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The U.S. Food and Drug Administration is expected to approve exa-cel gene-editing treatment for sickle cell disease.
Exa-cel would be the first approved medicine in the U.S. to use CRISPR gene-editing technology.
Vertex Pharmaceuticals and CRISPR Therapeutics co-developed the treatment, which could cost around $2 million per patient.

At age 19, Joe Tsogbe underwent his first hip replacement. In his 20s, he averaged about nine hospitalizations a year. By his 30s, that rose to more than a dozen. 
All the result of sickle cell disease, an inherited blood disorder where a genetic mutation causes normally full-moon shaped red blood cells to form into half moons and get stuck inside blood vessels, restricting blood flow and causing bouts of excruciating pain. 

The disease affects about 100,000 people in the U.S., many of whom are Black. Few treatments are available, and the only cure is a bone marrow transplant where a patient receives healthy blood stem cells from a donor. New genetic treatments aim to offer relief while eliminating the need to track down donors.
Tsogbe, now 37, received one of those options, known as exa-cel and co-developed by Vertex Pharmaceuticals and CRISPR Therapeutics, via a clinical trial in 2021. The treatment uses Nobel Prize-winning technology called CRISPR to edit a person’s DNA and alleviate the symptoms of sickle cell disease. 
U.S. regulators are expected to approve exa-cel for use in sickle cell patients by the end of this week. The U.K. approved it under the brand name Casgevy last month.
Regulators in the U.S. are also reviewing another gene therapy from Bluebird Bio called lovo-cel. It works differently than exa-cel but is administered similarly and is also intended to eliminate pain crises. It’s expected to be approved later this month.
Approval of exa-cel by the U.S. Food and Drug Administration would mark a scientific milestone about a decade after the discovery of CRISPR and a breakthrough for patients desperate for a better option.

It could also present a major test for the American health-care system, with Wall Street eyeing a price tag of around $2 million per patient. Tens of thousands of people could be eligible. 

First-of-its-kind treatment

In 2012, researchers Jennifer Doudna and Emmanuelle Charpentier published their seminal paper on a system for editing genes called CRISPR-Cas9. The finding sparked a rush of companies seeking to leverage that insight to treat various diseases.
Sickle cell emerged as a prime target.
Scientist Linus Pauling described sickle cell as the first molecular disease in 1949. The disorder is most common in Africa, where the sickle cell gene helped protect against malaria. People with one copy of the mutation usually don’t have any symptoms of the disease, while people with two copies – one from each parent – can develop severe complications.
One edit to a patient’s genes via CRISPR technology could turn on what’s called fetal hemoglobin, a protein that normally shuts off shortly after birth, to help red blood cells keep their healthy shape. And the work could be done in a lab: Blood stem cells are extracted, edited and then infused back into the patient’s blood stream.
“We are more or less training the cells to express and to produce more of this fetal hemoglobin,” said Dr. Markus Mapara, director of blood and marrow transplantation at NewYork-Presbyterian/Columbia University Irving Medical Center, who treated patients in the exa-cel trials.
While the treatment itself is administered just once, the whole process takes months.
Blood stem cells are extracted and isolated before being sent to Vertex’s lab, where they’re genetically modified. Once ready, patients receive chemotherapy for a few days to clear out the old cells and make room for the new ones. After the new cells are infused, recipients spend weeks in the hospital recovering. 

A researcher watches the CRISPR/Cas9 process through a stereomicroscope at the Max-Delbrueck-Centre for Molecular Medicine.
picture alliance | picture alliance | Getty Images

Vertex and CRISPR made a pact in 2015 to co-develop gene-editing treatments for genetic diseases, including sickle cell. As part of the deal, Vertex will take the lead on launching exa-cel, pending approval. 
Vertex sees exa-cel as a multibillion-dollar opportunity. The company plans to focus on the roughly 32,000 people in the U.S. and Europe with the most severe forms of the disease, like Tsogbe. 
Vertex is also seeking approval to use exa-cel for treat another blood disorder called beta thalassemia. That FDA decision is slated for March.
Yet Wall Street is skeptical exa-cel will be big business. Analysts see $1.2 billion in exa-cel sales for Vertex in 2028, a sliver of the $14 billion in revenue they’re projecting for the whole company that year, according to FactSet. 

