FDA lets blue­bird re­sume tri­als for sick­le cell gene ther­a­py af­ter can­cer scare, but big ques­tions linger over field

Blue­bird bio an­nounced that the FDA has lift­ed its holds on clin­i­cal tri­als for their gene ther­a­pies for sick­le dis­ease and be­ta-tha­lassemia, end­ing a 4-month saga that be­gan af­ter the biotech re­port­ed that two pa­tients had come down with can­cer and a can­cer-like con­di­tion.

Reg­u­la­tors were con­cerned that the cas­es may have been trig­gered by the virus blue­bird us­es to de­liv­er a healthy gene for he­mo­glo­bin in­to pa­tients with rare blood dis­or­ders, as had hap­pened in a 2004 gene ther­a­py tri­al that re­lied on a sim­i­lar virus. Blue­bird large­ly al­layed those con­cerns in March, when they re­leased a ge­net­ic analy­sis show­ing that the virus didn’t in­ter­fere with the pa­tient’s DNA in a way like­ly to trig­ger can­cer, but ex­perts say the cas­es have broad­ly raised con­cerns about the risks any of the more than half dozen of sick­le dis­ease gene ther­a­pies now in clin­i­cal de­vel­op­ment may pose.

Ak­shay Shar­ma, a pe­di­atric bone mar­row spe­cial­ist at St. Jude, said doc­tors al­ready knew peo­ple with sick­le cell dis­ease are at greater risk of de­vel­op­ing leukemia. But the cas­es high­light­ed how any form of ge­net­ic ma­nip­u­la­tion — in­clud­ing the CRISPR-based ap­proach­es Ver­tex, No­var­tis, Beam and oth­ers are pur­su­ing — could ex­ac­er­bate that pre­dis­po­si­tion.

Ak­shay Shar­ma

“We def­i­nite­ly need more re­search to un­der­stand ex­act­ly what is this pre­dis­po­si­tion, and once we know it, on­ly then will we sat­is­fac­to­ri­ly an­swer this ques­tion: Is it safe or not?” Shar­ma, who has served as an in­ves­ti­ga­tor on gene ther­a­py tri­als, told End­points News. “And I think the an­swer may be in the mid­dle. Per­haps these ge­net­ic ther­a­pies are safe for most pa­tients, but some pa­tients are at greater risk.”

For blue­bird, the hold was an­oth­er in a se­ries of set­backs the Cam­bridge biotech has faced in the years since they first showed da­ta from a hand­ful of pa­tients sug­gest­ing that their gene ther­a­py can be a func­tion­al cure for sick­le cell dis­ease. Un­able to prove to the FDA they could man­u­fac­ture their prod­uct safe­ly at scale, they’ve re­peat­ed­ly pushed back the date for fil­ing for ap­proval.

Most re­cent­ly, they pushed their time­line in­to late 2022, al­though that was be­fore the FDA hold came down. The de­lays have al­lowed Ver­tex and CRISPR Ther­a­peu­tics to catch up with a gene edit­ing ap­proach that en­tered the clin­ic five years lat­er. The two now be­lieve they will be first-to-mar­ket with a sick­le cell cure, which could pro­vide a ma­jor com­mer­cial ad­van­tage.

Nev­er­the­less, the FDA de­ci­sion re­newed in­vestor faith in blue­bird’s path ahead. The stock $Blue rose 6% in pre-mar­ket trad­ing, from $30.92 to $33.00.

In Feb­ru­ary, blue­bird an­nounced that a sick­le cell pa­tient who re­ceived their gene ther­a­py five years pri­or was di­ag­nosed with acute myeloid leukemia. A sec­ond, they said, had been di­ag­nosed with a sus­pect­ed case of myelodys­plas­tic syn­drome, a can­cer-like dis­ease that oc­curs in the bone mar­row. They lat­er said the lat­ter case was in fact a mis­di­ag­nosed case of trans­fu­sion-de­pen­dent ane­mia.

Al­though blue­bird’s analy­sis showed that the virus blue­bird us­es — a re-en­gi­neered form of HIV, called a lentivirus — didn’t in­ter­fere with genes known to cause can­cer, Shar­ma said the ther­a­py could have el­e­vat­ed the pa­tients’ risks in oth­er ways. It could have made more sub­tle ge­net­ic al­ter­ations, or the chemother­a­py “con­di­tion­ing” reg­i­ment pa­tients pri­or to the ther­a­py could have made them more sus­cep­ti­ble.

Af­ter a pa­tient who re­ceived blue­bird’s ther­a­py was di­ag­nosed with myelodys­plas­tic syn­drome in 2018, the com­pa­ny at­trib­uted it to the chemother­a­py.

Re­cent stud­ies, Shar­ma not­ed, have linked the risk of leukemia af­ter a trans­plant to spe­cif­ic ge­net­ic mu­ta­tions. Re­searchers need to de­vel­op meth­ods of screen­ing for pa­tients who have that mu­ta­tion and po­ten­tial­ly oth­er mu­ta­tions that could put them at greater risk and quan­ti­fy pre­cise­ly how high that risk is. They will al­so need ways of min­i­miz­ing those risks, such as by de­vel­op­ing safer al­ter­na­tives to chemother­a­py — a task com­pa­nies such as Ma­gen­ta and Jasper Ther­a­peu­tics are now work­ing on.

He em­pha­sized that it would not be a prob­lem just for blue­bird but to any of the near­ly dozen at­tempts to cure sick­le cell dis­ease now at or near the clin­ic.

“If some­body has a pre­dis­po­si­tion,” he said, “any type of ge­net­ic al­ter­ation or ex­po­sure to chemother­a­py could ac­cel­er­ate that and lead to leukemia.”

