af­ter a tri­al flop and an un­ex­pect­ed de­tour, Sarep­ta says its gene ther­a­py for Duchenne mus­cu­lar dy­s­tro­phy looks ready to get back on the Phase III track.

Doug In­gram

A re­view of pre­lim­i­nary safe­ty and ex­pres­sion da­ta from 11 pa­tients sug­gests that the ma­te­r­i­al man­u­fac­tured with their up­dat­ed com­mer­cial process spurred con­sis­tent pro­duc­tion of dy­s­trophin, the biotech re­port­ed, while main­tain­ing a clean side ef­fect pro­file. The study, SRP-9001-103, was the first to test Sarep­ta’s com­mer­cial grade process in pa­tients.

The plan is to take these re­sults to the FDA for a meet­ing be­fore the end of June, and kick­start its much-an­tic­i­pat­ed Phase III soon af­ter.

“We feel very very good where we are,” CEO Doug In­gram said on an in­vestor call.

In­vestors clear­ly did too, send­ing shares $SRPT up 12.60% to $84.60.

Louise Rodi­no-Kla­pac

Sarep­ta was sup­posed to go in­to Phase III ear­li­er. But in Sep­tem­ber, the FDA knocked back their plans, rais­ing con­cerns about the po­ten­cy as­says they were us­ing for the piv­otal study and com­mer­cial sup­ply. And then the last tri­al, 102, failed the func­tion­al end­point.

The com­pa­ny quick­ly re­solved the as­say is­sue as well as one of the things that In­gram said con­found­ed the 102 re­sults: an “im­prob­a­ble im­bal­ance” in the base­line char­ac­ter­is­tics of a cer­tain pa­tient co­hort. The oth­er? Ti­ter­ing vari­abil­i­ty with­in the dos­es — which is what 103 is de­signed to clean up.

More specif­i­cal­ly, Sarep­ta changed the way they mea­sured the how much AAV they were dos­ing, switch­ing from the tra­di­tion­al qPCR method to a lin­ear PCR method.

Look­ing at biop­sies at week 12, they found com­pa­ra­ble bio­mark­er re­sults — whether in terms of dy­s­trophin ex­pres­sion, dy­s­trophin pos­i­tive fibers or in­ten­si­ty — said CSO Louise Rodi­no-Kla­pac.

Count Baird an­a­lyst Bri­an Sko­r­ney in the “ex­treme­ly en­cour­aged” camp.

The con­tin­ued ab­sence of se­vere ad­verse events bodes well for Sarep­ta even as it falls be­hind Pfiz­er in ini­ti­at­ing a Phase III, he added:

By our count, this marks over 60 pa­tients who have been treat­ed with AAVrh74 to date (4 in Study 101, 41 in Study 102, 11 in Study 103, and 6 LGMD2E pa­tients), which we be­lieve makes it high­ly un­like­ly that the fact that AAVrh74-based gene ther­a­py has not re­sult­ed in com­ple­ment ac­ti­va­tion is due to ran­dom chance. While there were two SAEs in this study (1 in­creased liv­er en­zymes and 1 nau­sea/vom­it­ing) over­all we view these side ef­fects as eas­i­ly man­age­able and not life-threat­en­ing. All told, we view the ab­sence of com­ple­ment ac­ti­va­tion in Sarep­ta’s pro­gram as a key dif­fer­en­ti­at­ing fac­tor as com­pared to Pfiz­er’s and Sol­id’s AAV9-based as­sets which have been plagued with these ad­verse events.

Late Fri­day ap­proval; Trio of biotechs wind down; Stem cell pi­o­neer finds new fron­tier; Biotech icon to re­tire; 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.

I hope your weekend is off to a nice start, wherever you are reading this email. As for me, I’m trying to catch the tail of the Lunar New Year festivities.

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Pfiz­er lays off em­ploy­ees at Cal­i­for­nia and Con­necti­cut sites

Pfizer has laid off employees at its La Jolla, CA, and Groton, CT sites, according to multiple LinkedIn posts from former employees.

The Big Pharma confirmed to Endpoints News it has let go of some employees, but a spokesperson declined to specify how many workers were impacted and the exact locations affected. Earlier this month, the drug developer had confirmed to Endpoints it was sharpening its focus and doing away with some early research on areas such as rare disease, oncology and gene therapies.

