The drugmaker, which also reported better-than-expected fourth-quarter results on strong Keytruda sales, has already inked multiple deals over the last year, including a $5.5 billion payout to Japan's Daiichi Sankyo for the right to co-develop three antibody drug conjugate cancer drugs."While I feel very good about the progress we've made and the growing portfolio, the diverse and deep portfolio we have in our pipeline, we do continue to believe we need more, and we will continue to prioritize business development," Chief Executive Officer Rob Davis said on a conference call.In addition to deals, Davis said Merck would look for more collaborations similar to the Daiichi Sankyo transactions.Keytruda generated $25 billion in 2023 sales, surpassing peak sales of AbbVie's blockbuster arthritis drug Humira.Keytruda is forecast to top $30 billion in sales by 2026. However, the drug is set to lose its patent protection by the end of the decade.The company's 2023 transactions are already significantly improving Merck's own outlook for future revenue. Merck said it now expects $20 billion from new oncology products in development by the mid-2030s, nearly double its prior oncology pipeline forecast for over $10 billion.It also lifted its mid-2030s outlook for new cardiometabolic products to about $15 billion from more than $10 billion.Merck reported adjusted earnings of 3 cents a share in the fourth quarter, despite taking a charge of $1.69 a share to account for the Daiichi deal. Analysts had expected a loss of 11 cents a share, according to LSEG data.Revenue for the quarter rose 6% to $14.6 billion, compared with estimates of $14.5 billion.Keytruda sales jumped 21% to $6.6 billion as the company was able to increase use of the drug in earlier stage cancers, topping analyst forecast of $6.5 billion.The company forecast 2024 sales between $62.7 billion and $64.2 billion. Analysts, on average, are estimating 2024 sales of $63.5 billion.The New Jersey-based drugmaker expects 2024 earnings of $8.44 to $8.59 per share, above Wall Street estimates of $8.42.Merck also said it has launched a restructuring program to optimize its manufacturing operations related to human and animal health, and expects to complete the program by the end of 2031.Merck expects to record about $4 billion in cumulative pre-tax costs to implement the program. It took a $190 million charge related to the program in the fourth quarter.

Read also: Merck gets USFDA nod for Keytruda plus chemoradiotherapy for FIGO 2014 Stage III-IVA Cervical Cancer

The treatment for different types of blood cancer, known as chimeric antigen receptor T-cell therapies or CAR-T, generally involves extracting disease-fighting white blood cells known as T-cells from a patient, re-engineering them to attack cancer and infusing them back into the body.The European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) said it will review data on secondary malignancies or the development of an additional type of cancer related to the T-cells, after patients use the medicines.The U.S. Food and Drug Administration is also investigating six of these therapies approved in the EU.These include Bristol Myers Squibb's Breyanzi and its partnered therapy, Abecma, with 2seventy bio. J&J unit Janssen and Legend Biotech's Carvykti, Novartis' Kymriah, and Gilead unit Kite's Tecartus and Yescarta are also a part of the review, the EMA said.Read also: AbbVie, Umoja Biopharma collaborate to develop Novel In-Situ CAR-T Cell Therapies

The first agreement provides AbbVie an exclusive option to license Umoja's CD19 directed in-situ generated CAR-T cell therapy candidates. This includes UB-VV111, Umoja's lead clinical program for hematologic malignancies currently at the IND-enabling phase. Under the terms of the second agreement, AbbVie and Umoja will develop up to four additional in-situ generated CAR-T cell therapy candidates for discovery targets selected by AbbVie.

"As we continue to strengthen our oncology portfolio, we believe that in-situ CAR-T cell therapy represents a paradigm shift utilizing genetic medicine concepts," said Jonathon Sedgwick, Ph.D., vice president and global head of discovery research at AbbVie. "We look forward to working with Umoja's team to advance next-generation in-situ CAR-T therapies, and potentially expand the patient populations and indications benefitting from conventional CAR-T approaches."

Umoja's VivoVec gene delivery platform combines third generation lentiviral vector gene delivery with a novel T-cell targeting and activation surface complex. This enables T cells in the body to manufacture their own cancer-fighting CAR-T cells in vivo. This has the potential to eliminate a number of challenges associated with traditional CAR-T approaches including reliance on gathering a patient's own or donor cells which are modified externally before being delivered back to the patient, the associated time lag and manufacturing challenges of ex vivo cell modification, and the need for patient's lymphodepletion.

"AbbVie is an ideal partner for Umoja given their broad expertise in development and commercialization of novel therapeutics in hematology, oncology, and beyond," said David Fontana, Ph.D., chief operating and business officer at Umoja.