A new era of treat­ment: How bio­mark­ers are chang­ing the way we think about can­cer

AJ Patel was recovering from a complicated brain surgery when his oncologist burst into the hospital room yelling, “I’ve got some really great news for you!”

For two years, Patel had been going from doctor to doctor trying to diagnose his wheezing, only to be dealt the devastating news that he had stage IV lung cancer and only six months to live. And then they found the brain tumors.

“What are you talking about?” Patel asked. He had never seen an oncologist so happy.

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David Ricks, Eli Lilly CEO (David Paul Morris/Bloomberg via Getty Images)

Eli Lil­ly set to in­vest $2.1B in home state man­u­fac­tur­ing boost

Eli Lilly is looking to expand its footprint in its home Hoosier State by making a major investment in manufacturing.

The pharma is investing $2.1 billion in two new manufacturing sites at Indiana’s LEAP Lebanon Innovation and Research District in Boone County, northwest of Lilly’s headquarters in Indianapolis.

The two new facilities will expand Lilly’s manufacturing network for active ingredients and new therapeutic modalities, including genetic medicines, according to a press release.

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US sees spike in Paxlovid us­age as Mer­ck­'s mol­nupi­ravir and As­traZeneca's Evusheld are slow­er off the shelf

New data from HHS show that more than 162,000 courses of Pfizer’s Covid-19 antiviral Paxlovid were administered across the US over the past week, continuing a streak of increased usage of the pill, and signaling not only rising case numbers but more awareness of how to access it.

In comparison to this week, about 670,000 courses of the Pfizer pill have been administered across the first five months since Paxlovid has been on the US market, averaging about 33,000 courses administered per week in that time.

Almirall is tapping artificial intelligence on behalf of its sales force for insights and efficiencies. (via Shutterstock)

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Dermatology specialty pharma Almirall is making its sales reps smarter. Not with extra training or educational courses, but instead with artificial intelligence tools.

It began a soft launch of a sales rep AI and machine learning platform it calls Polaris last August in one of its 7 US coverage regions. The platform from Aktana gathers information from across Almirall internal sources and external ones – such as claims and prescribing data – to generate insights for reps. Now, instead of spending hours prepping for a sales call, Polaris can generate details about a physician’s preferences, past behaviors and prescription habits for reps in minutes, said Almirall head of commercial operations Vincent Cerio.

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Pfiz­er and CD­MOs ramp up Paxlovid man­u­fac­tur­ing with Kala­ma­zoo plant ex­pan­sion lead­ing the way

As the Covid-19 pandemic continues to evolve, pharma companies and manufacturers are exploring how to step up production on antivirals.

Pfizer is planning to expand its Kalamazoo-area facility to increase manufacturing capabilities for the oral Covid-19 antiviral Paxlovid, according to a report from Michigan-based news site MLive. The expansion of the facility, which serves as Pfizer’s largest manufacturing location, is expected to create hundreds of “high-skilled” STEM jobs, MLive reported. No details about the project’s cost and timeline have been released, but according to MLive, Pfizer will announce the details of the expansion at some point in early June.

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FDA spells out the rules and re­stric­tions for states seek­ing to im­port drugs from Cana­da

The FDA is offering more of an explanation of the guardrails around its program that may soon allow states to import prescription drugs in some select circumstances from Canada, but only if such imports will result in significant cost reductions for consumers.

While the agency has yet to sign off on any of the 5 state plans in the works so far, and PhRMA’s suit to block the Trump-era rule allowing such imports is stalled, the new Q&A guidance spells out the various restrictions that states will have to abide by, potentially signaling that a state approval is coming.

Greg Mayes, Antios Therapeutics CEO

An­tios' HBV col­lab axed af­ter clin­i­cal hold, but biotech be­lieves safe­ty in­ci­dent is not treat­ment-re­lat­ed

The FDA has placed a clinical hold on a Phase IIa study of Antios Therapeutics’ investigational hepatitis B med, CEO Greg Mayes confirmed to Endpoints News in an emailed statement.

A safety report was delivered to the biotech on May 17 after a patient dosed in a triple combination cohort of the study had experienced bradycardia and hypotension. The triple combo included Antios’ ATI-2173, Assembly Biosciences’ vebicorvir and Viread, an approved antiviral for HIV and hepatitis B.

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Tim Schoen, BioMed Realty CEO

Life sci­ences de­vel­op­er Bio­Med Re­al­ty buys San Fran­cis­co ho­tel for $75M — re­port

In a somewhat unconventional deal, life sciences real estate developer BioMed Realty has bought a 169-room Hilton Garden Inn in South San Francisco for $75 million, the San Francisco Business Times reported.

BioMed Realty, an affiliate of Blackstone, has multiple life sciences and technology office projects in the Bay Area, including three sites within a five-minute drive of the hotel.

While the sale of the hotel property was announced earlier this month, the sellers, Summit and GIC, did not identify the buyer at the time.

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Pfizer CEO Albert Bourla at the World Economic Forum (Gian Ehrenzeller/Keystone via AP Images)

All about ac­cess: Pfiz­er moves to a non-prof­it mod­el for drug sales in 45 low­er-in­come coun­tries

Leading the way to increase access to cheaper drugs worldwide, Pfizer said Wednesday it will provide all current and future patent-protected medicines and vaccines available in the US or EU on a not-for-profit basis to about 1.2 billion people in 45 lower-income countries.

Rwanda, Ghana, Malawi, Senegal and Uganda are the first five countries to sign on to this accord, which will also seek to blaze new paths for quick and efficient regulatory and procurement processes to reduce the usual delays in making new medicines and vaccines available in these countries.