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.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Tony Coles, Cerevel CEO

Cerev­el takes the pub­lic of­fer­ing route, with a twist — rais­ing big mon­ey thanks to ri­val da­ta

As public biotechs seek to climb out of the bear market, a popular strategy to raise cash has been through public offerings on the heels of positive data. But one proposed raise Wednesday appeared to take advantage not of a company’s own data, but those from a competitor.

Cerevel Therapeutics plans to raise $250 million in a public offering and another $250 million in debt, the biotech announced Wednesday afternoon, even though it did not report any news on its pipeline. However, the move comes days after rival Karuna Therapeutics touted positive Phase III data in schizophrenia, a field where Cerevel is pursuing a similar program.

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Who are the women blaz­ing trails in bio­phar­ma R&D? Nom­i­nate them for End­points' 2022 spe­cial re­port

Over the past three years, Endpoints News has spotlighted 60 women who have blazed trails and supercharged R&D across the biopharma world. And judging from the response we’ve received, to both our special reports and live events, telling their stories — including any obstacles they may have had to overcome — has inspired our readers in many different ways.

But change takes time, and the fact remains that women are still underrepresented at the upper ranks of the drug-making world.

Bernat Olle, Vedanta Biosciences CEO

Cit­ing 'chal­leng­ing eco­nom­ic en­vi­ron­ment,' PhI­II-ready mi­cro­bio­me biotech lays off 20% of staffers

The market downturn isn’t just sweeping up public biotechs.

Vedanta Biosciences, a developer of oral drugs derived from the human microbiome, is laying off about 20% of its staff — an unfortunately common occurrence these days. But CEO Bernat Olle took the unusual step of sharing the decision on LinkedIn and offering to connect the employees being let go with any company that’s hiring in their areas.

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Hervé Affagard, MaaT Pharma CEO

One year in­to clin­i­cal hold, FDA has more ques­tions about 'pooled' mi­cro­bio­me ther­a­py

The FDA is still wary about a trial testing a microbiome therapy in patients with steroid-resistant acute graft-versus-host disease (aGVHD).

A year after MaaT Pharma’s IND application in the US was first met with a clinical hold, the French biotech said the agency is maintaining the hold. The crux of the matter, MaaT suggested, has to do with the way it puts together its drug candidate, which is administered as an enema (i.e. an injection of fluid into the bowel).

Up­dat­ed: Amid mas­sive re­struc­tur­ing, Bio­gen looks to re­duce phys­i­cal pres­ence in Boston

Biogen is putting a sizable chunk of office and research space in Kendall Square and Weston, MA up for sublease, marking another big change as the biotech grapples with the aftershock of a disastrous and controversial rollout for its Alzheimer’s drug.

The subbleases are “part of Biogen’s overall implementation of the ‘Future of Work,’ which is allowing us to optimize our footprint and reduce the amount of space we occupy, taking into consideration new elements such as the hybrid work model,” Biogen spokesperson Ashleigh Koss wrote in a statement to Endpoints News, adding that the company has had subleases across several buildings for years.

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Saurabh Saha, Centessa CEO (BIO19)

One of 2021's star biotech play­ers flags an­oth­er big set­back for the pipeline

Two months after scuttling their lead drug, Centessa’s executive team is back with the latest in a series of setbacks that have tanked its stock and blown holes in its strategic lineup of biotech subs.

The company reported in its Q2 post today that it has decided to scrap ZF874 after a patient demonstrated elevated liver enzymes — a classic red safety flag — in a Phase I study for alpha-1-antitrypsin (A1AT).

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Illustration: Kim Ryu for Endpoints News

Why non-opi­oid pain drugs keep fail­ing — and what's next for the field

In 1938, Rita Levi-Montalcini was forced to move her lab into her bedroom in Turin, as Mussolini’s facist government expelled Jewish people from studying or working in schools in Italy. Levi-Montalcini, then just a few years out of medical school and using sewing needles as scalpels in her makeshift lab, would soon discover nerve growth factor, or NGF, in chicken embryos.

Her discoveries formed the basis of our understanding of the peripheral nervous system and how cells talk to each other, and Levi-Montalcini went on to win the Nobel Prize in 1986. Much later, NGF was hailed as a promising target for new pain therapies, with some analysts quoting an $11 billion market. However, the latest anti-NGF candidate, Pfizer and Eli Lilly’s tanezumab, was rejected by the FDA last year because of a side effect that dissolved bone in some of its patients.

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Pfiz­er launch­es re­bate pro­gram for rare dis­ease pa­tients who have to stop tak­ing Panzy­ga

Pfizer is launching its second-ever rebate program, this time for Panzyga, its treatment for a rare neurological disease of the peripheral nerves.

The program began last month, according to STAT which first reported the news, and offers a refund of out-of-pocket costs for patients who must discontinue their course before the fifth treatment for “clinical reasons.”

Panzyga was approved back in 2018 to treat primary immunodeficiency (PI) in patients two years and older and chronic immune thrombocytopenia (cITP) in adults. It has since picked up an indication in chronic inflammatory demyelinating polyneuropathy (CIDP), a condition that’s characterized by weakness of the arms or legs, tingling or numbness, and a loss of deep tendon reflexes, according to the NIH.