The two companies are in arbitration to decide what Sanofi's obligations might be, given Sanofi acquired the marketing rights to Zantac from Boehringer in 2017. A decision was initially expected by the end of 2022. Now, Sanofi sees it sometime this year, and at the end of the first quarter at the earliest."Obviously as with all arbitrations, this is a completely closed process so there's no way to know if this means anything in any way at all," Barclays analyst Emily Field said. Sanofi's shares were up nearly 1 percent in morning trade, hitting highs last seen in August earlier in the session.Thousands of US lawsuits claiming Zantac caused cancer have been disputed by the plethora of drugmakers that have sold either the branded or generic version of the drug since it was initially approved in 1983 and went on to become one of the first medicines to top $1 billion in sales.Originally marketed by a forerunner of GSK, the medicine has been sold at different times by companies including Pfizer, Boehringer, and Sanofi as well as several generic drugmakers. Last month, a federal judge knocked out about 50,000 claims on the basis they were not backed by sound science. Later in December, Bloomberg reported Sanofi and Pfizer had settled a claim in California.Read also: Cancer Litigation over Zantac: US Court gives relief to pharma cos, dismisses thousands of lawsuits"Sanofi settled this case not because it believes these claims have any merit, but rather to avoid the expense and distraction of a trial in California," it said. On Wednesday, Sanofi also said it expected fourth-quarter results next month to benefit from a stronger dollar and flu vaccine sales.The drugmaker, which reports results in euros, made more than 40 percent of its sales in the first three quarters of 2022 in the United States. The preliminary estimate is for currency movements to have boosted fourth-quarter sales by 4.5-5.5 percent and core earnings per share by 6-7 percent, Sanofi said.Barclays' Field said there was not much to read into this, other than that the foreign exchange impact was a bit lower in the fourth quarter than expected for the full year. She added most people focused on organic growth, which strips out currency moves.

The U.S. Court of Appeals for the Federal Circuit upheld a decision rejecting Genentech's bid to block the generic idiopathic pulmonary fibrosis (IPF) drug.

The Federal Circuit said Sandoz's drug would not infringe Genentech patents related to methods for managing side effects while using Esbriet. Other patents Genentech accused Sandoz of infringing were invalid, the appeals court said.

Representatives for both Genentech and Sandoz declined to comment, citing ongoing litigation.

San Francisco-based Genentech's Esbriet is used to treat IPF, a serious chronic lung disease. Roche earned over $1 billion last year from worldwide Esbriet sales.

Genentech sued Switzerland-based Sandoz and several other drugmakers, including Amneal Pharmaceuticals Inc and Teva Pharmaceutical Industries Ltd, for patent infringement in 2019 over their proposed Esbriet generics. Sandoz defeated Genentech's lawsuit against it in Delaware federal court in March and launched its generic in May.

Read also: Roche, Chugai Pharma to transfer Bonviva business in Japan to Taisho Pharma

The Federal Circuit agreed with the district court that Sandoz's generic would not infringe patents covering ways to avoid adverse interactions between Esbriet and another drug. It also upheld the decision that some of Genentech's patents were invalid.

"Varying doses in response to the occurrence of side effects would seem to be a well-established, hence obvious, practice," the appeals court said. "Thus, claiming it as an invention would appear to be at best a long shot."

Read also: Submit Phase IV CT protocol: CDSCO Panel tells Roche over Anti-Cancer drug Pralsetinib

The case is Genentech Inc v. Sandoz Inc, U.S. Court of Appeals for the Federal Circuit, No. 22-1595.

For Genentech: Daralyn Durie of Durie Tangri

For Sandoz: William Jay of Goodwin Procter

Read also: Roche Actemra gets USFDA okay to treat COVID in hospitalised adults

Politico, which first reported on AbbVie's exit, said the drugmaker was also leaving the industry group Biotechnology Innovation Organization as well as Business Roundtable, citing a person with knowledge of the matter.

A source familiar with the matter confirmed Reuters about the exits in the Politico report.

