While other cancer immunotherapies are busy expanding into different tumor types, AstraZeneca’s Imfinzi has been a lung cancer story. But the company is now trumpeting a first-of-its-kind win for the drug.
The addition of Imfinzi to chemotherapy has helped newly diagnosed patients with advanced biliary tract cancer live longer, AZ unveiled Monday. The improvement was statistically significant and clinically meaningful, the company said.
The readout came from an interim analysis of the phase 3 Topaz-1 trial and marked the first time an immuno-oncology regimen beat standard of care in a randomized trial for front-line biliary tract cancer, a rare gastrointestinal cancer that reports about 50,000 new diagnoses each year across the U.S., Europe and Japan.
The trial covered patients with cancers that form in the bile ducts–called cholangiocarcinoma–which is more common in China and Thailand, and with gallbladder cancer, which is mainly found in South America, India and Japan. The umbrellas term also includes ampullary carcinoma, but the trial excluded this disease subtype.
“Patients with advanced biliary tract cancer are in dire need of new treatments as progress in the 1st-line setting has remained largely stagnant for more than 10 years,” said Do-Youn Oh, M.D., Ph.D., from Seoul National University Hospital and principal investigator of the Topaz-1 trial, in a statement.
Last April, the FDA cleared Incyte’s Pemazyre as the first targeted treatment for cholangiocarcinoma. But the drug is meant for patients who have tumors that have an abnormality in the FGFR2 gene and have been previously treated with a standard chemotherapy combo. BridgeBio followed this June with an accelerated approval for Truseltiq in the same setting.
In August, Servier’s Tibsovo branched out into cholangiocarcinoma, but the targeted drug is also limited for previously treated disease bearing an IDH1 mutation.
Although Imfinzi is the first PD-1/L1 inhibitor to succeed in first-line bile duct cancer, it’s not the only one targeting the field. Merck & Co. is running the front-line phase 3 Keynote-966 trial for Keytruda, which started about six months after Imfinzi’s Topaz-1.
Bile duct cancer marks Imfinzi’s second positive gastrointestinal cancer readout in just a few days, Susan Galbraith, AZ’s oncology R&D chief, noted in a statement. The PD-L1 inhibitor’s pairing with AZ’s investigational CTLA-4 inhibitor tremelimumab topped Bayer’s Nexavar as a first-line treatment for liver cancer in the phase 3 Himalaya trial.
Merck’s Keytruda and Bristol Myers Squibb’s Opdivo have previously both posted failures in liver cancer; Opdivo had to remove an accelerated approval in the second line after a confirmatory trial trip-up in the first-line setting. And Keytruda’s conditional nod in the second line is also hanging in the balance.
Besides bile duct cancer and liver cancer, AZ is also evaluating Imfinzi in other GI cancers, including esophageal and stomach cancers. Beyond the immunotherapy, the company has Daiichi Sankyo-partnered Enhertu and Merck-partnered Lynparza under experiments for various GI cancers.
You Say Trintellix, I Say Brintellix: Why a Drug Name in the US Won’t Always Translate Across the Pond Feedzy
As a British citizen living in England but writing on American drug names, I’m in a perfect position to know that many drugs approved in Europe and the U.K. can have very different names from those in the U.S.
Why is that? Well, to find out, Fierce Pharma Marketing sat down with Scott Piergrossi, president of creative at the Brand Institute, a company that has helped name some of the world’s biggest drugs. He’s not explaining the reasoning behind any drug name changes mentioned in this piece, but offering up insight into why different regions may need tweaks–or complete rethinks–in branding for the same drug.
Often, the change in name can be very minor. Let’s take Amgen’s new non-small cell lung cancer drug as an example: In the U.S., the FDA approved the drug as Lumakras, but in in Europe, its counterparts at the European Medicines Agency approved the med as Lumykras earlier this month.
You’ll see this U.S.-Europe divide a lot with drug names–but why? Piergrossi explains that changing a single letter can often provide enough differentiation to satisfy regulatory requirements, which can be different in the U.S. and Europe, “such as changing a vowel to a y, or adding/removing a letter or two.” Just as we see with Lumakras/Lumykras.
Another key reason an agency might reject a name is if they think the name is overly promotional–what the FDA refers to as “misbranding,” such as making misrepresentations about safety or efficacy. Hence, you don’t have antivirals called KillsCOVIDNoSideEffects.
Some examples can seem obvious, but Piergrossi explains there can be more subtle and subjective naming differences that create misleading suggestions in a name.
Take the FDA-approved osteoporosis drug Boniva. In Europe and elsewhere, the drug is sold under the brand name Bonviva. “The latter perhaps suggesting ‘good life’ more so than the former,” Piergrossi says, though he adds that extracting meaning from an invented name, in his experience, is “highly subjective.”
There’s also the rare example of a change mandated after the agency has approved a drug and its name. We saw this with Trintellix, an antidepressant from Takeda and Lundbeck. That’s its newer name: Originally approved as Brintellix, the drug had to change–per the FDA–given that name’s similarity to AstraZeneca’s anti-blood-clotting therapy, Brilinta. Prescribers were actually confusing the two brands, triggering medication errors. Brintellix still bears that name in Europe and elsewhere.
Sometimes, it just comes down to regional preferences at a company. Global pharmas have global teams working on product marketing and name development. “A regional team might prefer one spelling versus another, assuming they are given the latitude to make those decisions, so the name is modified accordingly,” said Piergrossi.
Original Article: fiercepharma.com
GlaxoSmithKline Rushes to Accelerate COVID-19 Antibody Output Amid Omicron-driven Demand Feedzy
GlaxoSmithKline and Vir Biotechnology are rushing to speed up production of their COVID-19 therapy, now that they’re the only companies with an antibody that appears to be truly effective against omicron.
