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The acquisition will significantly increase Lonza’s large-scale biologics manufacturing capacity to meet demand for commercial mammalian contract manufacturing from customers with existing commercial products, and molecules currently on the path to commercialization within the Lonza network. The Vacaville (US) facility currently has a total bioreactor capacity of around 330,000 liters. Under the agreement, approximately 750 Genentech employees at the Vacaville (US) facility will be offered employment by Lonza.

Demand for capacity for commercial biologics is expected to remain high across the CDMO industry as innovative new therapies reach approval. In this context, the acquisition of the Vacaville (US) site will provide Lonza’s customers with immediate access to significant new capacity in the United States, currently the world’s largest pharmaceutical market. It will also create a significant West Coast commercial manufacturing presence, complementing Lonza’s existing Biologics site on the East Coast, in Portsmouth (US), as well as its international network across Europe and Asia.

Lonza plans to invest approximately CHF 500 million in additional CAPEX to upgrade the Vacaville (US) facility and enhance capabilities to satisfy demand for the next generation of mammalian biologics therapies. The products currently manufactured at the site by Roche will be supplied by Lonza, with committed volumes over the medium term, phasing out over time as the site transitions to serve alternative customers.

Jean-Christophe Hyvert, President, Biologics, Lonza, commented, “The Vacaville site is a highly valuable strategic acquisition that will make capacity immediately available for our customers and unlock future growth for our Biologics division. It will support us in providing a commercialization path to existing customers and incremental large-scale commercial capacity to our partners. We have deep and long-standing industrial expertise in delivering commercial scale manufacturing services for our customers’ therapies. In combining this with the strong legacy of the Vacaville facility, its highly skilled colleague community and its proven track record on quality, we are excited to take our leading large-scale mammalian offering to its next chapter of growth.”

The transaction is expected to close in H2 2024, subject to customary closing conditions. Upon closing, the Vacaville (US) site will be integrated into Lonza’s Biologics division, joining a network of existing mammalian manufacturing sites in Visp (CH), Slough (UK), Singapore (SG), Portsmouth (US) and Porriño (ES).

As the transaction is expected to be accretive to sales growth, Lonza has updated its Mid-Term Guidance 2024 – 2028. Its sales growth range was set at 11 – 13% CAGR in CER1, and has now been updated to 12 – 15%. Mid-Term Guidance for CORE EBITDA margin and ROIC remains unchanged. The Mid-Term Guidance for the net debt / CORE EBITDA ratio and CAPEX trajectory also remain unchanged.

BofA Securities are acting as financial advisors to Lonza.

OPSYNVI^® may be used in patients with PAH who are treatment-naïve or who are already on an ERA, PDE5 inhibitor or both. OPSYNVI^® may be used in patients who are currently treated concomitantly with stable doses of macitentan 10 mg and tadalafil 40 mg (20 mg x 2) as separate tablets.

PAH is a rare, progressive and life-threatening blood vessel disorder characterized by the constriction of small pulmonary arteries and elevated blood pressure in the pulmonary circulation that eventually leads to right heart failure.  An estimated 500 to 1,000 new cases of PAH are diagnosed each year in the U.S., classifying the disease as a rare condition.

The 2022 European Society of Cardiology (ESC) / European Respiratory Society (ERS) clinical guidelines recommend initial combination therapy of an ERA and a PDE5 inhibitor for patients with idiopathic PAH, heritable drug-associated PAH, or PAH-associated with connective tissue disease without cardiopulmonary comorbidities at low or intermediate risk.

“Clinical guidelines recommend treating patients with initial and sequential dual-combination therapy, regardless of risk at initial diagnosis and follow-up. Historically, this required patients to take multiple pills because no single-tablet combination therapy targeting two or more pathways was available,” said Kelly Chin, M.D., Professor of Internal Medicine and Director of the Pulmonary Hypertension Program at UT Southwestern Medical Center, and an investigator in the A DUE study.* “As administration of macitentan and tadalafil together are commonly prescribed for initial therapy for PAH, the introduction of a single tablet combining both is promising for clinicians treating patients as it may help bridge the gap between clinical guidelines and everyday clinical practice, while offering a patient-friendly approach to support initial combination therapy and rapid escalation for the appropriate patients.”