Drugmakers suffered a rare defeat earlier this year in failing to stop a bill that allows the government to negotiate prices on select drugs.

Reuters reported in August the pharmaceutical industry spent at least $142.6 million on lobbying Congress and federal agencies in the first half of 2022, more than any industry.

President Joe Biden's signature Inflation Reduction Act will allow the government to choose 10 drugs to negotiate from among the 50 costliest ones for Medicare, the government healthcare program for people aged 65 and older or disabled, starting in 2026.

Read also: Abbvie RINVOQ gets European Commission nod for treatment of Active Non-Radiographic Axial Spondyloarthritis in adults

AbbVie said it regularly evaluated its memberships with industry trade associations and decided not to renew with select trade associations, without naming the groups.

"AbbVie has decided not to renew their membership with PhRMA in 2023. This does not change our focus on fighting for the solutions patients and our health care system need," PhRMA spokesperson Brian Newell said.

Read also: AbbVie receives EMA Committee positive opinion for Crohn's Disease treatment Risankizumab

For years Merck has relied on Keytruda to fuel its growth. The treatment, approved in 2014, harnesses the body's own immune system to fight cancers with dramatic results. Against advanced lung cancer, it has led to a five-year survival rate in about one-quarter of people compared to 5% of people historically.But the key patents on Keytruda will begin to expire in 2028, opening the door to biosimilars - near copies of expensive biologic drugs whose complex molecules cultivated inside living cells make it impossible to manufacture exact copies.Merck is testing in clinical trials two versions of the drug that can be injected subcutaneously, a quick alternative to infusions, the current delivery method in which patients receive an intravenous drip in a health office once every three or six weeks. The company reported early data from one of those trials last year.While Merck has disclosed that it is developing subcutaneous versions of Keytruda, it has not previously said that it expects the new formulation to become the most widely used version of the drug after it is rolled out and an engine for growth toward the end of the decade.If successful, Merck could begin marketing the new formulation within a few years, a top Merck executive told Reuters. It expects it to fuel Keytruda's growth as it gains approvals in earlier stage cancers. Keytruda now accounts for more than one-third of Merck's sales."We believe that subcutaneous formulation has the potential to be novel, non-obvious and useful, which means we would get a new patent for it," Merck CFO Caroline Litchfield said in an interview, using the terminology for the criteria under U.S. law to determine what technologies merit a patent."The clock for that patent would start ticking from the time we would get that patent approved."While some patients would likely still receive the original formulation if it is being administered along with chemotherapy or other intravenous drugs, the subcutaneous formulation could replace the IV version for most patients, Merck Chief Medical Officer Eliav Barr told Reuters."In theory it could replace everywhere that Keytruda currently is used," Barr said.Drug patents have a guaranteed term of exclusivity for 20 years after receiving a patent under U.S. law, but sometimes the companies are able to add additional patents that extend their exclusivity.For example, the primary patent on Abbvie's arthritis drug Humira expired in 2016 but the drug will not face U.S. competition until 2023, in part because the company eventually received more than 130 patents that protect the drug.Merck's patents on the subcutaneous version of Keytruda could protect that formulation until at least 2040, according to Tahir Amin, co-founder of drug patents watchdog group Initiative for Medicines, Access & Knowledge (I-MAK)."It's the way the pharmaceutical companies now use that system -- it's all about taking up as much space as possible, making it difficult for anybody to enter," Amin said. "Keytruda is going to be the next Humira by all accounts."Asked whether it was motivated more by patent issues than medical need, Merck said it was continuously focused on improving Keytruda and getting it to more patients.Merck said it may seek patents for innovations in how the drug is used, its formulation, the size and schedule of doses and combinations with other drugs."These patent applications, if granted, may provide varying degrees of protection beyond 2028. However, we would continue to point to late 2028 as the most likely timeframe for biosimilar entry into the market," Merck said in a statement.DO PATIENTS PREFER SHOTS?Getting doctors and hospitals to adopt the new formulation before biosimilar competition arrives could help Merck protect more of its Keytruda revenue for longer but is not certain, analysts said. On average, they expect Keytruda revenues to top $30 billion in 2026 and $35 billion by 2028, according to Refinitiv data. "Theoretically, in the US, they could transition all of the market," Mizuho analyst Mara Goldstein said, "depending on how quickly they can get it to market."However, BMO Capital's Evan Seigerman said that private insurers in the U.S. might balk at paying for the more expensive branded product and prefer a biosimilar infusion version. Still, he believes the new formulation could allow the company to hold onto as much as 20 percent of its Keytruda revenue into the 2030s.Two doctors interviewed by Reuters said they were not convinced that the new route of administration represents a significant enough clinical improvement over IV infusions to justify the additional system-wide healthcare costs that might be a product of Merck receiving a new patent."I don't think it's going to improve the safety or the effectiveness of the drug," said Dr. Shailender Bhatia, an oncologist at the Fred Hutchinson Cancer Center in Seattle.Merck's Barr said the easier-to-use formulation of the drug could help patients' health by keeping them on Keytruda and on schedule, and could keep high-risk cancer patients from spending long times in hospital settings where they could be exposed to other diseases."From a quality of life and patient perspective, it's for sure going to be helpful," Barr said.That view is backed by clinical studies that have found that patients prefer subcutaneous injections to intravenous administration which can be time-consuming and invasive.How much hospitals and doctors embrace the method could reflect how they will be impacted by the change financially.Hospitals are typically paid less to administer an injection than a long infusion. That could be offset somewhat if the drug's price is higher, since providers receive a percentage fee for physician-administered drugs, according to Lisa Mulloy, chief pharmacy officer for New York's Northwell Health hospital system.Merck said it would not speculate on the expected price of pipeline products. The infusion's list price is about $185,000 per year, though the drug may cost less with company discounts.Northwell's Mulloy said moving patients to subcutaneous versions of drugs also opens up spots in infusion centers for additional patients.

