Even at $2M+, ICER calls blue­bird's po­ten­tial gene ther­a­py for blood dis­or­der 'su­pe­ri­or' to stan­dard of care

The In­sti­tute for Clin­i­cal and Eco­nom­ic Re­view, a drug pric­ing watch­dog, gave a mea­sured thumbs up on Thurs­day morn­ing to blue­bird’s po­ten­tial­ly ex­pen­sive new gene ther­a­py for a rare but de­bil­i­tat­ing blood dis­or­der, which will go be­fore an FDA ad­vi­so­ry com­mit­tee next Fri­day.

While blue­bird raised some stick­er-shock eye­brows with its pro­posed price of $2.1 mil­lion per treat­ment course of what’s known as beti-cel, ICER said pre­vi­ous­ly in April and again to­day that the ther­a­py would be cost-ef­fec­tive, as long as there’s an 80% pay­back op­tion for pa­tients who do not achieve and main­tain trans­fu­sion in­de­pen­dence over a five-year pe­ri­od.

For the 1,000-1,500 peo­ple in the US liv­ing with trans­fu­sion de­pen­dent tha­lassemia, cur­rent treat­ment reg­i­mens in­clude life­long reg­u­lar blood trans­fu­sions and iron chela­tion ther­a­py to avert the con­se­quences of iron over­load, ac­cord­ing to ICER.

And un­til re­cent­ly, the on­ly cu­ra­tive op­tion for TDT was al­lo­gene­ic hematopoi­et­ic stem cell trans­plan­ta­tion (HSCT) from a sib­ling or oth­er matched donor. But ICER ex­plains how HSCT re­quires high dos­es of con­di­tion­ing chemother­a­py and places the re­cip­i­ent at risk of com­pli­ca­tions, like graft vs. host dis­ease, and find­ing an HSCT match is dif­fi­cult as few­er than 25% of pa­tients have ac­cess to a suit­able match.

Mean­while, Phase III tri­als of beti-cel showed trans­fu­sion in­de­pen­dence was achieved in 89% of the pa­tients who re­ceived the gene ther­a­py, ICER said.

Still, ICER’s lat­est re­vised re­port ex­plained how there are dura­bil­i­ty and oth­er ques­tion marks to look out for with beti-cel too. And by Tues­day or Wednes­day of next week, the FDA will re­lease its own eval­u­a­tion of the da­ta on beti-cel, and blue­bird’s oth­er lentivi­ral gene ther­a­py, eli-cel, which tar­gets a meta­bol­ic con­di­tion called cere­bral adrenoleukody­s­tro­phy and will come be­fore the same ad­comm on Thurs­day.

“Be­cause of the ques­tions about the dura­bil­i­ty of clin­i­cal ben­e­fit, as well as po­ten­tial risks from gene ther­a­py, we judge that the ev­i­dence demon­strates that beti-cel is su­pe­ri­or over­all to the cur­rent stan­dard of care, but the mag­ni­tude of that over­all net health ben­e­fit is less cer­tain, rang­ing from in­cre­men­tal to sub­stan­tial (B+),” ICER said, adding:

Tra­di­tion­al cost-ef­fec­tive­ness mod­el­ing finds that this new treat­ment meets com­mon­ly ac­cept­ed val­ue thresh­olds at a cu­mu­la­tive price of $2.1 mil­lion with an 80% pay­back op­tion for pa­tients who do not achieve and main­tain trans­fu­sion in­de­pen­dence over a five-year pe­ri­od.

The ad­comm for beti-cel al­so marks an­oth­er defin­ing mo­ment for the gene ther­a­py field, William Blair an­a­lysts not­ed pre­vi­ous­ly, as it’s the first time the Cel­lu­lar, Tis­sue, and Gene Ther­a­pies Ad­vi­so­ry Com­mit­tee has met to dis­cuss a prod­uct since Spark Ther­a­peu­tics’ (now owned by Roche) Lux­tur­na in Oc­to­ber 2017.

It will al­so be a defin­ing mo­ment for blue­bird, which has seen a long road for both beti-cel and eli-cel, and in April an­nounced lay­offs of 30% of its work­force to save it­self be­fore the FDA de­cides the fate of two of its gene ther­a­pies in Au­gust and Sep­tem­ber.