The FDA on Dec. 30 cleared a Samsung Biologics site as a second manufacturing facility to make GSK and Vir’s Xevudy (sotrovimab), a GSK spokesperson told Fierce Pharma.
Along with adding the new facility, GSK and Vir worked with external partners to secure additional batches of drug substance to support supply this year, the spokesperson said via email.
GSK had been planning to commission a new production facility to scale up production and establish a second manufacturing site amid pandemic uncertainty, the spokesperson said. But omicron’s emergence suddenly pushed the acceleration button.
GSK and Vir recently found that sotrovimab retains its strength against omicron in cell cultures, while lab data showed that Eli Lilly’s antibody combo of bamlanivimab and etesevimab and Regeneron’s REGEN-COV cocktail are unlikely to be able to tackle the new variant.
That means, among the three FDA-authorized antibody drugs to treat infected patients, only sotrovimab is still powerful enough to fight omicron. AstraZeneca’s Evusheld is authorized as a prevention method for immuno-compromised people.
After those lab tests, the U.S. government in December temporarily halted distribution of Lilly’s and Regeneron’s offerings. Although the two products are now shipping again, their ability to fight the now-dominant omicron remains questionable.
Demand naturally started to shift to Xevudy. Last week, the Biden administration signed a deal to buy 600,000 additional doses for distribution this quarter.
“We were on the phone with the U.S. government immediately, sharing the data, discussing what was possible from a supply perspective,” said Bart Murray, who leads GSK’s COVID operation in the U.S., as quoted by The Wall Street Journal.
Other countries have also been snagging supplies of Xevudy. A few days ago, Canada signed on for 20,000 doses. GSK also has agreements with Japan, U.K., Singapore, Australia and others. All told,
GSK and Vir have said they expect to manufacture about 2 million doses globally in the first half of 2022.
Before the new deal, GSK had delivered the 440,000 doses it agreed to supply to the U.S. in 2021. The government is still allocating that supply to healthcare facilities. The company now expects to start shipping the 600,000 doses in February and March, the spokesperson said.
Both Regeneron and Eli Lilly have started developing new antibody treatments that could neutralize omicron.
Meanwhile, China’s Brii Biosciences is seeking an FDA green light for its antibody combo of amubarvimab and romlusevimab, which won Chinese approval in December. The company recently said its cocktail also held up against omicron. The U.S. doesn’t yet have any supply agreement with Brii.
Fierce JPM Week: Bristol Myers’ Next-gen Autoimmune Med Not Just Another JAK Drug, Exec Says Feedzy
After a high-profile study turned up safety risks for Pfizer’s JAK inhibitor Xeljanz last year, the FDA put the entire class under a microscope–and it only recently went back to granting new approvals in that class. Bristol Myers Squibb, meanwhile, has a new candidate that the company’s chief medical officer says is safer than the other JAKs.
Speaking during the Fierce JPM Week virtual conference, Bristol’s CMO, Samit Hirawat, said the company’s deucravacitinib is a novel TYK2 inhibitor “with a very specific downstream effect of integrating IL-12, IL-23 and interferon and sparing other cytokines and sparing JAK 1, 2 and 3.”
While Bristol aims to highlight its med’s differences from drugs in the JAK class, TYK2 is known colloquially as JAK4 and is part of the Janus kinase family. That has some industry watchers worried that the FDA may take a tough stance on the candidate amid safety concerns for the larger drug class.
After an FDA submission last year, deucravacitinib is under review to treat moderate to severe plaque psoriasis. The agency’s decision deadline is set for Sept. 10, 2022.
So far in deucravacitinib’s studies, BMS doesn’t “see the hematologic impact that JAK inhibitors do show [and] we don’t see the dysfunction in the liver enzymes that is seen with JAK inhibitors,” Hirawat said during Fierce JPM Week.
Further, “we don’t see dyslipidemia that is shown by JAK inhibitors,” Hirawat added.
Since Xeljanz post-marketing study showed heightened risks of cardiovascular problems and cancer, the FDA has put the entire JAK inhibitor class in a protracted safety review. That process triggered missed approval deadlines for new drug candidates and delayed label expansions for existing meds.
More recently, the FDA started giving new blessings for JAK drugs–but under the condition that they’re used behind old-school TNF inhibitors such as Humira. Pfizer’s new Cibinqo and AbbVie’s Rinvoq recently won eczema approvals, for instance.
As for deucravacitinib, Hirawat said the Poetyk PSO-1 and Poetyk PSO-2 studies–plus trials in Japan and China–show that the med is a “first-in-class” medicine, apparently hoping to differentiate the drug from existing meds at the center of the FDA safety review.
When Bristol bought Celgene for $74 billion back in early 2019, the company had to sell the lucrative psoriasis drug Otezla to score antitrust approval for the deal. The company opted to stick with deucravacitinib, which later beat Otezla in the Poetyk studies by helping more patients achieve 75% skin clearance.
These days, Amgen markets Otezla and is generating blockbuster sales from the psoriasis medicine. For its part, Bristol figures deucravacitinib can generate $4 billion at peak.
And deucravacitinib has some other new indications in the works. BMS is “looking forward to seeing the data imminently” for a phase 2 trial in systemic lupus erythematosus, Hirawat said. If that result is “supportive,” BMS will launch a phase 3 program, he said.
Meanwhile, the drug didn’t meet proof of concept criteria in inflammatory bowel disease last October, but Hirawat said the company is running two studies with higher doses and is “absolutely” committed in that disease. With those results, the company expects to have more information about potential indications to “pursue in the future,” Hirawat said.
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