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.

Nick Bot­wood

“With this new in­di­ca­tion, Breyanzi is ap­proved to treat the broad­est re­lapsed or re­frac­to­ry large B cell lym­phoma pa­tient pop­u­la­tion,” Nick Bot­wood, BMS’ SVP of US med­ical af­fairs, told End­points News. “Breyanzi does rep­re­sent a sig­nif­i­cant ad­vance­ment of the cur­rent or pre­vi­ous treat­ment par­a­digm that has been in place for near­ly 30 years.”

Breyanzi was one of the stars of BMS’ $74 bil­lion Cel­gene buy­out back in 2019 and was first ap­proved last Feb­ru­ary to treat dif­fuse large B cell lym­phoma in pa­tients who have pre­vi­ous­ly re­ceived two pri­or rounds of sys­temic ther­a­py. At the time, BMS an­nounced a whole­sale price of $410,300. Last year, Breyanzi raked in $87 mil­lion, ac­cord­ing to the com­pa­ny’s Q4 re­sults.

The la­bel ex­pan­sion was based on piv­otal da­ta from two stud­ies, dubbed TRANS­FORM and PI­LOT. In the TRANS­FORM study, Breyanzi more than quadru­pled event-free sur­vival — de­fined as time un­til death, dis­ease pro­gres­sion, no re­sponse to ther­a­py or the need for ad­di­tion­al ther­a­py — com­pared to a place­bo (p<0.0001), ac­cord­ing to BMS. About 66% of pa­tients in the Breyanzi arm achieved a com­plete re­sponse, ver­sus 39% in the place­bo arm (p<0.0001).

Mean­while, in the sin­gle-arm PI­LOT study, 80% of pa­tients saw a re­sponse, while 54% of pa­tients achieved a CR. That study en­rolled 61 pa­tients with pri­ma­ry re­frac­to­ry or re­lapsed LB­CL who were not con­sid­ered can­di­dates for stem cell trans­plant.

BMS is look­ing to re­place the cur­rent stan­dard of care in this set­ting, which in­volves sal­vage chemother­a­py fol­lowed by high-dose chemo and a stem cell trans­plant. While stem cell trans­plants are be­com­ing more safe and ef­fec­tive, many sec­ond-line pa­tients can’t tol­er­ate sal­vage chemother­a­py. Ac­cord­ing to BMS, about half of pa­tients aren’t el­i­gi­ble for a trans­plant be­cause of their age or co­mor­bidi­ties, and among those who are el­i­gi­ble, on­ly a quar­ter are able to go through with it and see a long-term ben­e­fit.

“It’s a rel­a­tive­ly small pro­por­tion of the whole. So Breyanzi, it re­al­ly does pro­vide a sig­nif­i­cant new treat­ment op­tion for these pa­tients,” Bot­wood said.

Back in April, Gilead’s Kite won ap­proval for its CAR-T ri­val Yescar­ta in pa­tients with LB­CL who are re­frac­to­ry to first-line chemo, or who re­lapse with­in 12 months. Though it’s dif­fi­cult to com­pare da­ta across tri­als, the es­ti­mat­ed 18-month EFS rate for Yescar­ta was 41.5%, com­pared to 17% in the place­bo arm.

The com­pe­ti­tion here may come down to the safe­ty de­tails, as both drugs re­ceived a boxed warn­ing for cy­tokine re­lease syn­drome (CRS) and neu­ro­log­ic tox­i­c­i­ties. In the ZU­MA-7 study eval­u­at­ing Yescar­ta in the sec­ond line, Grade 3 or high­er CRS and neu­ro­log­ic events were ob­served in 7% and 25% of pa­tients, re­spec­tive­ly, ac­cord­ing to Kite.

In the PI­LOT and TRANS­FORM stud­ies, BMS said any-grade CRS was re­port­ed in 45% of pa­tients, and any-grade neu­ro­log­ic events were re­port­ed in 27%. Grade 3 CRS was re­port­ed in 1.3% of pa­tients, and Grade 3 neu­ro­log­ic events in 7% of pa­tients, ac­cord­ing to BMS.

“We did a pool analy­sis of the TRANS­FORM and the PI­LOT study, and ac­tu­al­ly the oc­cur­rences of cy­tokine re­lease syn­drome were gen­er­al­ly low-grade and most­ly re­solved quick­ly with stan­dard pro­to­cols,” Bot­wood said.

Al­so on Fri­day, a fed­er­al judge ruled against BMS’ mo­tion to dis­miss a case al­leg­ing it pur­pose­ly slow-rolled Breyanzi’s ap­proval to avoid pay­ing out $6.4 bil­lion in con­tin­gent val­ue rights (CVR) to Cel­gene share­hold­ers.

Up­on strik­ing a deal to ac­quire Cel­gene, BMS put $6.4 bil­lion in­to a CVR agree­ment that re­quired an FDA ap­proval for Zeposia, Breyanzi and Abec­ma, each by an es­tab­lished date. Af­ter the phar­ma gi­ant came up 36 days late on the Breyanzi dead­line, the CVR be­came worth­less.

Last June, UMB Bank filed suit against BMS, ac­cus­ing the com­pa­ny of pur­pose­ly de­lay­ing Breyanzi’s de­vel­op­ment to avoid the pay­outs.

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In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

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Ted Love, Global Blood Therapeutics CEO

Up­dat­ed: Pfiz­er scoops up Glob­al Blood Ther­a­peu­tics and its sick­le cell ther­a­pies for $5.4B

Pfizer is dropping $5.4 billion to acquire Global Blood Therapeutics.