In Feb­ru­ary 2021, blue­bird vol­un­tar­i­ly paused two stud­ies for its sick­le cell gene ther­a­py af­ter two pa­tients un­ex­pect­ed­ly de­vel­oped can­cer and a can­cer-like case, re­sult­ing in a four-month clin­i­cal hold. Blue­bird lat­er demon­strat­ed that the can­cer case was un­re­lat­ed to the virus­es used in its gene ther­a­py and that the can­cer-like case was a mis­di­ag­no­sis. But the pause re­sult­ed in a de­layed Eu­ro­pean launch for beti-cel, which us­es the same lentivi­ral de­liv­ery mech­a­nism.

In Au­gust 20021, an­oth­er can­cer-like case popped up in a tri­al for eli-cel, forc­ing blue­bird to hit the brakes on a study. That case, blue­bird said, did ap­pear linked to the gene ther­a­py. In the same an­nounce­ment, blue­bird said it would stop sell­ing its gene ther­a­pies in Eu­rope af­ter fail­ing to reach pric­ing agree­ments with gov­ern­ments.

Ob­servers spec­u­lat­ed blue­bird did not want to charge less for the drug, brand­ed Zyn­te­glo in Eu­rope, for fear it would ul­ti­mate­ly have to low­er prices in the US. In Ger­many, the on­ly coun­try for which blue­bird has dis­closed de­tails, au­thor­i­ties of­fered $790,000 for the one-time treat­ment, with the pay­out mov­ing to $950,000 if the ther­a­py was still work­ing af­ter five years. But blue­bird want­ed some­thing in the range of $1.8 mil­lion af­ter that time pe­ri­od.

But the dire sit­u­a­tion for the com­pa­ny has come in­to clear­er view this year when blue­bird said in a quar­ter­ly fil­ing its cash prob­lems “raise sub­stan­tial doubt re­gard­ing its abil­i­ty to con­tin­ue as a go­ing con­cern” in the com­ing year. The CFO re­signed the same day.

Scoop: Boehringer qui­et­ly shut­ters a PhII for one of its top drugs — now un­der re­view

Boehringer Ingelheim has quietly shut down a small Phase II study for one of its lead drugs.

The private pharma player confirmed to Endpoints News that it had shuttered a study testing spesolimab as a therapy for Crohn’s patients suffering from bowel obstructions.

A spokesperson for the company tells Endpoints:

Taking into consideration the current therapeutic landscape and ongoing clinical development programs, Boehringer Ingelheim decided to discontinue our program in Crohn’s disease. It is important to note that this decision is not based on any safety findings in the clinical trials.

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Alex­ion puts €65M for­ward to strength­en its po­si­tion on the Emer­ald Isle

Ireland has been on a roll in 2022, with several large pharma companies announcing multimillion-euro projects. Now AstraZeneca’s rare disease outfit Alexion is looking to get in on the action.

Alexion on Friday announced a €65 million ($68.8 million) investment in new and enhanced capabilities across two sites in the country, including at College Park in the Dublin suburb of Blanchardstown and the Monksland Industrial Park in the central Irish town of Athlone, according to the Industrial Development Agency of Ireland.

Fed­er­al judge de­nies Bris­tol My­er­s' at­tempt to avoid Cel­gene share­hold­er law­suit

Some Celgene shareholders aren’t happy with how Bristol Myers Squibb’s takeover went down.

On Friday, a New York federal judge ruled that they have a case against the pharma giant, denying a request to dismiss allegations that it purposely slow-rolled Breyanzi’s approval to avoid paying out $6.4 billion in contingent value rights (CVR).

When Bristol Myers put down $74 billion to scoop up Celgene back in 2019, liso-cel — the CAR-T lymphoma treatment now marketed as Breyanzi — was supposedly one of the centerpieces of the deal. After going back and forth on negotiations for about six months, BMS put $6.4 billion into a CVR agreement that required an FDA approval for Zeposia, Breyanzi and Abecma, each by an established date.