The cost of a possible cure

While Mapara said it’s too soon to call exa-cel a cure, he shows prospective patients charts from clinical trials displaying how many pain crises people experienced before and after the treatment. For most participants, the new number is zero.
“It’s mind-blowing,” said Mapara, who is a paid consultant for Vertex and CRISPR. “You really see how effective this treatment has really been.”

More CNBC health coverage

But the lengthy timeline for the treatment, along with the risk of chemotherapy-induced infertility, could make exa-cel a difficult option for some patients. Plus, it would only be available at a limited number of specialized health-care facilities, which could further curb availability. And then there’s the cost.
Wall Street expects Vertex to charge about $2 million per patient for the treatment. That wouldn’t make exa-cel the most expensive gene therapy, with recently approved treatments exceeding $3 million per person. But it could be made available to tens of thousands more patients than other gene therapies, a factor that could make insurers more reluctant to widely cover it.
For Tsogbe, any price is worth it.

Joe Tsogbe with his mother. Tsogbe received exa-cel, a gene-editing treatment for sickle cell disease, in 2021.
Credit: Joe Tsogbe

As a baby in the West African country of Togo, Tsogbe cried while his fingers, toes, knees and other joints swelled. His mother took him to multiple doctors until a specialist diagnosed Tsogbe with sickle cell disease. At the time, there weren’t many available treatments.
But Tsogbe promised his mother that he would travel to the United States and find a cure for sickle cell so he wouldn’t be sick anymore. He moved to the U.S. at age 16 and eventually found the exa-cel trial.
He hasn’t experienced a pain crisis since receiving the treatment about two years ago. It hasn’t erased the damage his body had already accumulated, nor has it completely eliminated the aches and pains. But it’s kept him out of the hospital, and he’s busier than ever. He runs two entertainment companies and teaches dance, activities he’s always loved but that previously left him drained. 
Last year, he went back to Togo to visit his mother for the first time since he left in 2003 as, in his words, a totally different person.
“In a way I kept my promise,” Tsogbe said. 
— CNBC’s Patrick Manning contributed to this report. More

The last weeks of the 2023 box office will be dominated by Warner Bros. Discovery releases.
The studio is capping off the year with three blockbuster features — “Wonka,” “Aquaman and the Lost Kingdom” and “The Color Purple.”
Box-office analysts are also keeping a keen eye on Universal’s new animated film “Migration.”

Timothee Chalamet stars as a young Willy Wonka in Warner Bros.’ “Wonka.”
Warner Bros. Discovery

LOS ANGELES — There are just a few weeks left at the 2023 box office, and they’ll be dominated by movies from Warner Bros.
The studio is capping off the year with three big features — “Wonka,” “Aquaman and the Lost Kingdom” and “The Color Purple” — although it’s unclear whether any or all of them will be hits.

December is a crucial time for the domestic box office. In the five years before the pandemic, the month accounted for more than $1 billion in ticket sales, according to data from Comscore. While December 2021 nearly hit this mark, aided by the release of “Spider-Man: No Way Home” from Sony and Disney, December 2022 tallied less than $700 million.
Overall, the 2023 box office lags around 19% compared with 2019, standing at $8.3 billion as of Dec. 3. Box-office analysts are hopeful that it could reach $9 billion before the end of the year.
After all, with the weekend release of Beyonce’s “Renaissance” tour film as well as continued ticket sales from Lionsgate’s “Hunger Games: The Ballad of Songbirds and Snakes,” Universal’s “Trolls Band Together” and Disney’s “Wish,” the domestic box office generated nearly $100 million in the first three days of December, according to Comscore data.