"By bringing together AbbVie's like-minded pursuit of addressing patient unmet needs with our investments in vector biology and fully-owned commercial-scale manufacturing, we look forward to progressing multiple VivoVec drug candidates into the clinic in the coming years," added Andrew Scharenberg, M.D., co-founder and chief executive officer at Umoja.

Under the terms of the two agreements, Umoja received upfront payments and an equity investment from AbbVie. Additionally, for the two agreements combined, Umoja may be eligible to receive up to $1.44B in aggregate for option exercise fees, development and regulatory milestones, with the potential for Umoja to earn additional sales-based milestones and tiered royalties on worldwide net sales.

Read also: AbbVie to focus on smaller deals after buying spree

U.S. District Judge Eli Richardson in Nashville, Tennessee, ruled that Allergan plausibly alleged that Revance had acquired and used some of its rival’s trade secrets amid a series of new hires from Allergan.

Richardson said Allergan had “presented enough circumstantial evidence” to overcome Revance’s initial bid to dismiss the lawsuit, which was filed in April.

Nashville-based Revance obtained U.S. regulatory approval in 2022 for an anti-wrinkle injectable product it markets as Daxxify. Revance also separately is developing medication that is biologically similar to Allergan’s Botox.

Attorneys for Revance and a representative for the company did not immediately respond to requests for comment on Thursday.

AbbVie also did not immediately respond to a request for comment.

AbbVie acquired Botox, which launched in 2002, through its $63 billion purchase of Allergan. The drug is also approved for chronic migraine headaches and other therapeutic uses, in addition to cosmetic purposes.

Global Botox net revenue for cosmetics was $620 million in the third quarter, and $748 million for therapeutics in the same period, AbbVie reported in October.

Allergan's lawsuit alleged Revance "accelerated" a plan to recruit from Allergan regulatory professionals, in-house lawyers and sales and marketing employees who were knowledgeable about Botox and the company’s popular dermal filler Juvéderm.

The lawsuit said “it would be very challenging (if not impossible) to produce a biosimilar imitating Botox" without Allergan's confidential information.

Revance in seeking dismissal of the lawsuit said Allergan had not shown Revance had access to any of the trade secrets at issue and called the allegations "nonsensical." It said Allergan had “raced to the courthouse” after Revance won additional regulatory clearances to ramp up production of Daxxify.

Revance said in a court filing that Daxxify “represents a significant threat” to Botox.

The case is Allergan Inc v. Revance Therapeutics Inc, U.S. District Court for the Middle District of Tennessee, No. 3:23-cv-00431.

For Allergan: Jennifer Baldocchi and Eric Dittmann of Paul Hastings; and William (Zan) Blue of Constangy, Brooks, Smith & Prophete

For Revance: Katie Molloy, James Boudreau and Gregory Bombard of Greenberg Traurig

Read also: CVS Health to remove AbbVie rheumatoid arthritis drug Humira from some drug reimbursement lists in April

CVS said Hyrimoz and an unbranded version of Humira, both from Swiss drugmaker Sandoz, will be covered across all its formularies, while branded and unbranded near copies of the drug from India's Biocon will be covered on some reimbursement lists.

CVS also announced that AbbVie and CVS-owned company Cordavis, which launched in August, will produce a co-branded version of Humira that will be made available to customers in the second quarter of this year. While most biosimilars are near copies of the branded drug, the Cordavis version will be identical to Humira in its formulation, CVS said.

Unlike generic versions of easy to produce pills that are exact duplicates of the branded medicines, complex biotech drugs made from living cells cannot be exactly matched, thus the term biosimilar.

“By preferring biosimilars that have a significantly lower list price than their reference product, CVS Caremark is putting our customers in the driver’s seat to best meet the healthcare needs of their members and lower drug costs,” said David Joyner, president of CVS's Caremark pharmacy benefit division.

Pharmacy benefit managers (PBMs) act as middlemen for employers and health plans. They negotiate rebates and fees with manufacturers, and create lists, or formularies, of medications that are covered by insurance, and reimburse pharmacies for patients' prescriptions.

A CVS spokesperson said the company expects most of its customers to transition their coverage to biosimilars of Humira, known chemically as adalimumab, once the original drug is taken off formulary, although they will still have the option to cover Humira under some plans.

Humira was once the world's biggest selling prescription medicine with peak sales of $21.2 billion in 2022.

AbbVie said it had expected some payers to make formulary adjustments as more biosimilars entered the U.S. market, and that Humira remains widely available for patients alongside other adalimumab treatment options.

CVS had chosen to keep Humira on the reimbursement list it updated for Jan. 1 2024.

Although nine Humira biosimilars were launched the U.S. last year from drugmakers including Amgen, Pfizer and Boehringer Ingelheim, AbbVie has managed to retain most of the market by negotiating favorable positions on insurance drug coverage lists.