No stranger to gene ther­a­py woes, Astel­las runs in­to an­oth­er safe­ty-re­lat­ed clin­i­cal hold

Astellas Pharma, which has been at the forefront of uncovering the risks associated with gene therapies delivered by adeno-associated viruses, must take another safety alarm head-on.

The FDA has slapped a clinical hold on Astellas’ Phase I/II trial of a gene therapy candidate for late-onset Pompe disease, after investigators flagged a serious case of peripheral sensory neuropathy.

It marks the latest in a streak of setbacks Astellas has encountered since making a splashy entry into the gene therapy space with its $3 billion buyout of Audentes. But the lead program, AT132 for the treatment of X-linked myotubular myopathy (XLMTM), had to be halted more than once after a total of four patients died in the trial — and the scientific community still doesn’t have all the answers of what caused the deaths.

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Linda Marbán, Capricor CEO

Capri­cor hits pri­ma­ry end­point in Duchenne ex­ten­sion study, ready­ing its FDA pitch

It has been a very bumpy ride for Capricor Therapeutics over the past several years, including a halted J&J partnership and venture into penny stock status. However, the latest news from the San Diego-based biotech shows that its experimental Duchenne drug may be a durable, long-term treatment.

The company posted the one-year results from its open-label extension study for their candidate dubbed CAP-1002. The extension from its Phase II study, named HOPE-2, was conducted in boys and young men with later-stage Duchenne muscular dystrophy who paused and then resumed treatment after a year. Researchers measured patients in the one-year follow-up against the original study’s treatment arm effect and in two subsets of the original placebo group.

AstraZeneca's new Evusheld direct to consumer campaign aims to reach more immunocompromised patients.

As­traZeneca de­buts first con­sumer cam­paign for its Covid-19 pro­phy­lac­tic Evusheld — and a first for EUA drugs

AstraZeneca’s first consumer ad for Evusheld is also a first for drugs that have been granted emergency use authorizations during the pandemic.

The first DTC ad for a medicine under emergency approval, the Evusheld campaign launching this week aims to raise awareness among immunocompromised patients — and spur more use.

Evusheld nabbed emergency authorization in December, however, despite millions of immunocompromised people looking for a solution and now more widespread availability of the drug.

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Am­gen takes next step with its Chi­na am­bi­tions, out-li­cens­ing drugs to Fo­s­un Phar­ma

In a bid to increase its market share in China, Amgen has agreed to a partnership with a Shanghai biotech — a collaboration and out-licensing agreement for two of its drugs.

Amgen and Fosun Pharma announced a deal Monday in a bid to increase Amgen’s presence in the country. The stated goal so far is to commercialize Amgen’s blockbuster psoriasis drug Otezla alongside Parsabiv, a drug for secondary hyperparathyroidism in adults with chronic kidney disease and on a specific type of dialysis.

As court case looms, Bris­tol My­ers touts la­bel ex­pan­sion for Breyanzi

As Bristol Myers Squibb braces for a court battle over a costly delay — at least for Celgene shareholders — for its CAR-T lymphoma treatment Breyanzi, the pharma giant is touting a label expansion in the second-line setting.

Breyanzi, also known as liso-cel, snagged a win on Friday in adults with large B-cell lymphoma (LBCL) who: don’t respond to chemotherapy, or relapse within 12 months; don’t respond or relapse after 12 months; or are not eligible for hematopoietic stem cell transplant after chemo due to their age or comorbidities.

State bat­tles over mifepri­s­tone ac­cess could tie the FDA to any post-Roe cross­roads

As more than a dozen states are now readying so-called “trigger” laws to kick into effect immediate abortion bans following the overturning of Roe v. Wade on Friday, these laws, in the works for more than a decade in some states, will likely kick off even more legal battles as states seek to restrict the use of prescription drug-based abortions.

Since Friday’s SCOTUS opinion to overturn Americans’ constitutional right to an abortion after almost 50 years, reproductive rights lawyers at Planned Parenthood and other organizations have already challenged these trigger laws in Utah and Louisiana. According to the Guttmacher Institute, other states with trigger laws that could take effect include Arkansas, Idaho, Kentucky, Mississippi, Missouri, North Dakota, Oklahoma, South Dakota, Tennessee, Texas, and Wyoming.

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