January 2024 industry update

Keywords: :

• biotechnology
• cell and gene therapy
• innovation
• targeted drug delivery

1. Company news

1.1. Big pharma at crossroads navigating impending patent expiration on blockbuster drugs

Major pharmaceutical companies such as Merck (Darmstadt, Germany), Bristol Myers Squibb (NY, USA) and Johnson & Johnson (NJ, USA) are preparing for potential revenue losses as their blockbuster drugs face patent expirations and increased competition from generics and biosimilars. These companies have historically relied on a few key drugs for a significant portion of their revenue, but as these patents expire, they anticipate a decline in profits. Merck, for example, is bracing for the loss of exclusivity for its humanized antibody Keytruda, while Bristol Myers Squibb faces patent expirations for its blood thinner Eliquis, and Johnson & Johnson prepared for patent expiration for their immunosuppressive medication Stelara. To offset these revenue declines, these companies are investing in research and development for new drugs and exploring partnerships and acquisitions to bolster their portfolios. Additionally, they are implementing cost-cutting measures and restructuring efforts to maintain profitability. Despite the challenges, analysts remain cautiously optimistic about the industry's ability to innovate and adapt to changing market dynamics. Finally, the Medicare Drug Price Negotiation Program facilitated by the Inflation Reduction Act poses an extra challenge to pharmaceutical companies in the USA. However, the program will benefit patients by lowering drug costs and expanding benefits for generations to come [1,2].

1.2. Riding the wave of topical corticosteroids market boom

According to Technavio's report, the global topical corticosteroids market is expected to grow steadily during the forecast period of 2023–2027, with a compound annual growth rate of around 4%, equating to USD $1.08 billion. Moreover, the report included a detailed market analysis of leading pharmaceutical companies including AstraZeneca (Cambridge, UK), Bayer (Leverkusen, Germany), Eli Lilly (IN, USA), GlaxoSmithKline (Brentford, UK), Novartis (Lonon, UK), Pfizer (NY, USA), Sanofi (Paris, France), Teva (Tel Aviv, Israel) and others. The primary drivers of the expected growth are the increasing prevalence of skin disorders, such as eczema, psoriasis and dermatitis. Additionally, the rising geriatric population and the growing awareness about skincare are expected to contribute to market expansion. Finally, manufacturers are focusing on developing innovative formulations with improved efficacy, safety profiles and patient compliance. Despite this, the market still faces challenges such as potential side effects, regulatory restrictions, and the availability of generic alternatives. North America currently dominates the market due to the high prevalence of skin disorders and the presence of key market players. Still, the Asia-Pacific region is expected to witness significant growth during the forecast period, driven by improving healthcare infrastructure and rising disposable incomes in emerging economies [3].

1.3. Scaling up: Novo Nordisk's efforts to meet demand for Wegovy weight-loss drug

Novo Nordisk (Bagsvßrd, Denmark), the manufacturer of Wegovy (semaglutide), the popular GLP-1 receptor agonist indicated for weight loss, has announced plans to increase the availability of the medication for individuals in USA. Due to the supply shortages caused by high demand, the company had restricted access to starter doses of Wegovy as of May 2023. Doug Langa, head of the North American operations for Novo Nordisk, stated that the company are now expanding the availability of lower dose strengths of Wegovy to more than double the previous allocations, and aim to continue ramping overall supply throughout 2024. However, Novo Nordisk faced supply shortages shortly after approval due to high demand. To address this, the company engaged with new manufacturers to expand its supply chain and are investing approximately USD $6.5 billion in production in 2024, nearly double the previous year's investment. Despite these efforts, Novo Nordisk acknowledges that demand will likely continue to outpace supply, and may continue to cause difficulties for patients receiving Wegovy prescriptions [4,5].

