New Zol­gens­ma da­ta sug­gest com­pa­ra­ble ef­fi­ca­cy to Spin­raza — an­a­lysts

As No­var­tis awaits the FDA de­ci­sion on its spinal mus­cu­lar at­ro­phy (SMA) gene-ther­a­py, Zol­gens­ma, the com­pa­ny that de­vel­oped the treat­ment for the rare, dead­ly in­her­it­ed dis­or­der, AveX­is, pre­sent­ed da­ta snap­shots from on­go­ing tri­als on Sun­day, prompt­ing an­a­lysts to sug­gest that the one-shot ther­a­py was look­ing com­pa­ra­ble to Bio­gen’s ap­proved Spin­raza.

In the on­go­ing late-stage STR1VE study, de­signed to eval­u­ate the ef­fi­ca­cy and safe­ty of a one-time IV in­fu­sion of Zol­gens­ma in pa­tients with SMA Type 1 who are <6 months of age, da­ta showed pa­tients con­tin­ued to show event-free sur­vival well above nor­mal his­tor­i­cal con­trols, AveX­is sug­gest­ed at the Amer­i­can Acad­e­my of Neu­rol­o­gy an­nu­al meet­ing.

SMA caus­es mus­cle weak­ness and pro­gres­sive loss of move­ment, trig­gered by a ge­net­ic de­te­ri­o­ra­tion in the nerve cells con­nect­ing the brain and spinal cord to the body’s mus­cles. Ba­bies with type 1 rarely sur­vive be­yond the first few years of life, while most chil­dren with type 2 sur­vive in­to adult­hood. Types 3 and 4 don’t usu­al­ly af­fect life ex­pectan­cy. The Swiss drug­mak­er has sug­gest­ed a price of $4 -$5 mil­lion for Zol­gens­ma, which it ac­quired via its $8.7 bil­lion takeover of AveX­is.

An­oth­er sig­nif­i­cant up­date was the snap­shot from the STRONG study, which is eval­u­at­ing the in­trathe­cal de­liv­ery of Zol­gens­ma in pa­tients with SMA Type 2. Pa­tients were strat­i­fied in­to two groups based on age at time of dos­ing: pa­tients who are ≥6 months but <24 months, and pa­tients who are ≥24 months but <60 months. The pri­ma­ry ef­fi­ca­cy out­come for pa­tients in the first group is the abil­i­ty to stand with­out sup­port ≥3 sec­onds; the main goal for the sec­ond group is a change in Ham­mer­smith Func­tion­al Mo­tor Scale-Ex­pand­ed (HFMSE) score from base­line. Since dos­ing, 22 mo­tor mile­stones in 10 pa­tients have been achieved across Dose A and Dose B, in­clud­ing two pa­tients who gained the abil­i­ty to stand in­de­pen­dent­ly, one of whom went on to walk alone, and one pa­tient who gained the abil­i­ty to walk with as­sis­tance. The me­di­an du­ra­tion of fol­low-up was 6.5 months and all 30 pa­tients are alive.

“The av­er­age age at en­roll­ment in STRONG was 17 months…these re­sults are chal­leng­ing to in­ter­pret or com­pare with the Spin­raza da­ta since the Bio­gen/Io­n­is study en­rolled pa­tients who were slight­ly old­er (3 years at base­line). Thus, we be­lieve the most com­pa­ra­ble dat­a­point is ef­fi­ca­cy on the HFMSE, which was the pri­ma­ry end­point in Bio­gen/Io­n­is’ Spin­raza tri­al. On this mea­sure, AVXS-101 pro­duced a mean 4.2 point im­prove­ment at a me­di­an fol­low up time of 7.5 months; by com­par­i­son, Spin­raza gen­er­at­ed a ~3 point im­prove­ment at 9 months in the Phase III CHER­ISH study. The mag­ni­tude of these im­prove­ments are ob­vi­ous­ly very close to one an­oth­er, and when we think about STRONG/CHER­ISH de­signs and the re­cruit­ed tri­al pop­u­la­tions, the bal­ance of con­found­ing vari­ables prob­a­bly fa­vors the STRONG study a lit­tle, un­der­ly­ing our con­clu­sion that the ef­fi­ca­cy of gene ther­a­py and Spin­raza are prob­a­bly pret­ty sim­i­lar,” Stifel an­a­lysts wrote in a note.

Ever­core ISI’s Umer Raf­fat sug­gest­ed that in the sec­ond group, al­though Zol­gens­ma ap­pears to kick in faster, both the gene-ther­a­py and Bio­gen’s $BI­IB Spin­raza plateau at the same. But, there is one cru­cial caveat — the pa­tients in AveX­is tri­al seemed to have low­er HFMSE scores to be­gin with, he wrote.

Over­all, no treat­ment-emer­gent deaths have been pre­sent­ed in the new da­ta, he not­ed. Rough­ly two weeks ago, AveX­is dis­closed that one of the in­fants in the STR1VE-EU study died from an in­fec­tion, and au­thor­i­ties are in­ves­ti­gat­ing whether Zol­gens­ma played a role in the death. Al­though reg­u­la­to­ry bod­ies are ex­pect­ed to be ac­com­mo­dat­ing for safe­ty is­sues when it comes to a po­ten­tial once-and-done treat­ment for the lethal dis­ease, com­pe­ti­tion ab­sent these safe­ty con­cerns could cer­tain­ly tem­per adop­tion.