Remaining December releases

Dec. 8 — “The Boy and the Heron” (GKIDS)
Dec. 15 — “Wonka” (Warner Bros. Discovery)
Dec. 22 — “Aquaman and the Lost Kingdom” (Warner Bros. Discovery)
Dec. 22 — “Migration” (Universal)
Dec. 22 — “Anyone But You” (Sony)
Dec. 22 — “The Iron Claw” (A24)
Dec. 22 — “American Fiction” (Amazon-MGM)
Dec. 25 — “The Color Purple” (Warner Bros. Discovery)
Dec. 25 — “Ferrari” (Neon)
Dec. 25 — “The Boys in the Boat” (Amazon-MGM)

“Like so many sporting events, contests of skill or the proverbial horse race, the outcome of any given box office year often comes down to the final moments,” said Paul Dergarabedian, senior media analyst at Comscore. “This year, December is particularly important in terms of the high-profile lineup of films on the calendar on which the full weight of a less than stellar month of November and a rather slow Thanksgiving [rests].”
Warner Bros. releases will have a lot to say about whether December will ring up big bucks. The studio has already provided the 2023 box office with the billion-dollar global hit “Barbie,” and its three December releases are expected to offer the biggest box-office punch alongside Universal and Illumination’s animated feature “Migration.”

Warner Bros. Discovery is still evolving after WarnerMedia and Discovery merged only last year. Chief Executive David Zaslav has been working to pay down debt while building up free cash flow in order to set up potential acquisitions of smaller studios. Part of that cost-cutting started early in the new company’s history with the axing of “Batgirl” and “Scoob! Holiday Haunt” before their releases and the cancellation of more than a dozen TV shows set for its streaming service.
Shares of the company are up 15% year to date through Wednesday.

Taraji P. Henson stars in Warner Bros. “The Color Purple.”
Warner Bros. Discovery

Both “Wonka” and “Aquaman and the Lost Kingdom” are expected to generate between $32 million and $42 million during their openings, according to BoxOffice.com. “The Color Purple” is set for at least a $13 million debut. (“Migration” is forecast to tally between $20 million and $30 million.)
Expectations are high that “Wonka” will deliver families to theaters, as the musical prequel has already generated goodwill with critics, scoring a clear “Fresh” rating on Rotten Tomatoes. And “The Color Purple,” also a musical, could lure in a more mature crowd, given the movie’s literary and theatrical pedigree.

The king of Atlantis vs. a family of ducks

It’s Warner Bros.’ “Aquaman” sequel that is most worrisome to box-office analysts. Audiences have been lackluster on superhero flicks this year, with Disney’s Marvel Cinematic Universe posting its worst-ever opening weekend in its history with “The Marvels.” The film has generated less than $200 million globally since its Nov. 10 release through the weekend, another low point for the MCU.
DC has faced deeper difficulties at the box office compared with rival Marvel. “Shazam: Fury of the Gods” and “Blue Beetle” both tallied less than $150 million during their global run in theaters this year, and “The Flash” secured less than $275 million worldwide.
“The DC brand, in particular, is very challenged after three middling-to-soft performances already this year and a general aura of limbo among fans knowing that the franchise is effectively getting a soft reboot in 2025,” said Shawn Robbins, chief analyst at BoxOffice.com. “I’m very cautious on ‘Aquaman’ projections under those circumstances.”
The new “Aquaman” film has a lot to live up to, as well. The first film, released back in 2018, generated more than $1 billion at the global box office, making it the highest-grossing film in the DC Extended Universe franchise. Much of the interest from fans came following the 2017 release of “Justice League,” as moviegoers expected “Aquaman” to launch the franchise forward.