According to data from IQVIA, an average of nearly 76,000 Humira prescriptions were written per week in the second half of last year. Closest competitor Amgen averaged 417 prescriptions per week for its biosimilar Amjevita.

In July, AbbVie said it expected Humira sales to fall by two percentage points less than it had forecast at the start of the year because of those favorable insurance positions.

Three PBMs - Caremark, Cigna's Express Scripts and UnitedHealth Group's Optum Rx - control 80% of the U.S. prescription drug market.

Read also: US FDA turns down full approval of Amgen lung cancer drug Lumakras

In a statement, the authority said it had decided on Nov. 9 to launch the probe into companies including AstraZeneca, Bayer, Glaxosmithkline, Johnson & Johnson, Bausch & Lomb, Sanofi and Pfizer. It provided no further details.

Asked about the matter, AstraZeneca said it does not comment on ongoing investigations as a matter of policy.

Glaxosmithkline, Sanofi and Germany's Merck KGaA all said they were fully cooperating with competition authorities in Turkey, but did not elaborate further.

In a statement, BASF said it was assessing the matter and was committed to high standards of legal compliance and business ethics.

AbbVie, Abdi Ibrahim, Bausch & Lomb, Bayer, Ilko, Johnson & Johnson, Liba, Menarini, Michael Page International, Panasonic, Pfizer, SIFI, and World Medicine could not immediately be reached for comment.

Read also: Misrepresentation of COVID vaccine efficacy: Texas Attorney General sues Pfizer

The upfront payment will be expensed by Merck in the fourth quarter of 2023 and included in non-GAAP results.

“Caraway’s multidisciplinary approach has yielded important progress in evaluating novel mechanisms of modulation of lysosomal function with potential for the treatment of progressive neurodegenerative diseases,” said George Addona, senior vice president, discovery, preclinical development and translational medicine, Merck Research Laboratories. “We look forward to applying our expertise to build upon this work with the goal of developing much needed disease-modifying therapies for these conditions.”

Caraway is a preclinical biopharmaceutical company pursuing innovative approaches for the treatment of genetically defined neurodegenerative and rare diseases. The company has built a pipeline of novel, small-molecule therapeutics for the treatment of genetically defined neurodegenerative and rare diseases.

“This important milestone is a testament to the hard work and dedication of the Caraway team and our mission to develop therapeutics with the potential to alter the progression of devasting neurodegenerative diseases and help patients,” said Martin D. Williams, chief executive officer, Caraway Therapeutics. “This acquisition leverages Merck’s industry-leading research and development capabilities to help further advance our discovery and preclinical programs. We thank and appreciate our investors, including SV Health Investors and its Dementia Discovery Fund, AbbVie Ventures, Amgen Ventures, Eisai Innovation and MRL Ventures Fund for their support.”

Under the terms of the agreement, Merck, through a subsidiary, will acquire all outstanding shares of Caraway with earnout milestones associated with the development of certain pipeline candidates. The Board of Directors of Caraway Therapeutics has approved the transaction. Merck, through its MRL Ventures Fund, has been a shareholder of Caraway Therapeutics since 2018.

Read also: Merck gets positive EMA Committee opinion for Keytruda plus Gemcitabine, Cisplatin for Biliary Tract Cancer

The Phase III trials will soon open for recruitment.

Additional Phase II data, presented at the 59th Annual Meeting of the European Association for the Study of Diabetes (EASD), demonstrated reductions in absolute waist circumference (up to 16.0 cm), absolute body weight (up to 19.5 kg) and absolute systolic and diastolic blood pressure (up to 8.6 mmHg and 4.8 mmHg, respectively) over 46 weeks.

“As the prevalence of the disease of obesity continues to increase, it is imperative that we develop additional innovative approaches to address this serious, chronic disease,” said Carel le Roux, M.D., Ph.D., Professor at University College in Dublin, Ireland, and Principal Investigator of the trial. “Survodutide has a novel mechanism of action with the potential to reduce appetite while increasing liver energy expenditure. The promising Phase II data give us reason to be hopeful about the potential of survodutide as a treatment for people living with the disease of obesity.”

SYNCHRONIZE-1 (NCT06066515) and SYNCHRONIZE-2 (NCT06066528), now listed on clinicaltrials.gov, are Phase III studies investigating survodutide in people with obesity (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/m2) with comorbidities, including dyslipidemia, hypertension and obstructive sleep apnea. SYNCHRONIZE-1 will enrol people without type 2 diabetes (A1C <6.5%) and SYNCHRONIZE-2 will enrol people with type 2 diabetes (A1C ≥6.5%, <10%).