Read also: Merck lifts full-year forecast as cancer immunotherapy Keytruda sales soar

Roche presented full results of twin trials at an Alzheimer's meeting in San Francisco after announcing in November that the drug had failed in the two trials.

Unlike Eisai Co Ltd and Biogen Inc's lecanemab, which appears to be on track for U.S. regulatory approval after presenting successful trial results on Tuesday, Roche's drug did not show a statistically significant benefit in patients with mild cognitive impairment and early Alzheimer's disease.

Both drugs are designed to remove forms of the protein beta amyloid from the brain, sticky plaques believed to play a major role in the disease.

While Eisai's infusion succeeded in slowing the advance of Alzheimer's by 27% after 18 months, Roche's drug reduced decline by just 8% in the Graduate I study and 6% in the Graduate II study compared with a placebo after two years.

A key difference may have been in the drug's ability to clear amyloid from the brain.

In a presentation on Wednesday, researchers said gantenerumab, which is given by injection, only achieved amyloid clearance in 28% of patients in the Graduate I trial and 25% in Graduate II after two years, half of what the company expected to see.

Lecanemab, by contrast, cleared amyloid in 68% of those in the study after 18 months.

Dr. Howard Fillit, chief science officer at the Alzheimer's Drug Discovery Foundation, said there are a number of reasons why Roche's drug may have failed, including differences in chemistry, dosing, and the way it was administered via injection versus infusion.

But the fact that the drug failed to remove amyloid deposits in the brain as expected clearly played a role, he added.

The field of Alzheimer's research is littered with failure and disappointment, including for several drugs in the same class, and previous efforts to prove gantenerumab's worth.

In 2014, the drug failed to show a benefit when given at a lower dose among patients with mild Alzheimer's, and it failed again in 2020 in a Washington University School of Medicine trial of patients with an inherited form of Alzheimer's.

"Obviously, within the class, some drugs are working and some aren't," Fillet said.

A Roche spokesman said in an emailed statement that the company will stop all gantenerumab studies in early Alzheimer's disease, including extension studies of the Graduate trials and the Skyline Phase III study in patients with evidence of amyloid in the brain but no signs of cognitive decline.

