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. 

As­traZeneca trum­pets the 'mo­men­tous' da­ta they found for Tagris­so in an ad­ju­vant set­ting for NSCLC — but many of the ex­perts aren’t cheer­ing along

AstraZeneca is rolling out the big guns this evening to provide a salute to their ADAURA data on Tagrisso at ASCO.

Cancer R&D chief José Baselga calls the disease-free survival data for their drug in an adjuvant setting of early stage, epidermal growth factor receptor-mutated NSCLC patients following surgery “momentous.” Roy Herbst, the principal investigator out of Yale, calls it “transformative.”

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Pablo Legorreta, founder and CEO of Royalty Pharma AG, speaks at the annual Milken Institute Global Conference in Beverly Hills, California (Patrick T. Fallon/Bloomberg via Getty Images)

Cap­i­tal­iz­ing Pablo: The world’s biggest drug roy­al­ty buy­er is go­ing pub­lic. And the low-key CEO di­vulges a few se­crets along the way

Pablo Legorreta is one of the most influential players in biopharma you likely never heard of.

Over the last 24 years, Legorreta’s Royalty Pharma group has become, by its own reckoning, the biggest buyer of drug royalties in the world. The CEO and founder has bought up a stake in a lengthy list of the world’s biggest drug franchises, spending $18 billion in the process — $2.2 billion last year alone. And he’s become one of the best-paid execs in the industry, reaping $28 million from the cash flow last year while reserving 20% of the cash flow, less expenses, for himself.

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Ab­b­Vie wins an ap­proval in uter­ine fi­broid-as­so­ci­at­ed heavy bleed­ing. Are ri­vals My­ovant and Ob­sE­va far be­hind?

Women expel on average about 2 to 3 tablespoons of blood during their time of the month. But with uterine fibroids, heavy bleeding is typical — a third of a cup or more. Drugmakers have been working on oral therapies to try and stem the flow, and as expected, AbbVie and their partners at Neurocrine Biosciences are the first to make it across the finish line.

Known chemically as elagolix, the drug is already approved as a treatment for endometriosis under the brand name Orilissa. It targets the GnRH receptor to decrease the production of estrogen and progesterone.

Fabrice Chouraqui, Cellarity CEO-partner (LinkedIn)

Drug de­vel­op­er, Big Phar­ma com­mer­cial ex­ec, now an up­start biotech chief — Fab­rice Chouraqui is ready to try some­thing new as a ‘CEO-part­ner’ at Flag­ship

Fabrice Chouraqui’s career has taken some big twists along his life journey. He got his PharmD at Université Paris Descartes and jumped into the drug development game for a bit. Then he took a sharp turn and went back to school to get his MBA at Insead before returning to pharma on the commercial side.

Twenty years later, after steadily rising through the ranks and journeying the globe to nab a top job as president of US pharma for the Basel-based Novartis, Chouraqui exited in another career switch. And now he’s headed into a hybrid position as a CEO-partner at Flagship, where he’ll take a shot at leading Cellarity — one of the VC’s latest paradigm-changing companies of the groundbreaking model that aspires to deliver a new platform to the world of drug R&D.

David Chang, Allogene CEO (Jeff Rumans)

Head­ed to PhII: Al­lo­gene CEO David Chang com­pletes a pos­i­tive ear­ly snap­shot of their off-the-shelf CAR-T pi­o­neer

Allogene CEO David Chang has completed the upbeat first portrait of the biotech’s off-the-shelf CAR-T contender ALLO-501 at virtual ASCO today, keeping all eyes on a drug that will now try to go on to replace the first-wave personalized pioneers he helped create.

The overall response rate outlined in Allogene’s abstract for treatment-resistant patients with non-Hodgkin lymphoma slipped a little from the leadup, but if you narrow the patient profile to treatment-naïve patients — removing the 3 who had previous CAR-T therapy who didn’t respond, leaving 16 — the ORR lands at 75% with a 44% complete response rate. And 9 of the 12 responders remained in response at the data cutoff, offering a glimpse on durability that still has a long way to go before it can be completely nailed down.

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Paul Hudson, Sanofi CEO (Getty Images)

Sanofi CEO Paul Hud­son has $23B burn­ing a hole in his pock­et. And here are some hints on how he plans to spend that

Sanofi has reaped $11.1 billion after selling off a big chunk of its Regeneron stock at $515 a share. And now everyone on the M&A side of the business is focused on how CEO Paul Hudson plans to spend it.

After getting stung in France for some awkward politicking — suggesting the US was in the front of the line for Sanofi’s vaccines given American financial support for their work, versus little help from European powers — Hudson now has the much more popular task of managing a major cash cache to pull off something in the order of a big bolt-on. Or two.

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Roger Perlmutter, Merck R&D chief (YouTube)

UP­DAT­ED: Backed by BAR­DA, Mer­ck jumps in­to Covid-19: buy­ing out a vac­cine, part­ner­ing on an­oth­er and adding an­tivi­ral to the mix

Merck execs are making a triple play in a sudden leap into the R&D campaign against Covid-19. And they have more BARDA cash backing them up on the move.

Tuesday morning the pharma giant simultaneously announced plans to buy an Austrian biotech that has been working on a preclinical vaccine candidate, added a collaboration on another vaccine with the nonprofit IAVI and inked a deal with Ridgeback Biotherapeutics on an early-stage antiviral.

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As­traZeneca’s $7B ADC suc­ceeds where Roche failed, im­prov­ing sur­vival in gas­tric can­cer

Another day, another win for Enhertu.

The antibody-drug conjugate AstraZeneca promised up-to $7 billion to partner on has had a quite a few months, beginning with splashy results in a Phase II breast cancer trial, a rapid approval and, earlier this month, breakthrough designations in both non-small cell lung cancer and gastric cancer.

Now, at ASCO, the British pharma and their Japanese partner, Daiichi Sankyo, have shown off the data that led to the gastric cancer designation, which they’ll take back to the FDA. In a pivotal, 187-person Phase II trial, Enhertu shrunk tumors in 42.9% of third-line patients with HER2-positive stomach cancer, compared with 12.5% in a control arm where doctors prescribed their choice of therapy. Progression-free survival was 5.4 months for Enhertu compared to 3.5 months for the control.

Once a gem, now just a rock, Take­da punts PhI­II IBD drug as ri­vals mus­cle ahead

Back in 2016, when then-Shire CEO Flemming Ørnskov picked up a promising clinical-stage IBD drug from Pfizer, the Boston-based biotech dubbed it SHP647 and moved it into the gem section of the pipeline, with rosy expectations of registration-worthy Phase III data ahead.

This was a drug that the EC wanted Takeda to commit to selling off before it gave their blessing to its acquisition of Shire, to settle some deep-seated concerns revolving around the potential market overlap with their blockbuster rival Entyvio. And Takeda, which took on a heavy debt load to buy Shire, clearly wanted the cash to pay down debt.