Point­ing to a cure, Bio­Marin re­ports im­pres­sive tri­al re­sults for he­mo­phil­ia A gene ther­a­py

Bio­Marin says it nailed down hard ev­i­dence that its gene ther­a­py for he­mo­phil­ia A demon­strat­ed a high chance of restor­ing pa­tients’ nat­ur­al clot­ting abil­i­ties, re­duc­ing or elim­i­nat­ing bleed­ing episodes and point­ing them down the road to a nor­mal life. And com­pa­ny $BM­RN in­ves­ti­ga­tors say they are now hus­tling BMN 270 in­to a Phase IIb study that could be used to gain an ac­cel­er­at­ed ap­proval for a po­ten­tial block­buster.

Nine pa­tients re­ceived a sin­gle treat­ment with the gene ther­a­py, 7 at the high­est dose. The treat­ment us­es a be­nign vi­ral vec­tor to de­liv­er a miss­ing gene need­ed to pro­duce fac­tor VI­II, which is re­quired to spur clot­ting. The da­ta were pre­sent­ed at the an­nu­al meet­ing of the World Fed­er­a­tion of He­mo­phil­ia. Bio­Marin not­ed that:

(S)ix of sev­en pa­tients had Fac­tor VI­II lev­els above 50%, as a per­cent­age cal­cu­lat­ed based on the num­bers of In­ter­na­tion­al Units per deciliter of plas­ma (IU/dL), and the sev­enth was above 10%. In ad­di­tion, four pa­tients who have been fol­lowed the longest had a mean Fac­tor VI­II lev­el of 146% at their 20 week vis­it. Two pa­tients with Fac­tor VI­II lev­els above 200% had no un­ex­pect­ed events or need for med­ical in­ter­ven­tion. For the sev­en pa­tients at the high dose, the me­di­an an­nu­al­ized bleed­ing rate mea­sured from day of gene trans­fer to da­ta cut of ob­ser­va­tion pe­ri­od fell to 5 from 20.

In ad­di­tion, the in­ves­ti­ga­tors re­port­ed no se­ri­ous safe­ty is­sues in the study, with pa­tients ta­per­ing off steroid use with­out the kind of liv­er tox is­sues that could scut­tle the work.

Hen­ry Fuchs, CMO at Bio­Marin

The re­sults from the study were “way be­yond our dreams and ex­pec­ta­tions,” says Hank Fuchs, the chief med­ical of­fi­cer at Bio­Marin, cit­ing the in­ves­ti­ga­tors and on­look­ers who have been track­ing this study.

This is the on­ly he­mo­phil­ia A pro­gram in the clin­ic that Fuchs knows of, and he tells me that the once-off ther­a­py “has the po­ten­tial to change peo­ple’s lives.”

“We have con­sid­er­able in­ter­est in mov­ing quick­ly,” adds the R&D chief, adding that the com­pa­ny wants to pre­serve its lead. But he’s not quite ready to say when the com­pa­ny will have the da­ta from the next study need­ed to pur­sue a fast ap­proval.

Shares of Bio­Marin, which has tapped this ther­a­py as one of its top prospec­tive pro­grams in the pipeline, spiked 6% on the news Wednes­day af­ter­noon.

That amounts to a big win for Bio­Marin, which has been buf­fet­ed by re­cent set­backs, in­clud­ing the FDA’s re­jec­tion of its Duchenne mus­cu­lar dy­s­tro­phy drug dris­apersen. Bio­Marin scrapped that pro­gram and three oth­ers af­ter the EMA al­so scorned its ap­pli­ca­tion.

There are a num­ber of gene ther­a­py pro­grams in the works for he­mo­phil­ia, in­clud­ing one at Bio­gen $BI­IB. Spark Ther­a­peu­tics $ONCE, which has the most ad­vanced gene ther­a­py pro­gram in the U.S., has a pre­clin­i­cal pro­gram for he­mo­phil­ia A and a clin­i­cal ef­fort un­der­way for he­mo­phil­ia B; same for uniQure $QURE. And Sang­amo $SG­MO just pre­sent­ed pre­clin­i­cal ev­i­dence to back its pro­gram.

“These da­ta pro­vide strong proof of con­cept ev­i­dence that restora­tion of clot­ting func­tion may be achieved by gene ther­a­py,” said John Pasi, a pro­fes­sor of haemosta­sis and throm­bo­sis at Barts and the Lon­don School of Med­i­cine and Den­tistry and pri­ma­ry in­ves­ti­ga­tor for the BMN 270 Phase 1/2 clin­i­cal tri­al.  “For the first time, pa­tients have rea­son to hope to avoid bleed­ing and the op­por­tu­ni­ty to live a nor­mal life.”

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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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.

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.

Bris­tol My­ers claims win with CAR-T ther­a­py Breyanzi in leukemia

Bristol Myers Squibb is looking to expand Breyanzi into more indications — and the pharma’s newest data readout makes progress on that front.

The Big Pharma put out word Thursday that the CAR-T cell therapy met the primary endpoint of complete response rate compared to historical control in a subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) that were refractory to a BTK inhibitor and pretreated with a BCL-2 inhibitor.

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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Vu Truong, Aridis Pharmaceuticals CEO (Aridis/Nasdaq)

Aridis' mon­o­clon­al an­ti­body fails PhI­II, but plans for sec­ond tri­al any­way

Aridis Pharmaceuticals’ monoclonal antibody missed the bar in a Phase III test in ventilator-associated pneumonia caused by the gram-positive bacteria S. aureus, the company announced Wednesday. 

But Aridis is planning for a second Phase III study anyway once it discusses the findings with the FDA and the European Medicines Agency. Execs blamed recruitment challenges stemming from Covid-19 and Russia’s invasion of Ukraine for the miss, cutting their enrollment target in half.

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.