The AveX­is da­ta “looks com­pet­i­tive and like a vi­able op­tion for pa­tients, in­clud­ing new in­trathe­cal dos­ing for Type 2, etc, and be­yond just in­fants (where gene ther­a­py is most com­pet­i­tive to start). We think FDA ap­proval and a fair­ly ‘broad la­bel’ could be com­ing for No­var­tis as soon as this week. Our doc sur­vey sug­gests more than 1/3 of pa­tients could opt for this; hence, Bio­gen es­ti­mates may be too high for Spin­raza,” Jef­feries an­a­lysts wrote in a note.

PTC Ther­a­peu­tics $PTCT and Roche’s oral SMA ther­a­py, ris­diplam, will like­ly be tak­en to the FDA for re­view  lat­er this year for a broad pop­u­la­tion, and could be on the mar­ket by the end of 2020, they added.

“Bot­tom line — we could see a 1/3, 1/3, 1/3 split of mar­ket over time,” Jef­feries an­a­lysts said. Doc­tors sug­gest gene ther­a­pies “could be 30-33% share of new SMA Type I-III pa­tients over time. An es­ti­mat­ed 20-25% could look to switch from Spin­raza to gene ther­a­py (de­pends on weight of pa­tient). 2) Sim­i­lar­ly, docs sug­gest 1/3 share for oral ris­diplam, too, af­ter 3-5 years; 3) Com­men­tary by docs sug­gests an even split of opin­ions on the mar­ket as well — from oral pills ‘very ap­peal­ing’ and ‘game chang­er’ and ‘es­pe­cial­ly at­trac­tive for teens/adults’ to oth­er ther­a­pies need more da­ta and like­ly com­bo,” cit­ing their sur­vey.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Jim Scholefield via PR Newswire

Mer­ck los­es its chief dig­i­tal of­fi­cer, spot­light­ing tal­ent hunt for the hottest ti­tle in Big Phar­ma

Over the last few years we’ve seen the chief digital officer title become one of the hottest commodities in Big Pharma as global organizations hunt the best talent to sharpen the cutting edge of their tech platforms.

But Merck just discovered how hard it may be to keep them focused on pharma.

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Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

Kathy High dedicated the past seven years of her life shepherding experimental gene therapies she’s developed at Children’s Hospital of Philadelphia toward the market as president and head of R&D at Spark Therapeutics. Now that the biotech startup is fully absorbed into Roche — with an FDA approval, a $4.3 billion buyout and a promising hemophilia program to boast — she’s ready to move on.

Roche confirmed her departure with Endpoints News and noted “she will take some well-deserved time off and then will begin a new chapter in a sabbatical at a university.”

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

“[We were] trying to find a test case for how to demonstrate if our technology could rapidly prepare,” Zaks told Endpoints News.

Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

“I was immediately thinking like, ‘Hey, this is something that if needed, we can play a role,'” Oostvogels told Endpoints.

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Say good­bye to Toca­gen, strug­gling brain can­cer biotech to re­verse merge with Forte Bio­sciences

Five months after a huge Phase III failure triggered mass layoffs at the company, Tocagen will sign itself out of existence.

The biotech, once focused on brain cancer, announced it has signed a reverse merger agreement with Forte Biosciences, a biotech tackling atopic dermatitis and other inflammatory skin diseases. Tocagen’s stock shot up 85% on the news, although that only translated to a 41-cent bump for a company that saw the last of its value go poof in September. The new company will trade under the ticker $FBRX.

JJ Bienaimé (BioMarin via YouTube)

Speedy re­view and no ad­comm for Bio­Mar­in's pi­o­neer­ing he­mo­phil­ia gene ther­a­py

BioMarin’s keenly anticipated hemophilia A gene therapy — which CEO JJ Bienaimé envisions pricing at an eye-watering $2 million to $3 million a shot — has secured red carpet treatment at the FDA.

The therapy, fondly called valrox, has won priority review — and there the agency has indicated there are no plans for an advisory committee meeting. The US regulator’s final decision is expected by August 21. If approved, it will be the pioneering gene therapy for hemophilia.

“While the company…indicated that FDA does not currently plan on convening an advisory committee meeting to discuss the merits of the application, we caution that the possibility of such still remains as the agency digs into its review, which could be interpreted negatively by the Street,” BMO Capital Market’s George Farmer wrote.

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

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Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

“I’m ok, I don’t have Ebola,” Pascal told them. “I see that death toll rising and I can’t not do something about it.”

Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Phar­ma­co­ge­net­ics: FDA re­leas­es ta­ble of gene-drug in­ter­ac­tions

The FDA on Thursday published a table identifying more than 50 gene-drug interactions that the agency says are supported by scientific evidence and announced it is considering new approaches to evaluating pharmacogenetic associations.

“Consistent with our mission to protect and promote public health, we believe it is important to take steps now to help ensure that claims being made for pharmacogenetic tests offered today are grounded in sound science to avoid inappropriate management of patients’ medications,” said Center for Devices and Radiological Health Director Jeff Shuren and Center for Drug Evaluation and Research Director Janet Woodcock.

Don't let Ab­b­Vie fool FTC with an easy di­vesti­ture, plead crit­ics in lat­est at­tack on $63B Al­ler­gan buy­out

If the FTC must let AbbVie and Allergan go ahead with their merger, at least make them divest their latest blockbuster on the market, a chorus of unions, consumer groups and public interest organizations plead in a new attempt to rein in the megamerger.

There’s a second part to their argument: If the antitrust watchdog does greenlight the divestiture AbbVie wants, then at least ensure the pharma giant cannot corner its future rivals with its exclusionary tactics.

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