San­ther­a's Duchenne ef­fort gets a boost on pos­i­tive PhI­Ia for al­ter­na­tive steroid va­morolone — though there's a lot left to prove

Months af­ter San­thera got its hands on a sec­ond Duchenne mus­cu­lar dy­s­tro­phy drug, the Swiss com­pa­ny is get­ting an ear­ly look at how it im­proves mus­cle func­tion. But se­ri­ous ques­tions re­main as it takes on a field stuffed with en­trenched ri­vals and con­tro­ver­sy.

Er­ic Hoff­man

Rever­a­Gen was in charge of the Phase IIa ex­ten­sion, which com­pared dif­fer­ent dos­es of va­morolone with nat­ur­al his­to­ry con­trols. With 12 boys (aged 4 to 7) in each of four treat­ment groups, in­ves­ti­ga­tors test­ed 0.25, 0.75, 2.0 and 6.0 mg/kg/day in the study and pub­lished the re­sults in Neu­rol­o­gy.

With­out spelling out num­bers, the com­pa­ny not­ed that pa­tients reg­is­tered sta­tis­ti­cal­ly sig­nif­i­cant and pro­por­tion­al im­prove­ments from base­line on mul­ti­ple fronts, in­clud­ing the pri­ma­ry end­point of time to stand from supine. Sec­ondary end­points re­gard­ing mo­tor func­tion out­comes span time to run/walk 10 me­ters, time to climb stairs, 6-minute walk test and North Star Am­bu­la­to­ry Test — with the high­est dose out­per­form­ing the low­est in a no­table man­ner.

Per­haps more im­por­tant­ly to their point, Rever­a­Gen re­port­ed that va­morolone ap­pears to trig­ger less adren­al sup­pres­sion, in­sulin re­sis­tance and bone mor­bidi­ties nor­mal­ly ob­served with oth­er cor­ti­cos­teroids.

“Based on these da­ta, va­morolone has po­ten­tial to re­place stan­dard cor­ti­cos­teroids cur­rent­ly used in pa­tients with DMD,” Rever­a­Gen CEO said in a state­ment.

Thomas Meier

Cor­ti­cos­teroids such as pred­nisone and de­flaza­cort rep­re­sent the fun­da­men­tal DMD treat­ments, pro­vid­ing a point of ref­er­ence for new and ex­per­i­men­tal ther­a­pies. They are al­so dirt cheap, un­til Marathon ac­quired rights to de­flaza­cort, rushed it through an FDA ap­proval as Em­flaza and jacked up the price from rouhg­ly $1,000 to $89,000 in a no­to­ri­ous case of price goug­ing. The avail­abil­i­ty of pred­nisone at pen­nies per pill, though, keeps the bar high on any re­place­ment.

When San­thera ac­quired Idor­sia’s op­tion for va­morolone late last year (in ex­change for $20 mil­lion up­front and 1 mil­lion shares), CEO Thomas Meier high­light­ed how it fits in­to their port­fo­lio strat­e­gy to cov­er a broad Duchenne pa­tient spec­trum, “ir­re­spec­tive of ge­net­ic back­ground, dis­ease stage or age.” That’s in con­trast with the tar­get­ed ap­proach­es oth­ers such as Sarep­ta and start­up Ex­on­ics have tak­en, with their re­spec­tive ex­on-skip­ping and gene edit­ing ef­forts.

It has not worked out smooth­ly, though. San­thera’s oth­er Duchenne can­di­date, idebenone, has pre­vi­ous­ly been de­nied ac­cel­er­at­ed ap­proval by the FDA and slapped down by the EMA. (The drug is mar­ket­ed as Rax­one in Eu­rope to treat Leber’s hered­i­tary op­tic neu­ropa­thy.)

But San­thera has since man­aged to notch or­phan drug des­ig­na­tions on both sides of the At­lantic and kick­start­ed a Phase III tri­al eval­u­at­ing the ef­fi­ca­cy of idebenone in de­lay­ing the loss of res­pi­ra­to­ry func­tion in Duchenne pa­tients al­ready re­ceiv­ing cor­ti­cos­teroids.

Mean­while, Rever­a­Gen is in the midst of a Phase IIb study with 120 cor­ti­cos­teroid-naive boys, com­par­ing the two high­est dos­es of va­morolone (2.0 and 6.0 mg/kg/day) with pred­nisone and place­bo. It’s slat­ed to con­clude next year.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Israel Lowy (Regeneron)

#ES­MO20: 'As good as any PD-1 out there': Re­gen­eron flash­es PD-(L)1 lung can­cer da­ta to ri­val Mer­ck

Regeneron entered the PD-(L)1 game late, so they devised a two-pronged strategy to catch up with Big Pharma rivals: They would push it into cancers where PD-1s had yet been tested, and they would prove that it’s as powerful in the big indications as any other on the market.

