While No­var­tis ban­ish­es Zol­gens­ma scan­dal scars — Bio­gen goes on a Spin­raza 'of­fen­sive'

While No­var­tis painstak­ing­ly works to mop up the stench of the da­ta ma­nip­u­la­tion scan­dal as­so­ci­at­ed with its ex­pen­sive gene ther­a­py for spinal mus­cu­lar at­ro­phy (SMA) Zol­gens­ma— ri­val Bio­gen is at­tempt­ing to ex­pand the use of its SMA ther­a­py, Spin­raza. 

The US drug­mak­er $BI­IB se­cured US ap­proval for Spin­raza for use in the of­ten fa­tal ge­net­ic dis­ease in 2016. The ap­proval cov­ered a broad range of pa­tients with in­fan­tile-on­set (most like­ly to de­vel­op Type 1) SMA. 

Spin­raza’s mar­ket­ing ap­pli­ca­tion was giv­en the nod large­ly on the ba­sis of the piv­otal 121-pa­tient EN­DEAR study, which showed 40% of pa­tients treat­ed with Spin­raza saw an im­prove­ment in mo­tor mile­stones, com­pared to none in the con­trol arm. Long term da­ta from 24 pa­tients across dif­fer­ent Spin­raza tri­als found that chil­dren with lat­er-on­set SMA (Type 2 or Type 3) saw mo­tor func­tion sta­bi­lize or im­prove for up to near­ly six years, in con­trast to the ex­pect­ed de­cline if they did not re­ceive treat­ment. 

On Wednes­day, Bio­gen said it was go­ing to test a high­er dose of Spin­raza in a 126-pa­tient tri­al to eval­u­ate whether it was more po­tent (and safe) in SMA pa­tients. The three-part tri­al in­cludes an open-la­bel safe­ty eval­u­a­tion, fol­lowed by a dou­ble-blind, ran­dom­ized treat­ment pe­ri­od, which will lead to an open-la­bel treat­ment pe­ri­od. 

Af­ter the safe­ty eval­u­a­tion, the tri­al will com­pare two load­ing dos­es of 50 mil­ligrams (mg), 15 days apart, fol­lowed by a main­te­nance dose of 28 mg every four months with the cur­rent FDA-ap­proved ad­min­is­tra­tion of Spin­raza, which is four load­ing dos­es with 12 mg main­te­nance dos­es every four months. 

Bio­gen’s orig­i­nal dose 12 mg se­lec­tion was based on pre­clin­i­cal da­ta, Ever­core ISI an­a­lyst Umer Raf­fat wrote in a note en­ti­tled “Spin­raza on the of­fen­sive” last week.

The rea­son Bio­gen did not test a high­er than 12 mg dose is due to pre­clin­i­cal tox­i­c­i­ty con­cerns seen in mon­keys, he added. “These mon­key tox find­ings hap­pened at 3 mg and 4 mg dos­es … hu­man equiv­a­lent of this is 450-520 mg. For ref­er­ence, the high­er dos­es in new tri­al have an­nu­al Spin­raza of 140-156 mg (i.e., well be­low).”

In terms of ef­fi­ca­cy, a high­er dose could po­ten­tial­ly be ben­e­fi­cial, Raf­fat ar­gued. “High­er dose could be bet­ter in in­fants … Ph 2 in­fan­tile on­set shows much bet­ter mo­tor mile­stones at 12 mg vs 6 mg. Even if 12 mg is op­ti­mal in in­fants, there’s still a pos­si­bil­i­ty that the dose in teenagers/adults should be high­er (was nev­er test­ed).” 

Mean­while, No­var­tis $NVS and its AveX­is unit are putting out fires sur­round­ing Zol­gens­ma, which was ap­proved ear­li­er this year. Priced at $2.1 mil­lion — it is the world’s most ex­pen­sive ther­a­py. Last month, it emerged AveX­is had in­formed the FDA in late June about the ma­nip­u­la­tion of da­ta used in its quest to pro­cure FDA ap­proval for Zol­gens­ma. 

Be­fore that, safe­ty was a po­ten­tial con­cern, af­ter a British in­fant suc­cumbed to a se­vere res­pi­ra­to­ry in­fec­tion fol­lowed by neu­ro­log­i­cal com­pli­ca­tions in a Eu­ro­pean Zol­gens­ma study. How­ev­er, com­pa­ny ex­ec­u­tives on Thurs­day clar­i­fied that an in­ves­ti­ga­tion had con­clud­ed that the death was un­re­lat­ed to the drug

Ex­ec­u­tives rep­re­sent­ing the Swiss drug­mak­er al­so un­der­scored pos­i­tive long-term safe­ty and ef­fi­ca­cy da­ta on the ther­a­py. 

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

CDC’s Robert Redford, NIAID’s Anthony Fauci, Admiral Brett Giroir at HHS, and FDA’s Stephen Hahn prepare to testify at a House hearing on June 23 (Getty)

'Ex­treme­ly po­lit­i­cal' — Trump neuters FDA's at­tempt to strength­en vac­cine EUA, ques­tions need to length­en process

Stephen Hahn went before a Senate committee Wednesday and declared he’s fighting. “Every one of the decisions we have reached has been made by career FDA scientists based on science and data, not politics,” he exclaimed, adding that “FDA will not permit any pressure from anyone to change that. I will fight for science.”

A few hours later, he was undermined by President Donald Trump when a reporter asked if he was okay with stricter vaccine guidelines that the FDA was said to be cooking up. “That has to be approved by the White House. We may or may not approve it. That sounds like a political move,” he decided.

CEO Markus Warmuth (Monte Rosa)

Monte Rosa rakes in $96M Se­ries B as it pre­pares 'mol­e­c­u­lar glue' plat­form for IND-en­abling stud­ies

About four months after completing an extension to its Series A, Monte Rosa Therapeutics is putting its next foot forward with another heap of cash.

The Boston-based biotech is back with $96 million in Series B financing with a goal to get its lead program ready for IND-enabling studies by the end of the year. Though Monte Rosa is keeping its specific target a secret for now, the company has been researching how to utilize its protein degradation technology in breast cancer and non-small cell lung cancer, among other areas.

Chair of FDA's vac­cine ad­comm — who's al­so a lead in­ves­ti­ga­tor of Mod­er­na's vac­cine — re­cus­es her­self from Covid-19 talks

When the FDA’s Vaccines and Related Biological Products Advisory Committee meets next month to discuss the development and authorization of Covid-19 vaccines, the chairwoman won’t be there.

Hana El Sahly has recused herself from the expert panel’s review of the topic, citing her role as a lead investigator in Moderna’s Phase III trial, Reuters reported. An associate professor of virology and microbiology at Baylor College of Medicine in Houston, El Sahly was appointed the chairwoman last year.

David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

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Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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Jim Roberts and Brian Finrow (Lumen Bioscience)

With a $4M fed­er­al grant, Lu­men jumps in­to the Covid-19 treat­ment race

It’s been less than a month since Lumen Bioscience announced a $16 million Series B to engineer spirulina — a nutrient-packed super food — for diseases like traveler’s diarrhea, norovirus and C. difficile colitis. And now, the biotech has pulled in another $4 million to do the same for Covid-19.

The approach is quite similar to other gastrointestinal targets the company is pursuing, co-founders and Brian Finrow and Jim Roberts said. The Seattle-based company is working on a camelid antibody cocktail to combat GI infection common among Covid-19 patients. In a study published in the American Journal of Gastroenterology, a majority of Covid-19 patients showed GI and respiratory symptoms, and 25% had only GI symptoms.

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.