Image credit: Shutterstock

Re­searchers in biotech, acad­e­mia and Big Phar­ma are of­fer­ing puz­zle pieces to crack CAR-T for sol­id tu­mors. Will they ever snap to­geth­er?

The idea seemed promising enough.

By the time a group of scientists reported an attempt to treat colon cancer with engineered T cells drawn from patients, expanded and armed with artificial surface proteins in 2010, the experimental therapy — known as CAR-T, short for chimeric antigen receptor transduced T cells — had turned from an eccentric therapeutic proposal to a somewhat viable approach being tested in the clinic. The target, HER2, was one of the most extensively studied targets in cancer, implicated in cancers of breast, bladder, ovary, pancreas, and more. A “next-generation” construct containing a fragment of a well-known antibody, deployed alongside additional tried and true tweaks, looked like a promising next step.

That’s not to mention the study was being conducted by Steve Rosenberg’s lab — the famed National Cancer Institute group that had produced some of the earliest data that convinced scientists of T cells’ ability to attack solid tumors.

Yet the trial took a shocking and tragic turn. Within 15 minutes of receiving the infusion, the first patient had serious trouble breathing. She was sent to the hospital, intubated, and died five days later.

“I think it shut every CAR-T cell therapy study down which targeted HER2 at the time,” recalled Stephen Gottschalk, who was working on a different HER2 program himself at Baylor College of Medicine. “We spent quite a lot of time with the FDA coming up with an approach that would allow us to do it safely.”

While CAR-Ts for hematological malignancies have largely sailed through those early safety scares — a group at Memorial Sloan Kettering had disclosed another death in a hematology trial that same year — and impressed the biopharma world with astonishing response rates, the same can’t be said about solid tumor efforts. Early clinical trials that didn’t turn up serious side effects also failed to demonstrate nearly the same level of efficacy seen in acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Rather than giving up, both academic and industry researchers are doubling down, thanks in part to the big success in the hematologic space and the large market that awaits anyone who can finally unlock any kind of solid tumors with CAR-T.

The few skeptics haven’t stopped a torrent of venture dollars from propelling these efforts, most still preclinical, that promise to tear down the well-documented roadblocks now shielding many cancers from these potent killing cells. The question boils down to how you choose among them — and who will be the last ones standing.

Defining the challenge

Martin Pule remembers the early days when everything was harder in CAR-T.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Alaa Halawa, executive director at Mubadala’s US venture group

The ven­ture crew at Mubadala are up­ping their biotech cre­ation game, tak­ing care­ful aim at a new fron­tier in drug de­vel­op­ment

It started with a cup of coffee and a slow burning desire to go early and long in the biotech creation business.

Wrapping up a 15-year discovery stint at Genentech back in the summer of 2021, Rami Hannoush was treated to a caffeine-fueled review of the latest work UCSF’s Jim Wells had been doing on protein degradation — one of the hottest fields in drug development.

“Jim and I have known each other for the past 15 years through Genentech collaborations. We met over coffee, and he was telling me about this concept of the company that he was thinking of,” says Hannoush. “And I got immediately intrigued by it because I knew that this could open up a big space in terms of adding a new modality in drug discovery that is desperately needed in pharma.”

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,500+ biopharma pros reading Endpoints daily — and it's free.

Chat­G­PT with phar­ma da­ta de­buts for med­ical meet­ings, be­gin­ning with AACR

What do you get when you combine ChatGPT generative AI technology with specific pharma and clinical datasets? A time-saving tool that can answer questions about medical conference abstracts and clinical findings in seconds in one new application from ZoomRx called FermaGPT.

ZoomRx is debuting a public version of its generative AI product specifically for medical conferences beginning this week for the upcoming American Association for Cancer Research (AACR) annual meeting that runs April 14-19.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,500+ biopharma pros reading Endpoints daily — and it's free.

FDA+ roundup: Leg­isla­tive asks for 2024 fo­cus on more au­thor­i­ties, gener­ic drug com­pe­ti­tion

The FDA’s legislative priorities for the next year highlight the agency’s focus on expanding generic drug competition, backstopping the supply chain and growing its current authorities.

On the new authorities front, FDA is seeking to expand its mandatory recall authority for all drugs, as the agency has been embroiled in a long process to remove some from the market. Covis Pharma refused to pull its preterm birth drug Makena, which won accelerated approval, for almost five years after failing its confirmatory trial. The company has since reversed course after a negative adcomm.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Sanofi, Re­gen­eron boast PhI­II win with Dupix­ent in COPD, clear­ing first bar for ex­pan­sion

Dupixent, the blockbuster anti-inflammatory drug from Sanofi and Regeneron, has cleared a high-stakes Phase III study in chronic obstructive pulmonary disease, the companies announced Thursday morning.

If they hold up in a second, identical trial, the data pave the way for Dupixent to become the first biologic to treat patients whose COPD remains uncontrolled despite being on maximal standard-of-care inhaled therapy — the patient population studied in the pivotal program. The companies had spotlighted this as a key readout as they look to expand the Dupixent franchise and explore its full potential.

Genen­tech to stop com­mer­cial man­u­fac­tur­ing at Cal­i­for­nia head­quar­ters

Genentech is halting commercial manufacturing at its California headquarters — and laying off several hundred employees.

The move is the result of a decision Genentech made in 2007 to relocate manufacturing operations from its South San Francisco headquarters location to other facilities or move the work to CDMOs, said Andi Goddard, Genentech’s SVP of quality and compliance for pharmaceutical technical operations, in an interview with Endpoints News. Genentech has made changes in capabilities and invested more in technology, so it doesn’t need as many large-scale manufacturing facilities as it did in the past, she said.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,500+ biopharma pros reading Endpoints daily — and it's free.

In­cyte wins ac­cel­er­at­ed ap­proval for PD-1 in rare skin can­cer

Incyte touted an accelerated approval for its PD-1 retifanlimab in a rare skin cancer on Wednesday, roughly a year and a half after the drug suffered a rejection in squamous cell carcinoma of the anal canal (SCAC).

Retifanlimab, marketed as Zynyz, was approved for metastatic or recurrent locally advanced Merkel cell carcinoma (MCC), a fast-growing skin cancer typically characterized by a single, painless nodule. It’s roughly 40 times rarer than melanoma, according to the nonprofit Skin Cancer Foundation — but incidence is growing, particularly among older adults, Incyte said in its announcement.

A new study finds that many patient influencers are sharing prescription drug experiences along with health information.

So­cial me­dia pa­tient in­flu­encers ‘danc­ing in the gray’ of phar­ma mar­ket­ing, more clar­i­ty need­ed, re­searcher says

It’s no surprise that patient influencers are talking about their health conditions on social media. However, what’s less clear is what role pharma companies are playing, how big the patient influencer industry is, and just how is information about prescription drugs from influencers relayed — and received — on social media.

While University of Colorado associate professor Erin Willis can’t answer all those questions, she’s been researching the issue for several years and recently published new research digging into the communication styles, strategies and thinking of patient influencers, many of whom partner with pharma companies.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 163,500+ biopharma pros reading Endpoints daily — and it's free.