Just ahead of the weekend, word got out that Pfizer was close to clinching a $5 billion buyout — albeit with other potential buyers still at the table. The pharma giant, flush with cash from Covid-19 vaccine sales, apparently got out on top.

The deal immediately swells Pfizer’s previously tiny sickle cell disease portfolio from just a Phase I program to one with an approved drug, Oxbryta, plus a whole pipeline that, if all approved, the company believes could make for a $3 billion franchise at peak.

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BREAK­ING: Math­ai Mam­men makes an abrupt ex­it as head of the big R&D group at J&J

In an after-the-bell shocker, J&J announced Monday evening that Mathai Mammen has abruptly exited J&J as head of its top-10 R&D group.

Recruited from Merck 5 years ago, where the soft spoken Mammen was being groomed as the successor to Roger Perlmutter, he had been one of the top-paid R&D chiefs in biopharma. His group spent $12 billion last year on drug development, putting it in the top 5 in the industry.

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No­vavax shares shred­ded as Covid vac­cine sales fall more than 90% in Q2

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

Pascal Soriot, AstraZeneca CEO (David Zorrakino/Europa Press via AP Images)

As­traZeneca and Dai­ichi Sankyo sprint to mar­ket af­ter FDA clears En­her­tu in just two weeks

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Uğur Şahin, BioNTech CEO (Kay Nietfeld/picture-alliance/dpa/AP Images)

De­spite falling Covid-19 sales, BioN­Tech main­tains '22 sales guid­ance

While Pfizer raked in almost $28 billion last quarter, its Covid-19 vaccine partner BioNTech reported a rise in total dose orders but a drop in sales.

The German biotech reported over $3.2 billion in revenue in Q2 on Monday, down from more than $6.7 billion in Q1, in part due to falling Covid sales. While management said last quarter that they anticipated a Covid sales drop — CEO Uğur Şahin said at the time that “the pandemic situation is still very much uncertain” — Q2 sales still missed consensus by 14%.

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FDA commissioner Rob Califf (Tom Williams/CQ Roll Call via AP Images)

With drug pric­ing al­most done, Con­gress looks to wrap up FDA user fee leg­is­la­tion

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Bernhardt Zeiher, outgoing Astellas CMO (Astellas)

Q&A: Astel­las' re­tir­ing head of de­vel­op­ment re­flects on gene ther­a­py deaths

For anyone who’s been following discussions about the safety alarms surrounding the adeno-associated viruses (AAV) commonly used to deliver gene therapy, Astellas should be a familiar name.

The Japanese pharma — which bought out Audentes Therapeutics near the end of 2019 and later built a gene therapy unit around the acquisition — rocked the field when it reported three patient deaths in a trial testing AT132, the lead program from Audentes designed to treat a rare muscle disease called X-linked myotubular myopathy (XLMTM).

When the company restarted the trial, it adjusted the dose and instituted a battery of other measures to try to prevent the same thing from happening again. But tragically, the first patient to receive the new regimen died just weeks after administration. The therapy remains under clinical hold, and just weeks ago, Astellas flagged another safety-related hold for a separate gene therapy candidate. In the process of investigating the deaths, the company has also taken flak about the way it disclosed information.

Big questions remain — questions that can have big implications about the future of AAV gene therapies.

Bernhardt Zeiher did not imagine any of it when he first joined Astellas as the therapeutic area leader in inflammation, immunology and infectious diseases. But his ascent to chief medical officer and head of development coincided almost exactly with Astellas’ big move into gene therapy, putting him often in the driver’s seat to grapple with the setbacks.

As Zeiher prepares to retire next month after a 12-year tenure — leaving the unfinished tasks to his successor, a seasoned cancer drug developer — he chatted with Endpoints News, in part, to discuss the effort to understand what happened, lessons learned and the criticism along the way.

The transcript has been lightly edited for length and clarity.

Endpoints: I want to also ask you a bit about the gene therapy efforts you’ve been working on. Astellas has really been at the forefront of discovering the safety concerns associated with AAV gene therapy. What’s that been like for you?

Zeiher: Well, I have to admit, it’s been a bit of a roller coaster. We acquired Audentes. Huge amount of enthusiasm. What we saw with AT132 — that was the lead program in XLMTM — was just remarkable efficacy. I mean, kids who went from being on ventilators, not able to eat for themselves, sit up, do things like that, to off ventilators, walking, you know, really — one investigator called it this Lazarus-like effect. It was just really dramatic efficacy. And then to have the safety events that occurred. So they actually occurred within that first year of the acquisition. So we had the three patient deaths. Me and my organization became very, very much involved. In fact, Ed Conner, who had been the chief medical officer, he left after some of the deaths, but I stepped in as the kind of acting chief medical officer, we had another chief medical officer who was involved, and then we had a fourth death, and I became acting again for a period of time.

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Sen­ate Dems cling to a sim­ple ma­jor­i­ty to pass some of the biggest drug pric­ing re­forms ever

The Pharmaceutical Research and Manufacturers of America — and their fleet of drug industry lobbyists on Capitol Hill — are known for never losing.

Whenever a big drug pricing bill comes up, an army of the industry group’s lobbyists descend onto the Hill and either smash it outright or dismantle it piece by piece.

But for perhaps the largest drug pricing reforms ever enacted, after more than a decade of Congress trying and failing to allow Medicare to negotiate prescription drug prices, those same lobbyists and their biopharma clients were dealt a stunning blow on Sunday afternoon.