For both studies, the primary endpoints are percent change in body weight at week 76 and the proportion of people who achieve body weight loss of 5% or more at week 76. Secondary endpoints include body weight reductions of at least 10%, 15% and 20% at week 76. A total of 600 participants will be enroled in each of the two studies, randomized to receive weekly subcutaneous injections of either survodutide, reaching a maximum dose of 3.6 mg or 6.0 mg for maintenance treatment, or placebo.

The third study, SYNCHRONIZE-CVOT, is a Phase III trial that will enrol people with overweight or obesity with cardiovascular disease, chronic kidney disease, or risk factors for cardiovascular disease. In SYNCHRONIZE-CVOT, the primary endpoint is the time to first occurrence of any one of five major adverse cardiac events (5P-MACE): death, non-fatal stroke, non-fatal myocardial infarction, ischemia-related coronary revascularization and heart failure events.

“By implementing the valuable insights gained from the Phase II study, we are confident in the accelerated development of survodutide,” said Carinne Brouillon, Head of Human Pharma, Boehringer Ingelheim. “Obesity is a chronic disease associated with serious health complications that affects hundreds of millions worldwide. With these trial initiations, we continue to build on our heritage of bringing differentiated and innovative treatments to address cardiovascular, renal, and metabolic diseases.”

“We are excited that survodutide will shortly enter Phase III trials through the global SYNCHRONIZE program for people living with overweight or obesity,” said David Kendall, MD, Chief Medical Officer of Zealand Pharma. “With novel peptide therapeutics like survodutide, we are targeting key metabolic pathways, and these therapies have the potential to address one of the most significant healthcare challenges in medicine today.”

Read also: Boehringer unveils 81 percent discounted biosimilar of AbbVie Humira

The company said the agency did not raise concerns about the clinical trial data, safety or label for lebrikizumab, a monoclonal antibody for treatment of atopic dermatitis, or eczema.

The company said it will work with the manufacturer and the FDA to address the issues cited by the regulator in its so-called complete response letter.

A spokesperson for Lilly declined to provide more details on the findings of the FDA and the contract manufacturer.

Lebrikizumab was one of the five treatments that Eli Lilly was hoping to launch this year. The others include donanemab to treat Alzheimer's disease and tirzepatide for obesity.

It had sought approval for lebrikizumab based on three studies involving over 1,000 patients with moderate-to-severe eczema who were unable to control their symptoms with topical medicines or other systemic treatments.

Analysts, on average, estimate lebrikizumab to generate $1.64 billion in sales in 2026, according to LSEG data.

Atopic dermatitis has multiple treatments available, including those by AbbVie and Pfizer as well as some generic drugs like cetirizine

Read also: Eli Lilly settles whistleblower lawsuit over manufacturing problems

The company in July launched a branded biosimilar, Cyltezo, priced at a 5% discount to Humira's current list price of $6,922 per month. Boehringer's close-copies of Humira are the only ones that can be substituted for the original without consulting the prescriber after being designated as interchangeable by the U.S. Food and Drug Administration.

Eight Humira biosimilars from companies including Novartis unit Sandoz and Amgen were launched in the U.S. this year. Several of those companies are also seeking interchangeability status with the FDA to better compete with Humira and Cyltezo.

Until recently, Humira was the world's biggest-selling prescription drug. It had sales of $21.2 billion in 2022.

Unlike easy to manufacture pills that can be copied and sold as generics at a huge discount once patents lapse, complex biologic medicines made from living cells cannot be exactly duplicated. Their close alternatives are called biosimilars.

Boehringer executive Stephen Pagnotta said the company wanted to make a lower-cost version of Cyltezo available to pharmacy benefit managers (PBMs) looking to add cheaper Humira biosimilars on their formulary, and for healthcare systems that act as both insurer and provider and typically do not seek after-market discounts.

"We felt the dual pricing approach could really help with payers and PBMs to ensure that biosimilars are available to as many patients as possible," he said.

Pagnotta said Boehringer was in negotiations with PBMs to put the unbranded version on their lists of covered medicines over the coming months.

UnitedHealth Group's Optum RX, one of the largest U.S. PBMs, said it has already committed to covering the lower-cost version of Cyltezo on its formulary.

Sandoz and Amgen also launched Humira biosimilars with two pricing tiers. Sandoz's Hyrimoz is sold at a 5% discount to Humira's price, while its unbranded version carries an 81% discount.

Healthcare experts have said the heavily discounted versions of Humira may not be made widely available because they are unlikely to appeal to PBMs like CVS Health's Caremark, Cigna Group's Express Scripts, and Optum RX, which together control 80% of the prescription drug market.

PBMs have come under increasing scrutiny for taking some of their fees as a percentage of the discounts they negotiate for drugs they cover, which some lawmakers have said can be an incentive for favoring higher-priced medicines in their negotiations.

Read also: Eli Lilly-Boehringer Ingelheim Jardiance gets USFDA approval for adults with chronic kidney disease