"In the Graduate studies, the level of amyloid removal was lower than expected. We expect the same, lower effect in the Skyline population, and consider this insufficient to continue," the spokesman said.

Roche is still testing a different formulation of gantenerumab called trontinemab, designed to ferry the drug across the blood-brain barrier - protective blood vessels that prevent chemicals in the bloodstream from entering the brain - in hopes of getting more of the treatment into the brain.

"We remain committed to Alzheimer's disease and will direct our focus to new and potentially improved approaches for new treatments," Rachelle Doody, Roche's global head of neurodegeneration drug development, said in a statement.

Read also: Roche Alzheimer's drug gantenerumab fails to meet goal in long-awaited trial

Mumbai: Pharma major Cipla Limited and its wholly owned subsidiary Cipla USA Inc., today announced the launch of Leuprolide Acetate Injection Depot
22.5mg in US.

The product was approved by the United States Food and Drug
Administration ("US FDA") based on a New Drug Application (NDA) submitted under
the 505(b)(2) regulatory pathway.

Leuprolide Acetate Injection Depot contains 22.5 mg of leuprolide acetate for 3-
month administration given as a single dose injection.
It is supplied as lyophilized microspheres in a single dose vial as a kit with a prefilled
syringe containing 2mL 0.8% mannitol solution and an easy-to-use MIXJECT transfer
device for a single dose injection.

It is indicated for the palliative treatment of advanced
prostate cancer.

Read also: Conduct Active Surveillance Study: CDSCO Panel tells Cipla on Idiopathic Pulmonary Fibrosis Drug Pirfenidone tablet

Arunesh Verma, CEO – Cipla North America, said, "The launch of Leuprolide Acetate
Injection Depot reinforces our commitment as an organization to bring high quality
and affordable treatments to patients in the US. Enabling access to high-quality
treatments is core to our purpose of "Caring for Life". This launch aligns with our
strategy for growth in the complex product segment."

The active ingredient, route of administration, dosage form, and strength are the same
as LUPRON DEPOT 22.5 mg strength, from Abbvie. According to IQVIA, LUPRON
DEPOT 22.5mg had US sales of approximately $197M for the 12-month period ending
September 2022.

Read also: Cipla gets CDSCO Panel nod to manufacture, market COPD drug combination Aerosol for inhalation

Cipla Limited is an Indian multinational pharmaceutical and biotechnology company headquartered in Mumbai, India. The Company was founded by Khwaja Abdul Hamied in 1935 in Mumbai.

Cipla primarily develops medicines to treat respiratory, cardiovascular disease, arthritis, diabetes, weight control, depression, and other medical conditions.

Read also: Dr Reddy's Labs, Cipla facilities join World Economic Forum Global Lighthouse Network

Under the deals, first announced in July, Israel-based Teva will pay up to $4.25 billion, including a supply of the overdose drug naloxone. AbbVie will pay up to $2.37 billion. The final amounts of the settlements will depend on how many state and local governments opt into them.

Lead attorneys for state and local governments in a joint statement called the deals "significant steps forward in our continued efforts to hold those responsible for the opioid epidemic accountable and obtain the necessary resources to battle its catastrophic effects."

Read also: Abbvie RINVOQ gets European Commission nod for treatment of Active Non-Radiographic Axial Spondyloarthritis in adults

Teva and AbbVie did not admit wrongdoing. The two companies said that as part of the settlements, they have resolved a dispute between them over responsibility for claims stemming from generic opioid business that Allergan sold to Teva in 2016.

The sprawling litigation over opioids, which began in 2017, has yielded more than $40 billion in settlements with drugmakers, distributors, and pharmacy chains.

Read also: AbbVie receives EMA Committee positive opinion for Crohn's Disease treatment Risankizumab

State and local authorities have said they will use the money to combat the opioid crisis, which according to federal government data has caused nearly 650,000 overdose deaths since 1999 and is continuing to worsen.

Overdoses involving opioids, including prescription pills and heroin, surged during the COVID-19 pandemic, increasing 38% in 2020 over the previous year and another 15% in 2021, according to the U.S. Centers for Disease Control and Prevention.

