Jean-Jacques Bienaimé. BioMarin via YouTube

Bil­lions on the line: Bio­Marin bus­tles past en­thused ri­val, plan­ning to launch world’s first he­mo­phil­ia A gene ther­a­py

Bio­Marin isn’t go­ing to let a ri­val’s suc­cess over the week­end get in the way of mak­ing a bee-line to the FDA with an im­per­fect, but pre­sentable, gene ther­a­py for he­mo­phil­ia A.

On Mon­day the biotech $BM­RN re­port­ed that its talks with the FDA and the EMA con­vinced ex­ecs to make a leap for an ac­cel­er­at­ed ap­proval with da­ta on just a hand­ful of pa­tients. And they’re hand­ing over Phase I/II and in­ter­im Phase III re­sults in Q4 to make their case.

That de­ci­sion was made de­spite a con­sid­er­able back­lash against the lat­est snap­shot of the da­ta, with wors­en­ing ef­fi­ca­cy over time and a low­er ini­tial re­sponse in their piv­otal tri­al — but ex­cel­lent bleed rates, so far. Bio­Marin says that with a break­through drug des­ig­na­tion in the USA and Eu­rope’s prime sta­tus, they have good rea­son to be­lieve they are on track to field the world’s first gene ther­a­py.

In­vestors ap­pear some­what skep­ti­cal though, with Bio­Marin shares down 2.4% in Mon­day af­ter­noon trad­ing.

Here’s the bet they’re mak­ing, out­lined in their lat­est state­ment:

Fac­tor VI­II lev­els sus­tained over a three-year pe­ri­od were suf­fi­cient to achieve strik­ing he­mo­sta­t­ic ef­fi­ca­cy. Fac­tor VI­II ex­pres­sion has en­tered a plateau phase where the rate of de­cline has sub­stan­tial­ly slowed, which could be in­dica­tive of durable, long-term ex­pres­sion.

Leerink’s Joseph Schwartz of­fers a bull­ish as­sess­ment of Bio­Marin’s gam­ble:

Based on BM­RN’s Ph.3 da­ta, the com­pa­ny met their pre-spec­i­fied cri­te­ria for ac­cel­er­at­ed ap­proval – 8 pts achiev­ing mean fac­tor VI­II/FVI­II lev­els above 40 IU/dL. With on­ly 17 pts (out of 20 pts) eval­u­at­ed so far, it is pos­si­ble that the re­main­ing 3 could pro­vide more con­fi­dence in Val­rox al­though it is not re­quired for ac­cel­er­at­ed ap­proval since BM­RN has al­ready met the bar. The com­pa­ny is fo­cused on get­ting Val­rox to mar­ket as soon as pos­si­ble by sub­mit­ting their fil­ing in 4Q19 based on their Ph.3 in­ter­im analy­sis and aims to com­plete GEN­Er8-1 (6E13 vg/kg) en­roll­ment in ear­ly fall 2019. As­sum­ing BM­RN could in­crease and op­ti­mize ef­fi­ca­cy — re­call, chro­mogenic mea­sures were high­er in Ph.1/2 at weeks 23-26 than Ph.3 (68 IU/dL mean/57 IU/dL me­di­an in Ph.1/2 vs 36 IU/dL mean/33 IU/dL me­di­an Ph.3) — we be­lieve that po­ten­tial stud­ies BM­RN may con­duct lat­er could fur­ther boost sales and in­crease Val­rox’s at­trac­tive­ness among he­mo­phil­ia A pts, es­pe­cial­ly as com­pet­ing pro­grams (i.e., SG­MO/PFE) ap­pear to be de­liv­er­ing com­pet­i­tive ef­fi­ca­cy.

Spark Ther­a­peu­tics $ONCE is wide­ly viewed as the run­ner up for now, while Roche strug­gles to com­plete its $4.3 bil­lion buy­out as soon as pos­si­ble. But Sang­amo/Pfiz­er gar­nered some care­ful sec­ond looks a few days ago as they post­ed bet­ter ef­fi­ca­cy and a fast re­sponse among 4 evalu­able pa­tients. That team al­so out­lined plans to make a leap for­ward on an ac­cel­er­at­ed path­way as they sought to catch up with the two fron­trun­ners.

Any stum­ble at this point could prove a set­back, but if they stay on track Sang­amo and Pfiz­er may set up a sit­u­a­tion where pa­tients can choose an im­per­fect gene ther­a­py or wait for a bet­ter one. And Bio­Marin has out­lined plans to charge in the range of $2 mil­lion to $3 mil­lion per treat­ment — with the ca­pa­bil­i­ty of earn­ing $10 bil­lion to $15 bil­lion a year — adding stick­er shock for pay­ers to the list of chal­lenges.

George Scangos (L) and Marianne De Backer

Pi­o­neer­ing biotech icon George Scan­gos hands in his re­tire­ment pa­pers — and this time it’s for re­al

George Scangos, one of the all-time great biotech CEOs, says the time has come to turn over the reins one last time.

The 74-year-old biotech legend spent close to three decades in a CEO post. The first was at Exelixis — which is still heavily focused on a drug Scangos advanced in the clinic. The second “retirement” was at Biogen, where he and his team were credited with a big turnaround with the now fading MS blockbuster Tecfidera. And the third comes at Vir, where he traded in his Big Biotech credentials for a marquee founder’s role back on the West Coast, hammering out a Covid-19 alliance with Hal Barron — then R&D chief at GSK — and breaking new ground on infectious diseases with some high-powered venture players.

