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US court rules in favor of AbbVie’s Humira patents; Merck’s Keytruda fails in two late-stage cancer trials
This week, Phispers is packed with news on oncology drugs failing key trials. Last month, Merck’s blockbuster cancer therapy Keytruda had failed to meet its main goal in a phase 3 study in patients with head and neck cancer. This week, the drug failed in two more indications — as a first-line therapy in combination with Eisai’s Lenvima for liver cancer and as a later-line treatment for metastatic prostate cancer.
Similarly, AstraZeneca has discontinued a phase 3 trial testing its next-generation checkpoint inhibitor monalizumab with Eli Lilly’s Erbitux (cetuximab) in a type of head and neck cancer after the combo failed to show positive results. The pharma has also removed a Moderna-partnered cardiovascular disease candidate, AZD8601, and a Wee1 inhibitor, adavosertib, for ovarian cancer, solid tumors and uterine serous cancer, from its phase 2 pipeline.
Another late-stage trial evaluating a combination of two Bristol Myers Squibb drugs – Opdivo and Yervoy – failed to meet the primary goal to treat localized kidney cancer. Just last week, Roche’s cancer drug Tecentriq had failed a phase 3 study in post-surgery kidney cancer.
In positive news, the FDA has lifted a hold on a phase 1b study of Celyad Oncology’s CAR-T cell therapy. The agency had put a hold on the study after the death of two trial patients. And Novo Nordisk has announced positive top-line data from two phase 3 trials evaluating its once-weekly insulin – icodec – in adults with type 2 diabetes. Similarly, the FDA has approved Coherus BioSciences’ Cimerli as the first interchangeable biosimilar of Roche’s blockbuster eye drug Lucentis (ranibizumab), which raked in US$ 1.4 billion last year. Cimerli has been approved to treat five retinal indications.
In legal news, a US appeals court has ruled in favor of AbbVie, ascertaining that the drugmaker did nothing unlawful by building up a patent thicket around its blockbuster drug Humira. And in regulatory news, the FDA has issued a Form 483 with three observations to Aurobindo Pharma’s manufacturing facility at Pydibhimavaram in the state of Andhra Pradesh, India.
In M&A news, AbbVie has entered into a new drug discovery partnership with neurological diseases expert Sosei Heptares for three neurological therapies. Sosei is entitled to an US$ 40 million upfront payment along with US$ 1.2 billion in milestone payments. And French pharma Ipsen has signed a potential US$ 1.6 billion partnership with US biotech Marengo Therapeutics for two experimental T cell receptor therapies.
US appeals court rules in favor of AbbVie’s Humira patent thicket
A US appeals court has ruled that pharma giant AbbVie did nothing unlawful by building up a patent thicket around its mega blockbuster drug Humira to block competition.
AbbVie’s 132 additional patents for Humira do not violate antitrust law, the US circuit judge ruled. The judge also rejected claims that the patents allegedly kept generic competition out of the market even after the original patent on Humira had expired.
The ruling came in response to a lawsuit filed by a group of welfare-benefit plans that pay for Humira. The group had sued AbbVie in 2019, alleging that Humira’s patents created an illegal monopoly and scared off competitors. This led to higher prices for the drug, they had alleged. The lawsuit had also alleged that AbbVie violated the antitrust law by entering into agreements to settle patent lawsuits with competitors in exchange for not introducing Humira biosimilars in the US until 2023. A federal judge had dismissed the case against AbbVie in 2020. Now, the circuit judge has upheld the decision.
Humira, which is used to treat rheumatoid arthritis, Crohn’s disease, ulcerative colitis and psoriasis, raked in over US$ 21 billion in 2021 global sales. The patent that covered Humira had expired in 2016, but the last of its 132 patents will expire in 2034. Next year, Humira will face competition from nine biosimilars.