Read also: AbbVie to pay up to USD 2.37 billion to resolve US opioid claims

Japan: Takeda has announced that the U.S. Food and Drug Administration (USFDA) has accepted and granted priority review of the Biologics License Application (BLA) for TAK-003, the company's investigational dengue vaccine candidate. In the U.S., TAK-003 is being evaluated for the prevention of dengue disease caused by any dengue virus serotype in individuals 4 years through 60 years of age.

Dengue is a mosquito-borne virus endemic in more than 125 countries, including the U.S. territories of Puerto Rico, the U.S. Virgin Islands and American Samoa. Incidence of dengue has increased globally over the past two decades and is a leading cause of fever among travelers returning from Latin America, the Caribbean and Southeast Asia.

"If approved, we believe TAK-003 has the potential to become an important dengue prevention option for healthcare providers, and we continue to be encouraged by our discussions with the FDA," said Gary Dubin, M.D., president of the Global Vaccine Business Unit at Takeda. "This year, of the 888 dengue infections in the U.S., 96% were a result of travel to dengue endemic areas. Of the 316 dengue infections in U.S. endemic territories, 97% were locally transmitted. At Takeda, we are guided by our commitment to serving these affected populations and are fully committed to working with the FDA to advance this filing."

Takeda's tetravalent dengue vaccine candidate (TAK-003) is based on a live-attenuated dengue serotype 2 virus, which provides the genetic "backbone" for all four vaccine viruses.

The TAK-003 BLA is supported by safety and efficacy data from the pivotal Phase 3 Tetravalent Immunization against Dengue Efficacy Study (TIDES) trial, where the dengue vaccine candidate met its primary endpoint by preventing 80.2% of symptomatic dengue cases at 12 months. In addition, TAK-003 met its secondary endpoint by preventing 90.4% of hospitalizations at 18 months, and in an exploratory analysis, it demonstrated protection against dengue fever through 4.5 years (54 months) after vaccination. The TIDES exploratory analyses showed that throughout the 4.5-year study follow-up, TAK-003 prevented 84% of hospitalized dengue cases and 61% of symptomatic dengue cases in the overall population, including both seropositive and seronegative individuals.

Currently, TAK-003 has not been approved by the FDA or any other health authority outside of Indonesia. In October 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended the approval of Takeda's dengue vaccine candidate, TAK-003, for the prevention of dengue disease caused by any serotype in individuals four years of age and older in Europe and in dengue-endemic countries participating in the parallel EU-M4all procedure. The final step in the path to approval in Europe is a Marketing Authorization decision from the EMA, which is expected in the coming months. Regulatory reviews will also progress in dengue-endemic countries in Latin America and Asia.

Read also: Takeda gets positive CHMP opinion recommending nod of Dengue Vaccine in EU, Dengue-endemic countries

More than 55 brand-name blockbuster biologic drugs, each with peak annual sales above $1 billion, are due to come off patent by the end of the decade, according to industry estimates.

Executives from Teva, and Sandoz said they are targeting top-selling biologics such as Humira, AbbVie Inc's top-selling arthritis drug, which came off-patent in Europe and is due to come off-patent in the U.S. next year. But both companies face commercial and regulatory challenges, especially in the U.S., where biosimilars have not resulted in dramatically lower prices for consumers.

Biologics are complex molecules cultivated inside living cells, making it impossible to manufacture exact copies, as is the case with conventional pharmaceuticals made from chemical compounds.

Use of brand-name biologics typically account for an outsize proportion of drug spending in wealthier countries.

One of the biggest makers of generic drugs, Israeli-based Teva said it aims eventually to secure a 10% global market share of biosimilars. The company has been grappling with a heavy debt load since a 2016 acquisition and lawsuits arising from the U.S. opioid epidemic.

Teva currently has three approved biosimilars and 13 in development.

"We are going full blast now," Teva Chief Executive Kåre Schultz said in an interview with Reuters.