Jason Momoa stars as Arthur Curry, aka Aquaman, in Warner Bros.’ “Aquaman and the Lost Kingdom.”
Warner Bros. Discovery

The majority of its ticket sales were international, including nearly $300 million from the China region alone. Domestic ticket sales were just 30%, or $335 million, of the movie’s total global box office, according to Comscore.
The new “Aquaman” will also be released in China. But non-Chinese movies have not seen the same benefit in China as in the pre-pandemic years.
While Disney and 20th Century’s “Avatar: The Way of Water” secured $245 million in China, American superhero flicks have failed to drum up interest in the country in the last year. Marvel’s “Ant-Man and the Wasp: Quantumania” generated only $40 million in ticket sales, DC’s “The Flash” took in just $25 million from the region, and the MCU’s “Black Panther: Wakanda Forever” grabbed just $15 million. “Guardians of the Galaxy: Vol. 3” grossed $86 million in China.
“Aquaman and the Lost Kingdom” also faces an uphill battle because of comments from the new co-head of DC Studios, James Gunn. He effectively said the remaining films in the DCEU, including the “Aquaman” sequel, will have no connection to future projects from the studio. Thus, fans have one less reason to head out to cinemas.
The other wild card is Universal’s “Migration,” a comedy about a family of ducks that opens the same day as the new “Aquaman.”
The Comcast-owned studio has flourished at the box office in recent years with its animated fare from its Illumination and DreamWorks animation arms. “Minions: The Rise of Gru,” “The Super Mario Bros. Movie” and “Trolls Band Together” have delivered strong ticket sales in the wake of the pandemic. Of course, all those films are tied to existing intellectual property.
“Migration” is an original story, but if it’s well-received it could spark its own franchise for the studio.
“No original animated movie has reached the kind of mega-blockbuster numbers of ‘Mario’ or ‘Minions’ during the post-pandemic era yet,” Robbins noted. “That fact alone makes it difficult to project what kind of ceiling ‘Migration’ may or may not have in the wake of films like Disney’s ‘Wish’ and Pixar’s ‘Elemental’ this year.”
Yet few would count out Universal to be the studio to achieve such a feat, especially since the movie will open as kids begin their holiday school breaks.
“As the only major animated film opening in theaters later this month, though, there is certainly a path to success,” Robbins added. “If any studio can break the trend and capture wide family audience appeal with an original animated flick right now, it’s Illumination.”
Disclosure: Comcast is the parent company of NBCUniversal and CNBC. NBCUniversal is the distributor of “Migration,” “Minions: The Rise of Gru,” “Trolls Band Together” and “The Super Mario Bros. Movie.” NBCUniversal also owns Rotten Tomatoes. More

McDonald’s plans to open 10 locations of CosMc’s, a new spinoff brand, to test whether the concept could work across the U.S. and other markets.
The burger chain is positioning CosMc’s as a fast, convenient way to grab a pick-me-up snack or coffee.
The name for the new brand comes from CosMc, a McDonaldland mascot that appeared in advertisements in the late 1980s and early 1990s.

McDonald’s CosMc’s Restaurant.
Courtesy: McDonald’s

McDonald’s will open the first location of its new spinoff brand CosMc’s this week in Bolingbrook, Illinois.
The fast-food giant plans to open 10 CosMc’s locations, including nine restaurants in Texas, by the end of 2024 in a test. McDonald’s will then spend a year analyzing data to decide whether it will expand the small-format chain.

The name for the new brand comes from CosMc, a McDonaldland mascot that appeared in advertisements in the late 1980s and early 1990s. CosMc is an alien from outer space who craves McDonald’s food. The company has leaned more into marketing its mascots after seeing success with the Grimace Birthday Meal earlier this year.
The burger chain first revealed it was creating CosMc’s as a spinoff in July, but withheld more details about its plans. Photos of the Bolingbrook location surfaced on X, formerly known as Twitter, earlier this week.
With a menu that includes old favorites such as Egg McMuffins and M&M McFlurries, and new items such as Churro Frappes and pretzel bites, McDonald’s is positioning CosMc’s as a fast, convenient way to grab a pick-me-up snack or coffee.
“When 3 p.m. hits, and you need a boost, take a trip to CosMc’s,” a narrator said in a video shown to investors Wednesday.