2. Collaborations & agreements

2.1. Australia to Invest AUD $50 million to pioneer artificial heart to beat heart failure

The Australian Government is injecting AUD $50 million into the Artificial Heart Frontiers Program (AHFP), an initiative to develop a world first total artificial heart in the hopes of cutting global heart failure mortality by half. The Medical Research Future Fund will support the AHFP, which comprises a consortium of five universities, three clinical partners and the medical device company, BiVACOR (CA, USA). The fund will be directed to the development of three cutting edge technologies to form the Total Artificial Heart, including an implantable heart pump using state-of-the-art magnetic levitation technology, a left ventricular assist device and small implantable mini pumps.

Mark Butler, the Australian Minister for Health and Aged Care added, “As well as the obvious health benefits, this is an incredible story of Australian ingenuity and sovereign manufacturing, with collaboration across universities, clinical hospitals and industry to develop the world's most advanced artificial heart”. Indeed, the AHFP will not only improve patients' outcomes and quality of life but seeds a pipeline for commercialization with a new specialized Australian industry [6,7].

2.2. AbbVie's Neurology Expansion as a Billion-Dollar Bet on Cerevel's Pipeline

AbbVie (IL, USA) has entered into a definitive agreement to purchase Cerevel Therapeutics (MA, USA) and its neuroscience pipeline for an estimated USD $8.7 billion. Cerevel's pipeline comprises various clinical-stage and preclinical candidates targeting neurological diseases like schizophrenia, Parkinson's disease and mood disorders. Among Cerevel's assets in clinical development is the antipsychotic drug emraclidine, currently undergoing Phase II trials for schizophrenia. The drug has also shown potential in dementia-related psychosis linked to Alzheimer's and Parkinson's diseases. AbbVie views this acquisition as complementary to its existing neuroscience portfolio, broadening its range of assets addressing psychiatric and neurological disorders with unmet medical needs. Richard A Gonzalez, AbbVie's chairman and CEO, sees substantial growth potential through the combined pipeline with Cerevel well into the next decade. This marks AbbVie's third recent acquisition announcement, with the transaction expected to be completed by mid-2024, subject to approval from Cerevel shareholders, regulatory clearance and customary closing conditions [8,9].

3. Approvals & regulatory updates

3.1. First & only gene therapy treatment for hemophilia B HEMGENIX (CSL) approved by Swissmedic

HEMEGENIX (CSL) is the first and only gene therapy approved for the treatment of moderate to moderately severe haemophilia B for adult male patients. The approval from Swissmedic, Switzerland's national therapeutic products agency, follows promising data out of the Phase III HOPE-E trial, which reports the capacity of HEMEGENIX to reduce annual bleeding rates through the single dose gene therapy. The treatment utilizes the adeno-associated virus type 5 (AAV5) vector to deliver a functional coagulation factor IX gene to liver cells. This enables the body to endogenously produce 5–eight-times more factor IX protein than prior to treatment, as well as stabilize systemic levels. This new innovative treatment option improves current treatment standards and the quality of life for most patients who typically undergo prophylactic factor IX infusions. Swissmedic joins its global counterparts, the European Medicines Agency, the FDA, Health Canada, and the UK Medicines and Healthcare products Regulatory Agency, who have approved or conditionally authorized HEMEGENIX [10,11].

3.2. Amtagvi approved by FDA as first cell-based therapy for advanced melanoma

In another new-drug approval, the FDA has approved Amtagvi (lifileucel) as the first cell-based therapy for adult patients with solid tumor cancer, namely unresectable or metastatic melanoma. Amtagvi poses an alternative treatment for patients who have unsuccessfully trialed systemic therapy, such as PD-1 blocking antibodies and BRAF inhibitors with or without an MEK inhibitor (if positive for BRAFV600 mutation). Instead, Amtagvi is an autologous tumor-derived T-cell immunotherapy utilizing a patients tumor-infiltrating lymphocytes (TILs). TILs are harvested from surgically removed tumor tissue and further expanded in a manufacturing center. They are then reinfused back to patients in masses. The developers from Iovance Biotherapeutics (CA, USA) were finally granted approval for Amtagvi through the accelerated approval pathway, following prolonged struggles with US FDA regulations regarding the TIL's polyclonal nature and lack of predefined target. Amtagvi is priced at USD $515,000 per patient for the one-time infusion; the most expensive of any cell-based cancer therapy in USA, with CAR-T cell therapies closely behind at USD $500,000 [12–14].