They cleared a hurdle on the first goal Friday, showing a 31% response in patients with the rare skin cancer basal cell carcinoma. And with the data they’re rolling out Monday, Regeneron cancer chief Israel Lowy is ready to declare success on the second.

Frank Zhang (AP Images)

Rocked by cus­toms in­ves­ti­ga­tion, Leg­end's CFO takes over as CEO Frank Zhang placed un­der house ar­rest

When Frank Zhang stepped down from GenScript — the contract research group he’s run for 18 years — to take up the CEO post at its CAR-T focused spinout Legend Biotech, he assured analysts that he was in for the long haul.

Just 49 days later, though, he’s been forced to hand back the title.

In a dramatic turn of events, Legend disclosed that Zhang is under house arrest in China as part of a customs investigation involving GenScript. While he remains the chairman, CFO Ying Huang has been tapped to double as interim CEO.

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Two wild weeks for Grail end in $8B Il­lu­mi­na buy­out

Grail’s whirlwind two weeks have ended in the wealthy arms of its former founder and benefactors.

Illumina has shelled out $8 billion to reacquire the closely-watched liquid biopsy startup they spun out just 5 years ago and sold off much of its shares just 3 years ago. The deal comes nearly two weeks after the well-heeled startup filed for a potentially massive IPO — one that was disrupted just a week later when Bloomberg reported that Illumina was in talks to buy their former spinout for up to $8 billion.

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Eli Lilly CSO Dan Skovronsky (file photo)

UP­DAT­ED: #ES­MO20: Eli Lil­ly shows off the da­ta for its Verzenio suc­cess. Was it worth $18 bil­lion?

The press release alone, devoid of any number except for the size of the trial, added nearly $20 billion to Eli Lilly’s market cap back in June. Now investors and oncologists will get to see if the data live up to the hype.

On Sunday at ESMO, Eli Lilly announced the full results for its Phase III MonarchE trial of Verzenio, showing that across over 5,000 women who had had HR+, HER2- breast cancer, the drug reduced the odds of recurrence by 25%. That meant 7.8% of the patients on the drug arm saw their cancers return within 2 years, compared with 11.3% on the placebo arm.

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Roche vaults to the front of the NL­RP3 clin­i­cal race, pay­ing $448M up­front to bag In­fla­zome

Roche is going all in on NLRP3.

The pharma giant is putting down $448 million (€380 million) upfront to snatch Novartis-backed Inflazome, which makes it a clinical player in the space overnight.

Dublin and Cambridge, UK-based Inflazome is the second NLRP3-focused biotech Roche has acquired in less than two years, and although no numbers were disclosed in the Jecure buyout, this is almost certainly a much larger deal.

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As­traZeneca pub­lish­es Covid-19 vac­cine PhI­II pro­to­cols in lock­step with Mod­er­na and Pfiz­er. How are they dif­fer­ent?

Following in the steps of Moderna and Pfizer, the other two American drugmakers currently in Phase III trials for their Covid-19 vaccines, AstraZeneca posted its own study protocols over the weekend. The move is the latest in a series of rare peeks behind the curtain, as such blueprints are typically shared once such trials are completed.

“Given the unprecedented global impact of the Coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial. As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials. AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company said in a statement.

Greg Friberg (File photo)

#ES­MO20: Am­gen team nails down sol­id ear­ly ev­i­dence of AMG 510’s po­ten­tial for NSCLC, un­lock­ing the door to a wave of KRAS pro­grams

The first time I sat down with Amgen’s Greg Friberg to talk about the pharma giant’s KRAS G12C program for sotorasib (AMG 510) at ASCO a little more than a year ago, there was high excitement about the first glimpse of efficacy from their Phase I study, with 5 of 10 evaluable non-small cell lung cancer patients demonstrating a response to the drug.

After decades of failure targeting KRAS, sotorasib offered the first positive look at a new approach that promised to open a door to a whole new approach by targeting a particular mutation to a big target that had remained “undruggable” for decades.

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#ES­MO20: Out to beat Tagris­so, J&J touts 100% ORR for EGFR bis­pe­cif­ic/TKI com­bo — fu­el­ing a quick leap to PhI­II

J&J’s one-two punch on EGFR-mutant non-small cell lung cancer has turned up some promising — although decidedly early — results, fueling the idea that there’s yet room to one up on third-generation tyrosine kinase inhibitors.

Twenty out of 20 advanced NSCLC patients had a response after taking a combination of an in-house TKI dubbed lazertinib and amivantamab, a bispecific antibody targeting both EGFR and cMET engineered on partner Genmab’s platform, J&J reported at ESMO. All were treatment-naïve, and none has seen their cancer progress at a median follow-up of seven months.