AbbVie-Sosei to sign a US$ 1.2 billion neuro disease drug pact: AbbVie has entered into a new drug discovery partnership with neurological diseases expert Sosei Heptares for the discovery, development and marketing of therapies for neurological ailments. Under the deal, Sosei will perform and fund R&D activities of the neurological targets. AbbVie has the option to license up to three programs and oversee their clinical, regulatory and commercial development.
Sosei will receive an upfront payment of US$ 40 million on signing the deal, and another US$ 40 million in near-term research milestone payments over three years. Sosei is entitled to get up to US$ 1.2 billion in milestone payments. The new agreement builds on an earlier inflammatory and autoimmune diseases discovery deal signed by the two companies in 2020.
Merck’s blockbuster drug Keytruda fails in two late-stage cancer trials
Last month, Merck’s blockbuster cancer therapy Keytruda had failed to meet its main goal in a phase 3 study in patients with head and neck cancer. This week, the drug failed in two more indications — as a first-line therapy in combination with Eisai’s Lenvima for liver cancer and as a later-line treatment for metastatic prostate cancer.
In the first case, the combination of Keytruda and Eisai’s Lenvima was compared to Lenvima alone in liver cancer that cannot be removed by surgery. In a phase 3 study, the combo therapy failed to significantly extend patients’ lives and stall tumor progression or death when compared with Lenvima alone.
In the second failure, Keytruda plus chemotherapy failed as a treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), which does not respond to hormone therapy. The combo failed to best chemotherapy alone in overall and progression-free survival in over 1,000 trial patients.
This is Keytruda’s second flop in mCRPC in recent months. In March, Keytruda and AstraZeneca-partnered Lynparza had failed to outperform Johnson & Johnson’s Zytiga or Astellas and Pfizer’s Xtandi in mCRPC patients who had previously got one of the anti-androgen therapies.
After Roche, BMS’ drug combo fails in late-stage post-surgery kidney cancer study
Only a few days back, Roche’s cancer drug Tecentriq had failed a phase 3 study in post-surgery kidney cancer. And now, a late-stage trial evaluating a combination of Bristol Myers Squibb’s drugs – Opdivo and Yervoy – failed to meet the primary goal to treat localized kidney cancer.
The drug combo failed to meet the key endpoint of disease-free survival when used as an adjuvant treatment after surgery in patients with localized renal cell carcinoma. The combo failed to top placebo at preventing disease recurrence or death in moderate- or high-risk relapse patients, an independent data review panel found.
All hope, however, is not lost for BMS yet. The results for the trial evaluating Opdivo alone in adjuvant kidney cancer is yet to come out. The Opdivo-Yervoy drug combo is already approved in the US as a first line of treatment for patients with renal cell carcinoma.
Aurobindo Pharma’s Indian API manufacturing facility hit by FDA’s Form 483
The US Food and Drug Administration (FDA) has issued a Form 483 with three observations to Aurobindo Pharma’s manufacturing facility at Pydibhimavaram in Andhra Pradesh, India.
Back in May 2019, FDA had classified the Pydibhimavaram facility – a non-antibiotic active pharmaceutical ingredients manufacturing facility – as OAI (official action indicated). In June 2019, the facility had received a warning letter. The Indian pharma had responded to the warning letter and addressed the issues. The FDA authorities inspected the facility again between July 25 and August 2 this year.
The pharma said it will respond to the FDA within the stipulated timeline and work closely with the agency to address the observations at the earliest.
Coherus’ Cimerli becomes first interchangeable biosimilar of Roche’s Lucentis
The FDA has approved Coherus BioSciences’ Cimerli as the first interchangeable biosimilar of Roche’s blockbuster eye drug Lucentis (ranibizumab), which raked in US$ 1.4 billion last year. Cimerli has been approved to treat five retinal indications.
Cimerli is expected to be available in the market in October. Earlier this year, Samsung Bioepis and Biogen’s Byooviz received approval as the first Lucentis biosimilar in the US, but failed to win the interchangeable status.
