John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

With lumasir­an on the FDA's doorstep, Al­ny­lam reads out new PhI­II da­ta in PH1

Just over a month away from its De­cem­ber PDU­FA date, Al­ny­lam flaunt­ed new da­ta from two Phase III stud­ies to back lumasir­an in pri­ma­ry hy­per­ox­aluria type 1 (PH1), a rare liv­er con­di­tion.

The Cam­bridge, MA-based biotech snagged a pri­or­i­ty re­view for the can­di­date back in June, and got pos­i­tive feed­back from the EMA’s Com­mit­tee for Med­i­c­i­nal Prod­ucts for Hu­man Use just last week. Lumasir­an us­es RNA in­ter­fer­ence (RNAi) to si­lence the gene for gly­co­late ox­i­dase, an en­zyme used in the pro­duc­tion of ox­alate.

On Thurs­day at this year’s ASN Kid­ney Week, Al­ny­lam read out 6-month re­sults from a study in chil­dren be­tween 3 months and 6 years old, and 12-month re­sults from a tri­al in pa­tients old­er than 6 years.

In the lat­ter study, dubbed IL­LU­MI­NATE-A, pa­tients ini­tial­ly placed in the treat­ment arm were shown to main­tain a re­duc­tion in 24-hour ox­alate ex­cre­tion, with a 64% mean re­duc­tion rel­a­tive to base­line. Of this group, 88% achieved nor­mal or near-nor­mal uri­nary ox­alate lev­els, ac­cord­ing to Al­ny­lam. Pa­tients with PH1 tend to over­pro­duce uri­nary ox­alate, which po­ten­tial­ly leads to kid­ney stones, or in some cas­es kid­ney fail­ure at a young age.

Those who were ini­tial­ly in the place­bo arm but crossed over to lumasir­an showed a 57% mean re­duc­tion in 24-hour uri­nary ox­alate ex­cre­tion af­ter 6 months of treat­ment, the com­pa­ny an­nounced. About 77% of these pa­tients reached nor­mal or near-nor­mal uri­nary oxy­late lev­els.

Al­ny­lam says there were no deaths, se­ri­ous ad­verse events (SAEs), treat­ment in­ter­rup­tions or dis­con­tin­u­a­tions linked to the drug. One pa­tient ex­pe­ri­enced urosep­sis, but the biotech said it was un­re­lat­ed to the ex­per­i­men­tal can­di­date. Some pa­tients ex­pe­ri­enced mild in­jec­tion site re­ac­tions, in­clud­ing ery­the­ma, pain, pru­ri­tus, or swelling.

As for the pe­di­atric study, IL­LU­MI­NATE-B, those in the treat­ment arm showed a 72% mean re­duc­tion in spot uri­nary ox­alate to cre­a­ti­nine ra­tio from base­line, av­er­aged across months 3 to 6, ac­cord­ing to the biotech. Half of pa­tients ex­pe­ri­enced nor­mal or near-nor­mal uri­nary ox­alate lev­els.

A pre­lim­i­nary analy­sis al­so showed that 8 of 18 pa­tients — about 44% — had im­prove­ments in nephro­cal­ci­nosis. At base­line, 14 pa­tients ex­pe­ri­enced the dis­or­der, char­ac­ter­ized by too much cal­ci­um de­po­si­tion in the kid­neys. At the 6-month mark, no pa­tients wors­ened, 10 re­mained sta­ble, and 8 showed bi­lat­er­al or uni­lat­er­al im­prove­ments, Al­ny­lam said.

The biotech re­port­ed no deaths, SAEs, dis­con­tin­u­a­tions of treat­ment or with­drawals from the study. The ef­fi­ca­cy and safe­ty re­sults, it said, were sim­i­lar to those ob­served in IL­LU­MI­NATE-A. Like that study, one pa­tient ex­pe­ri­enced an SAE that the biotech said wasn’t linked to the drug (in this case, a vi­ral in­fec­tion).

In an on­go­ing Phase II open-la­bel ex­ten­sion study, re­searchers ob­served sus­tained re­duc­tions in uri­nary ox­alate ex­cre­tion and an “ac­cept­able safe­ty pro­file,” ac­cord­ing to Al­ny­lam. They al­so found that af­ter long-term treat­ment, few­er pa­tients had re­nal stones. Pri­or to the study, 6 of 20 pa­tients re­port­ed re­nal stones. In the Phase I/II Part B study, 4 of 20 pa­tients re­port­ed them. And dur­ing Phase II (with up to 22 months of treat­ment), no pa­tients re­port­ed them, Al­ny­lam said.

“Based on longer term fol­low-up from the IL­LU­MI­NATE-A and Phase 2 open-la­bel ex­ten­sion stud­ies, in­ves­ti­ga­tors pre­sent­ed da­ta show­ing en­dur­ing re­duc­tions of uri­nary ox­alate – the dis­ease-caus­ing metabo­lite in PH1. More­over, we be­lieve that new­ly pre­sent­ed re­sults of ex­plorato­ry end­points pro­vide pre­lim­i­nary ev­i­dence that re­duc­tions in uri­nary ox­alate may lead to re­duced rates of re­nal stone events and im­prove nephro­cal­ci­nosis in some pa­tients,” Pritesh Gand­hi, VP and gen­er­al man­ag­er of the lumasir­an pro­gram, sum­ma­rized in a state­ment.

Around 2011, ma­jor com­pa­nies like Pfiz­er and Ab­bott bailed from the RNAi field, eat­ing heavy loss­es. But Al­ny­lam CEO John Maraganore re­mained stead­fast, pledg­ing to bring 5 RNAi drugs in­to late-stage de­vel­op­ment by 2015.