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Jeanne Loring, director of the Center for Regenerative Medicine (Credit: Jamie Scott Lytle)

A stem cell pi­o­neer sent an ex­per­i­ment in­to space. Pa­tients are the next fron­tier

Last July, Jeanne Loring stood on a dirt road surrounded by Florida swampland and watched as a nearby SpaceX rocket blasted into the sky. The payload included a very personal belonging: cell clusters mimicking parts of her brain.

For more than two decades, Loring has been at the forefront of a stem cell field that always seems on the brink of becoming the next thing in medicine, but has been slow to lift off.

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FDA re­ports ini­tial 'no sig­nal' for stroke risk with Pfiz­er boost­ers, launch­es con­comi­tant flu shot study

The FDA hasn’t detected any potential safety signals, including for stroke, in people aged 65 years and older who have received Pfizer’s bivalent Covid booster, one senior official told members of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Thursday.

The update comes as the FDA and CDC investigate a “preliminary signal” that may indicate an increased risk of ischemic stroke in older Americans who received Pfizer’s updated shot.

FDA cuts off use for As­traZeneca’s Covid-19 ther­a­py Evusheld

The FDA has stopped use of another drug as a result of the new coronavirus variants. On Thursday, the agency announced that AstraZeneca’s antibody combo Evusheld, which was an important prevention option for many immunocompromised people and others, is no longer authorized.

The FDA said it made its decision based on the fact that Evusheld works on fewer than 10% of circulating variants.

Evusheld was initially given emergency authorization at the end of 2021. However, as Omicron emerged, so did studies that showed Evusheld might not work against the dominant Omicron strain. In October, the FDA warned healthcare providers that Evusheld was useless against the Omicron subvariant BA.4.6. It followed that up with another announcement earlier this month that it did not think Evusheld would work against the latest Omicron subvariant XBB.1.5.

In­vestor 'misalign­men­t' leads to tR­NA biotech's shut­ter­ing

A small biotech looking to carve a lane in the tRNA field has folded, an investor and a co-founder confirmed to Endpoints News.

Similar to Flagship’s Alltrna and other upstarts like Takeda-backed hC Bioscience, the now-shuttered Theonys was attempting to go after transfer RNA, seen as a potential Swiss Army knife in the broader RNA therapeutics space. The idea is that one tRNA drug could be used across a galaxy of disorders and diseases.

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Al Gianchetti, XyloCor CEO

Xy­lo­Cor wraps up PhII for heart dis­ease gene ther­a­py, plans for piv­otal tri­al

XyloCor Therapeutics says patients with heart disease who got its gene therapy could exercise for longer and had fewer chest pain attacks. The biotech announced it completed a Phase I/II trial of the gene therapy Thursday morning, and plans to move forward with a pivotal trial.

In the Phase II portion of the trial, 28 patients with angina (or chest pain) caused by coronary artery disease and who had no other treatment options were enrolled and were given the highest tested dose from the first part of the trial. Patients were followed for six months.

#JPM23: What's re­al­ly dri­ving the cost of health­care and drugs in 2023?

Executive Editor Drew Armstrong spoke with PhRMA CEO Steve Ubl, EmsanaRx CEO Greg Baker and ICER President Steve Pearson about how the debate over drug costs has changed (or not) in the last decade, the shifting payer landscape and why there seems to be so little movement on drug rebates. This transcript has been edited for brevity and clarity.

Drew Armstrong:

So first of all, thank you to everybody for being here and for our panel for being here. Incredibly excited to have this discussion on the cost of healthcare and drugs and what’s driving that. We’re here with Steve Ubl, the head of PhRMA. Thank you so much. Steve Pearson from ICER, and Greg Baker from EmsanaRx. I want to start this conversation with a little bit of a personal reminiscence. So about almost 10 years exactly. I was a reporter back in my previous job and I was covering drug pricing and Gilead had just launched their hepatitis C drug and I was having a conversation with another Steve over at Express Scripts and he made some comments essentially about how they intended to launch a price war over hepatitis C therapies.

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Pa­tient death spurs tri­al halt for Ma­gen­ta Ther­a­peu­tics

Magenta Therapeutics is pausing an early-stage clinical trial after a patient died. The death was deemed to be possibly related to its drug, MGTA-117.

The biotech said the pause of the Phase I/II trial is voluntary and gives it time to review all available data before deciding what to do next. It’s also reported the known information to the FDA.

The dose-escalation trial was designed to test whether MGTA-117, an antibody-drug conjugate, could serve as a more targeted alternative to high-intensity chemotherapy as a conditioning agent for cancer patients who are set to receive a stem cell transplant. It recruited patients with relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome.

In a win for Re­gen­eron, No­var­tis' sy­ringe for AMD drug de­clared 'un­patentable'

Regeneron has won a patent case against Swiss pharma giant Novartis over the delivery system for its eye drug Eylea.

The US Patent Trial and Appeal Board ruled that Novartis’ pre-filled syringe for injecting its eye medication Lucentis was “unpatentable” and handed the victory to Regeneron and its AMD drug Eylea.

In the initial complaint in 2020, Novartis alleged to the US International Trade Commission that certain pre-filled syringes for the intravitreal injection, and ultimately Regeneron’s delivery system for Eylea, were infringing on Novartis’ patent. Regeneron filed a petition to review Novartis’ claims in 2021.