1980s McDonald’s Commercial screenshot featuring CosMc.
Source: McDonald’s | YouTube

McDonald’s specifically set out to create a brand that could sell customizable drinks and coffee popular in the afternoon segment.

“This is a $100 billion category growing faster than the rest of the [informal eating-out segment] and with superior margins,” McDonald’s CEO Chris Kempczinski told investors.
CosMc’s restaurants will have a smaller real-estate footprint than a typical McDonald’s location, but the new locations are testing a range of layouts, including multiple drive-thru lanes. Customers using credit cards will also be able to pay at the drive-thru speaker, speeding up service times.
The announcement was part of the company’s investor day. Executives unveiled long-term targets for its new restaurant development, plans to recruit 100 million new loyalty program members and a strategic partnership with Google.
But Kempczinski emphasized that investors shouldn’t get too excited yet about CosMc’s.
“Let me emphasize again, we’re talking about 10 stores,” he told investors on Wednesday. “The big story isn’t about CosMc’s, per se. The big story is what it says about McDonald’s and our potential. To think, a little over a year ago, this was an idea, and this week we’re opening the first test site.”
But if the test works out, CosMc’s could open across the globe.
“It’s not worth our time to develop an idea that will only work in one market,” Kempczinski said when explaining why McDonald’s created the brand.
Still, McDonald’s past efforts to expand beyond its primary business haven’t been successful. In the late 1990s, it bought Donatos Pizza and Boston Market, and a stake in a fledgling Chipotle Mexican Grill. Less than a decade later, it had divested from all three, which had become distractions as McDonald’s struggled.  More

AbbVie said it will acquire neuroscience drugmaker Cerevel Therapeutics for roughly $8.7 billion. 
AbbVie will pay $45 per share for Cerevel and expects to complete the acquisition in the middle of 2024. 
The deal is AbbVie’s latest attempt to expand its drug pipeline as its top-selling treatments, such as Humira, face generic competition.

A sign stands outside a Abbvie facility in Cambridge, Massachusetts, May 20, 2021.
Brian Snyder | Reuters

AbbVie on Wednesday said it will acquire neuroscience drugmaker Cerevel Therapeutics for roughly $8.7 billion. 
Under the terms of the deal, AbbVie will pay $45 per share for Cerevel. AbbVie said it expects to complete the acquisition in the middle of 2024. 

Shares of Cerevel jumped 16% after the close Wednesday to nearly $43 per share, just below the purchase price. Shares of Abbvie were down less than 1% in extended trading.
The deal is AbbVie’s latest attempt to expand its drug pipeline as its top-selling treatments, such as Humira, face generic competition. Just last week, AbbVie agreed to buy cancer drug developer Immunogen for nearly $10 billion. 
Cerevel will specifically beef up AbbVie’s portfolio for psychiatric and neurological disorders “where significant unmet needs remain,” according to a release from AbbVie. 
Cerevel will bring over drugs such as Emraclidine, an experimental treatment for both schizophrenia and Alzheimer’s disease psychosis, including symptoms like hallucinations and delusion. That drug is currently in a phase one study in elderly volunteers. 
“Our existing neuroscience portfolio and our combined pipeline with Cerevel represents a significant growth opportunity well into the next decade,” said Richard Gonzalez, CEO and chairman of AbbVie, in a statement. “AbbVie will leverage its deep commercial capabilities, international infrastructure, and regulatory and clinical expertise to deliver substantial shareholder value with multibillion-dollar sales potential across Cerevel’s portfolio of assets.”
AbbVie said it will hold an investor conference call about the deal on Thursday at 8:00 a.m. ET. More