He said the company was targeting "80% of what's going off-patent in the next 10 years" including big sellers like the cancer drug Keytruda.

A division of Novartis, Sandoz is currently the second biggest player after Pfizer Inc in the biosimilar market by gross sales globally, per IQVIA data, cited by Sandoz. (Amgen is in third place).

Sandoz has launched eight biosimilar drugs.

"We now have over 15 products in development, and in the next five years we would like to double the value of our marketed portfolio," chief scientific officer Claire D'Abreu-Hayling told Reuters, adding that the biologics they intend to target are "really obvious opportunities".

BLOCKBUSTERS COMING OFF PATENT

Novartis plans to spin off its Sandoz generics business in 2023. The Swiss drugmaker said the unit failed to attract a serious buyer earlier this year as it considered options for the unit's future.

The more than 55 blockbuster biologics coming off patent protection in the United States and Europe over the next decade account for more than $270 billion in expected peak annual sales, according to a McKinsey analysis.

The analysis projected the value of the global biosimilar market could more than triple to an estimated $74 billion by 2030.

Next year could bring a test case in the U.S. market, with the anticipated launch of at least six biosimilars for Humira, which brings in about $15 billion to $20 billion in annual sales and is approved for autoimmune conditions including rheumatoid arthritis, psoriasis and Crohn's disease.

Sandoz and Teva are both working on biosimilars for Humira.

But the crowded field raises a tough question: Should the companies target the biggest selling biologics such as Humira, or aim for smaller brands that will likely attract fewer players, said Barclays pharmaceuticals analyst Emily Field.

Teva aims to ensure it is one of the first three biosimilars on the market for any given biologic, according to Sven Dethlefs, executive VP, North America commercial. He said the company intended to kick off multiple biosimilar development programs but would halt production if it could not make the top three.

While going after Humira, Sandoz is also targeting drugs like Biogen's multiple sclerosis medicine Tysabri, which is used in a much smaller patient population. The company believes no other biosimilar is being actively developed for Tysabri, said Chief Operating Officer Pierre Bourdage.

Creating the only biosimilar in a particular market for a particular drug could be a win, said Joshua Harris, senior VP focused on pharmaceutical patent litigation at Burford Capital, a provider of commercial legal finance. "That's going to be a rare situation," he said.

A typical biosimilar costs $100 million to $300 million to develop and between six to nine years to win approval, according to McKinsey. About half of efforts launched across the U.S., European, and Japanese markets fail at the earliest stages, the report found.

Generics, which can be priced as much as 80% to 90% less than branded pills, barely cost a few million to develop.

Biosimilars are viewed as "better than traditional generics, but nowhere near as good as branded pharma," Field said.

Commercial prospects will also depend on the regulatory environment. While more than 50 biosimilars have been introduced into the European market, the United States has taken longer to set up a regulatory pathway for biosimilars.

European regulators consider all approved biosimilars on par with the original biologic, which has helped boost uptake. Biosimilars have taken the majority of market share from brand-name biologics in Europe and resulted in savings between 75% to 90% off the reference product prices, according to a 2021 report by Duke University's Margolis Center for Health Policy.

In the United States, the Food and Drug Administration (FDA) has approved 39 biosimilars and 22 products have been launched as of October, according to an Amgen analysis.

The FDA typically expects additional trial data before designating a biosimilar as "interchangeable" with the original biologic, which would allow it to be automatically replaced with a biosimilar at the pharmacy counter.

In a note last month, SVB Securities analysts predicted most U.S. payers will likely stick with branded Humira next year, but seriously consider switching patients to interchangeable biosimilars by 2024.

Biosimilars launched in the U.S. have only taken about 20% of the volume share of the biologics they are based on, according to the Duke Report, with knockoffs delivering discounts of about 30% to 40%.

Patent-focused court battles have stymied some launches of biosimilars. Aggressive pricing strategies from branded drug companies also helped neutralize the limited discounts initially offered by biosimilar makers

Read also: Former Sandoz Chief Richard Francis joins Teva Pharma as President, CEO