The FDA’s approval of OPSYNVI^® is based on the results from the pivotal Phase 3 A DUE study, in which OPSYNVI^® demonstrated greater reduction in Pulmonary Vascular Resistance (PVR) after 16 weeks versus tadalafil or macitentan monotherapy. OPSYNVI^® has a Boxed Warning due to the risk of embryo-fetal toxicity and requires female patients to enroll in the Macitentan-Containing Products Risk Evaluation and Mitigation Strategy (REMS) program.

With the approval, Johnson & Johnson now offers a PAH portfolio addressing all three foundational and guideline-recommended pathways – nitric oxide, endothelin, and prostacyclin.

“People with PAH often live with the burden of taking many pills each day, which can pose challenges,” said James F. List, M.D., Ph.D., Global Therapeutic Area Head, whose team oversees a portfolio of programs including Pulmonary Hypertension at Johnson & Johnson. “We’re thrilled to bring this single tablet combination therapy to patients, as it has the potential to optimize disease management and fulfill a significant unmet need in supporting recently updated treatment guidelines that call for initial or early combination treatment.”

About OPSYNVI^®

OPSYNVI^® is a combination of macitentan, an endothelin receptor antagonist (ERA), and tadalafil, a phosphodiesterase 5 (PDE5) inhibitor indicated for the chronic treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adult patients of WHO functional class (FC) II-III.

Individually, macitentan reduces the risk of clinical worsening events and hospitalization, and tadalafil improves exercise ability.

About the A DUE Study

The A DUE study was a double-blind, randomized, active-controlled, multi-center, adaptive, parallel-group study designed to compare the efficacy and safety of OPSYNVI^® to macitentan and tadalafil monotherapies in adult patients with PAH (WHO FC II or III). The three-arm trial enrolled patients from across 76 sites in 16 countries/territories worldwide who were treatment-naïve or on a stable dose of an endothelin receptor antagonist (ERA), or a phosphodiesterase 5 (PDE5) inhibitor, for at least three months. The primary endpoint was change from baseline in PVR at the end of double-blind treatment at 16 weeks and was considered met if macitentan and tadalafil fixed-dose combination (FDC) treatment was superior to both monotherapies. Following the treatment period, patients transitioned to the open-label treatment period for 24 months.

INDICATION

OPSYNVI^® is the combination of macitentan and tadalafil indicated for the chronic treatment of adults with pulmonary arterial hypertension (PAH, WHO Group I and WHO Functional Class [FC] II-III).

Individually, macitentan reduces the risk of clinical worsening events and hospitalization, and tadalafil improves exercise ability.

Short-term exposure to higher heat may increase inflammation and interfere with normal immune system functions in the body, which may, in turn, increase susceptibility to infections and accelerate the progression of cardiovascular disease, according to preliminary research to be presented at the American Heart Association’s Epidemiology and Prevention│Lifestyle and Cardiometabolic Scientific Sessions 2024, March 18- 21, in Chicago. The meeting offers the latest science on population-based health and wellness and implications for lifestyle.

Inflammation is a normal part of the body’s defenses against injury or infection, however, an inflammatory response that is longstanding-lasting weeks to months-or that occurs in healthy tissues is damaging and plays a key role in the build-up of plaque in the arteries. This may lead to atherosclerosis. Heat waves are known to promote inflammation, however, studies examining air temperature and biomarkers of inflammation have had mixed results.

“Most research only considers temperature as the exposure of interest, which may not be adequate to capture a person’s response to heat,” said lead study author Daniel W. Riggs, Ph.D., an assistant professor of medicine in the Christina Lee Brown Envirome Institute at the University of Louisville in Louisville, Kentucky. “In our study, we used alternative measurements of heat in relation to multiple markers of inflammation and immune response in the body to investigate the short-term effects of heat exposure and produce a more complete picture of its health impact.”