AstraZeneca discontinues phase 3 trial of monalizumab in head and neck cancer
AstraZeneca has discontinued a phase 3 trial testing its next-generation checkpoint inhibitor monalizumab with Eli Lilly’s Erbitux (cetuximab) in a type of head and neck cancer after the combo failed to show positive outcome.
The study was evaluating the combo against Erbitux in patients with recurrent or metastatic squamous cell carcinoma of the head and neck who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors. Astra decided to discontinue the trial after the combo failed to meet a pre-defined threshold for efficacy in an interim analysis.
The partners are conducting multiple trials testing monalizumab in combination with Imfinzi in lung cancer. AstraZeneca had licensed the rights to anti-NKG2A antibody monalizumab from France’s Innate Pharma in 2018 for an upfront payment of US$ 250 million plus milestone payments.
AstraZeneca has also removed a Moderna-partnered cardiovascular disease candidate – AZD8601 – undergoing phase 2 trials, from its pipeline. AZD8601 is a therapy based on messenger RNA encoding vascular endothelial growth factor (VEGF-A).
The drugmaker has also removed Wee1 inhibitor adavosertib that was in phase 2 for ovarian cancer, solid tumors and uterine serous cancer. It was being studied with an Imfinzi combination.
Regeneron terminates four studies of its Covid-19 antibody combo: Regeneron has terminated four studies of REGEN-COV, its monoclonal antibody combination. The FDA halted the use of the drug in January citing data that suggested the combo – casirivimab and imdevimab – was ineffective against the Omicron variant of the coronavirus. All studies, from phase 1 to phase 3, cited "emerging SARS-CoV-2 variants impacting susceptibility to study drug” as the reason for the termination.
Novo Nordisk’s once-weekly insulin drug hits primary goals in two phase 3 trials
Novo Nordisk has announced positive top-line data from two phase 3 trials evaluating its once-weekly insulin – icodec – in adults with type 2 diabetes.
In one trial, hemoglobin A1c, a measure of blood sugar, had fallen 1.57 percent from a baseline of 8.5 percent after 26 weeks of treatment. In the other, hemoglobin A1c had fallen 1.16 percent from a baseline of 8.3 percent in the insulin icodec cohort.
The Danish pharma did not find any statistically significant difference in severe or clinically significant hypoglycemia. The company said the drug appeared safe and well tolerated.
Novo now has data from five of the six phase 3 trials on the drug. The pharma had shared data from three trials earlier this year. All the three studies had hit their primary endpoints. The top-line result from the remaining study is due by the end of the year.
Ipsen signs potential US$ 1.6 billion deal with Marengo for solid tumor therapies
French pharma Ipsen has entered into a potential US$ 1.6 billion partnership with US biotech Marengo Therapeutics for two experimental T cell receptor therapies.
The two candidates, both discovered using Marengo’s proprietary Selective T Cell Activation Repertoire (STAR) antibody fusion platform, are in the early preclinical assessment stage. According to Marengo, the two candidates are being developed for different solid tumor indications. While the biotech will take on preclinical work, Ipsen will run the clinical studies and take care of commercialization.
Ipsen is shelling out US$ 45 million as upfront payment for the two drugs. It has promised another US$ 1.6 billion in milestone payment if both the programs hit all their goals. Marengo will also be eligible to receive tiered royalties.
FDA lifts hold on Celyad’s CAR-T therapy trial: Back in February this year, Belgium-headquartered Celyad Oncology had voluntarily paused a phase 1b study of its CAR-T cell therapy – CYAD-101 – following the death of two trial patients. Soon after that, the FDA had put a hold on the trial.
The agency has now lifted the hold after Celyad made changes to the trial’s eligibility criteria for enrollment to exclude patients with bilateral lung metastases and recent prior history of anti-EGFR antibodies. The biotech plans to resume the trial of the non-gene edited allogeneic CAR-T therapy soon.
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