If ap­proved, lumasir­an would be Al­ny­lam’s third ap­proved drug in the last three years. The biotech has two oth­er RNAi drugs in late-stage de­vel­op­ment, in­clud­ing in­clisir­an (now part­nered with No­var­tis), plus a la­bel ex­pan­sion for patisir­an in the works. Sev­en oth­er can­di­dates are in ear­ly-stage de­vel­op­ment, in­clud­ing one for Covid-19.

Forge Bi­o­log­ics’ cGMP Com­pli­ant and Com­mer­cial­ly Vi­able Be­spoke Affin­i­ty Chro­matog­ra­phy Plat­form

Forge Biologics has developed a bespoke affinity chromatography platform approach that factors in unique vector combinations to streamline development timelines and assist our clients in efficiently entering the clinic. By leveraging our experience with natural and novel serotypes and transgene conformations, we are able to accelerate affinity chromatography development by nearly 3-fold. Many downstream purification models are serotype-dependent, demanding unique and time-consuming development strategies for each AAV gene therapy product1. With the increasing demand to propel AAV gene therapies to market, platform purification methods that support commercial-scale manufacturing of high-quality vectors with excellent safety and efficacy profiles are essential.

Who’s spend­ing and who’s cut­ting from Big Phar­ma’s $127B R&D bud­get? Here are the top 15 play­ers

A couple of the Big 15 biopharma companies in R&D hit the gas on research spending last year. Merck and Sanofi still have lots to prove in the pipeline, and they’re willing to gamble large sums to make a better future for themselves.

Doing nothing would be infinitely worse.

But collectively, the top players rang up a modest 2.4% increase in spending in 2022, which didn’t cover inflationary pressures. And that set the tone for an extraordinarily cautious year for the industry — even as it laid out about $127 billion to advance new drugs or up the ante on approved therapies.

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Jeff Bluestone (R), Sonoma Biotherapeutics CEO

Jef­frey Blue­stone brings his start­up haul to $400M+, join­ing forces with Re­gen­eron on cell ther­a­pies

These days, when Jeffrey Bluestone gets together with his contemporaries in science, the conversation often turns to retirement plans.

But a little more than three years ago, Bluestone reached a momentous turning point in his career, exiting a prestigious post at UCSF, where he had spent decades in the scientific pursuit of new therapies. And it had nothing to do with retirement anytime in the near future.

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Mihael Polymeropoulos, Vanda Pharmaceuticals CEO

Van­da wins court case against FDA over dis­clo­sure of CRL de­tails for sleep drug

DC District Court Judge Christopher Cooper today granted Vanda Pharma’s request to require the FDA to disclose more info on the complete response letter for its sleep disorder drug Hetlioz.

The melatonin receptor agonist is approved by the FDA to treat non-24-hour sleep-wake disorder, a circadian rhythm disorder. But in 2018 Vanda filed a supplemental application to market Hetlioz as a treatment for jet lag, which the FDA rejected in August 2019, with few details on what Vanda needed to correct course, according to the company.

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While Jemperli (dostarlimab) is already approved for a subset of patients with second-line endometrial cancer, GSK set out in the Phase III RUBY trial to test it as an earlier line of treatment while also enrolling a broader group of patients. In an interim analysis, Jemperli was shown to extend progression-free survival for both the subset and the overall trial population when added to chemotherapy.

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Doug Williams, departing Codiak BioSciences CEO

Co­di­ak files for Chap­ter 11 bank­rupt­cy as most ex­ec­u­tives head for the ex­it

Codiak BioSciences has filed for Chapter 11 bankruptcy, spelling an end to the employment of most executives, including founder Doug Williams, as the biotech says it “expects to consummate a sale.”

The eight-year journey at Codiak is nearing an end with Williams; CFO Linda Bain; medical chief David Mauro; scientific head Sriram Sathyanarayanan; legal and compliance chief Yalonda Howze; and SVP of HR Nicole Barna all packing up their bags in the first few days of April. Chief technology officer Konstantin Konstantinov will stay.

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Brain­Storm gets FDA ad­comm for ALS drug af­ter failed tri­al and RTF

BrainStorm Cell Therapeutics has had a rocky road trying to get its ALS treatment through to the FDA, including a particularly difficult setback after the FDA slapped the company with a refusal to file (RTF) letter in November after it submitted its original BLA in September last year.

But there’s a glimmer of hope for BrainStorm’s ALS treatment, NurOwn – the FDA will hold an advisory committee meeting to discuss the company’s BLA for the treatment, the company announced today.

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Sally Susman, Pfizer EVP and chief corporate affairs officer

Q&A: Pfiz­er cor­po­rate com­mu­ni­ca­tions chief Sal­ly Sus­man dis­cuss­es book craft­ed in pan­dem­ic and per­son­al lessons

From the political arena to the finance and beauty industries to pharmaceuticals, Pfizer’s Sally Susman has broken barriers, stereotypes and conventions. And now the chief communicator is “Breaking Through,” the title of her first book about effective and innovative communications launching today. The full official title is “Breaking Through: Communicating to Open Minds, Move Hearts, and Change the World.”

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Max Colao, OncoVerity CEO

Tiny mul­ti­omics biotech se­cures for­mer J&J drug, new ex­ecs and new fi­nanc­ing

A new spinout from Belgium’s argenx seeks to give new life to a candidate once in-licensed to J&J.

OncoVerity announced Monday afternoon that it had in-licensed cusatuzumab from argenx. The biotech also appointed two new C-suite executives and secured a $30 million Series A round.

CEO Max Colao joins OncoVerity after working as Aurinia’s commercial chief, and stints at Alexion and Amgen. New CMO Clay Smith has been associate chief of the University of Colorado’s hematology division.

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