Participants visited study sites in Louisville during the summer months for a blood test, and researchers analyzed the blood for multiple markers of immune system function. The researchers then examined associations between the markers of immune system function and heat levels, including temperature, net effective temperature (which factors in relative humidity, air temperature and windspeed) and the Universal Thermal Climate Index (UTCI) on that day. UTCI is a thermo-physiological model developed by the International Society of Biometeorology Commission that factors in temperature, humidity, wind speed and ultraviolet radiation levels, which was used to evaluate participant’s physical comfort.

The analysis found:

• For every 5-degree increase in UTCI (in this study, the equivalent of going from a day with no thermal stress to a day with moderate thermal stress, Riggs said), there was an increase in the levels of key markers of inflammation: monocytes (4.2%), eosinophils (9.5%), natural killer T-cells (9.9%) and tumor necrosis factor-alpha (7.0%) in the blood. These immune molecules indicate activation of the body’s innate immune system, which spurs a fast and non-specific inflammatory response throughout the body to protect against pathogens and injury.
• A decrease in B-cells (-6.8%), indicating the body’s adaptive immune system that remembers specific viruses and germs and creates antibodies to fight them, was lowered.
• A lesser impact on the immune system was found when heat was measured by average 24-hour temperature or by net effective temperature, which incorporates humidity and wind but not sunshine.

“Our study participants only had minor exposure to high temperatures on the day of their blood test, however, even minor exposure may contribute to changes in immune markers,” Riggs said. “With rising global temperatures, the association between heat exposure and a temporarily weakened response from the immune system is a concern because temperature and humidity are known to be important environmental drivers of infectious, airborne disease transmission. Thus, during the hottest days of summer people may be at higher risk of heat exposure, they may also be more vulnerable to disease or inflammation.”

Adults older than age 60 and adults with existing cardiovascular disease are particularly at risk for heat-related cardiovascular events and deaths, Riggs explained. During heat waves, people can reduce their exposure by staying indoors when temperatures are highest and the sun is strongest; seeking shade; wearing light, breathable clothing; and drinking plenty of water.

“It’s important for physicians to communicate with patients about the risk of adverse health effects from heat exposure. For example, cardiologists could conduct customized consultations and assessments to increase patient awareness about their susceptibility to the effects of high temperatures. Also, changes to treatment regimens may be important to consider to address other risks. For example, some medications could make people more susceptible to heat-related illness or some may not be as effective when the body is exposed to high temperatures,” Riggs said.

Study details and background:

• Participants included 624 adults. The average age of participants was 49.5 years; 59% of participants were women; and 77% self-identified as white race.
• Data was collected in Louisville, Kentucky, from May through September of 2018 and 2019. The average 24-hour temperature on clinic visit days during the study time period was 24.5 degrees Celsius /76 degrees Fahrenheit.
• Researchers examined participants’ blood levels of cytokines (signaling molecules that may lead to inflammation); natural killer cells and tumor necrosis factor-alpha; monocytes (white blood cells); and B cells (white blood cells that produce antibodies to fight specific infections).
• Heat data, collected on the same day that participants’ blood was drawn, included 24-hour averages of temperature, net effective temperature and UTCI.
• Researchers analyzed the associations between increasing heat metrics and changes in immune system measures. The results were adjusted for several individual factors, including the participants’ age, current tobacco use and years of education.

The study’s main limitation is that it includes participants’ blood test for one single point in time. Additionally, the researchers did not know how long individuals were exposed to outdoor heat stress before their blood was drawn. Future research will include a study design to observe changes over a period of time and possibly to examine the ability of green spaces like parks to reduce the harmful effects of high temperatures on inflammation in the body.

Reference:

Heat exposure may increase inflammation and impair the immune system, American Heart Association, Meeting: AHA EPI|Lifestyle Scientific Sessions 2024.