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Jake Van Naarden, Loxo@Lilly CEO

Lil­ly en­ters ripe BTK field with quick FDA nod in man­tle cell lym­phoma

Eli Lilly has succeeded in its attempt to get the first non-covalent version of Bruton’s tyrosine kinase, or BTK, inhibitors to market, pushing it past rival Merck.

The FDA gave an accelerated nod to Lilly’s daily oral med, to be sold as Jaypirca, for patients with relapsed or refractory mantle cell lymphoma.

The agency’s green light, disclosed by the Indianapolis Big Pharma on Friday afternoon, catapults Lilly into a field dominated by covalent BTK inhibitors, which includes AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeiGene’s Brukinsa.

Ying Huang, Legend CEO

J&J, Leg­end say Carvyk­ti beat stan­dard ther­a­py in ear­li­er-line blood can­cer

J&J and Legend Biotech’s next step in turning their CAR-T therapy Carvykti into a potential megablockbuster has succeeded, the companies said Friday.

Carvykti achieved the primary endpoint — progression-free survival — in an open-label Phase III study testing the treatment in second- to fourth-line multiple myeloma patients. The CARTITUDE-4 trial, for which there aren’t any hard data yet, represents the biggest development for Carvykti’s ability to compete with Bristol Myers Squibb’s Abecma since its approval last February.

No­var­tis' ap­proved sick­le cell dis­ease drug fails to beat place­bo in PhI­II

Novartis’ sickle cell drug, approved in 2019 and branded as Adakveo, has failed an ongoing Phase III, according to preliminary results.

The Swiss pharma giant unveiled early data from the ongoing STAND Phase III study on Friday, saying that crizanlizumab showed no statistically significant difference between the drug at two different dose levels compared to placebo in annualized rates of vaso-occlusive crises that lead to a healthcare visit over the first year since being randomized into the trial.

Filip Dubovsky, Novavax CMO

No­vavax gets ready to take an­oth­er shot at Covid vac­cine mar­ket with next sea­son plans

While mRNA took center stage at yesterday’s FDA vaccine advisory committee meeting, Novavax announced its plans to deliver an updated protein-based vaccine based on new guidance.

Vaccines and Related Biological Products Advisory Committee (VRBPAC) members voted unanimously in favor of “harmonizing” Covid vaccine compositions, meaning all future vaccine recipients would receive a bivalent vaccine, regardless of whether they’ve gotten their primary series.

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FDA ap­proves an­oth­er in­di­ca­tion for Keytru­da, this time in the ad­ju­vant NSCLC set­ting

Merck’s blockbuster cancer treatment Keytruda has been handed another indication by the FDA.

The US regulator announced on Thursday that it has approved Keytruda to serve as an adjuvant treatment for non-small cell lung cancer (NSCLC), which is its fifth indication in NSCLC and 34th indication overall.

According to a Merck release, the approval is based on data from a Phase III trial, dubbed Keynote-091, which measured disease-free survival in patients who received chemotherapy following surgery. The data from Merck displayed that Keytruda cut down on the risk of disease recurrence or death by 27% versus placebo.

Steve Harr, Sana Biotechnology CEO

Four years in, Sana gets first FDA go-ahead to bring can­cer treat­ment in­to the clin­ic

Sana Biotechnology is finally headed to the clinic.

Thursday afternoon, the biotech announced the FDA had cleared its application to start a clinical trial for its allogeneic, or “off-the-shelf,” CAR-T cell therapy targeting the antigen CD19 for patients with B-cell lymphomas and leukemias. Sana said its therapy, dubbed SC291, was designed to evade the immune system, which could help cell therapy produce a more durable response in patients, a concern that has followed such off-the-shelf therapies that use donor cells as opposed to a patient’s own cells.

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Dutch biotech starts liq­ui­da­tion af­ter end­ing PhI­II in GVHD

A 13-year-old Dutch biotech is going through a liquidation process after an unexpected end to its Phase III trial testing whether its combination of two monoclonal antibodies was superior to Incyte’s Jakafi.

Xenikos had hoped to prove its investigational therapy, named T-Guard, was better than Jakafi at garnering a complete response in patients experiencing life-threatening complications in which new cells from a hematopoietic stem cell transplant begin to fight the body. Jakafi was approved for the indication, steroid-refractory acute graft-versus-host disease, in May 2019.

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