3.3. Johnson & Johnson's DARZALEX FASPRO^® Quadruplet therapy seeks approval from US FDA

Johnson & Johson recently submitted a supplemental Biological Licence Application (sBLA) to the US FDA which may see DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) incorporated as a quadruplet combination therapy for patients with newly diagnosed multiple myeloma who are eligible for an autologous stem cell transplant. DARZALEX FASPRO will be indicated for induction and consolidation treatment with bortezomib, lenalidomide and dexamethasone, in conjunction with lenalidomide for maintenance treatment. The sBLA is supported by data from the PERSEUS Phase III trial showing a reduced risk of disease progression or death by 58% when DARZALEX FASPRO quadruplet treatment regimen was administered in comparison to the standard treatment without DARZALEX FASPRO. The Vice President of Johnson & Johnson, Craig Tendler, stated, “…this regimen has the potential to improve long-term outcomes for newly diagnosed patients and we look forward to working with the FDA on the review of this application” [15].

3.4. EMA's green light for Biogen's ALS breakthrough, Qalsody

Recently, the European Medicines Agency (EMA) recommended granting marketing authorization to Biogen's (CA, USA) drug for amyotrophic lateral sclerosis (ALS), a deadly and progressive neurodegenerative disease. Known as Qalsody, the drug had previously received accelerated approval in USA in April 2023. Qalsody targets a rare genetic form of ALS caused by the accumulation of toxic SOD1 protein, estimated to affect about 2% of ALS patients. This approval was based on preliminary data indicating its efficacy in reducing levels of a neurofilament protein associated with disease progression. The same trial, which involved 108 patients, also served as the basis for the European Union's (EU) more recent recommendation. However, Biogen must still verify the drug's benefits in a post-approval trial, as required by both US and EU regulators. Currently, the only authorized treatment for ALS in the EU is the generic drug riluzole. The EMA highlighted the urgent need for effective therapies to preserve muscle function and prolong the life expectancy of ALS patients. The European Commission will review the EMA's recommendation, with a decision expected in the second quarter of 2024 [16–18]

4. Clinical trials

4.1. CAR-T cells take new road down autoimmune & neurodegenerative diseases

A US first clinical trial for CAR (chimeric antigen receptor)-T cell therapy as a therapeutic option for multiple sclerosis (MS) has begun recruiting volunteers in the hopes of repurposing CAR-T cells for neurodegenerative and autoimmune diseases. While CAR-T cell therapies are traditionally indicated as immunotherapies for several blood cancers, researchers are hoping to capitalise on their B cell targeting capacity to target CD19 expressing B cells in the pathology of MS, and to potentially reset the immune system. California (USA) based biotechnology firm Kyverna Therapeutics is spearheading the project, noting that CAR-T cells are better B-cell killers than the currently available antibody treatments, and can have enhanced penetration in brain tissue for targeted delivery. This project is in partnership with a Phase I trial at Stanford University (CA, USA), however concurrent studies are already underway in Germany with a small clinical trial for CAR-T cell therapy for patients with MS. More recently, a research group from the Bavarian Cancer Research Centre disseminated positive findings at the American Society of Haematology meeting in December 2023 for CAR-T cell therapy in autoimmune diseases. 15 patients with systemic lupus erythematosus, idiopathic inflammatory myositis or systemic sclerosis were treated with a single infusion of CD19 CAR-T cells which achieved rapid elimination of CD19⁺ B cells and persistent drug-free remission. Drug developers are watching this space closely as an opportunity to advance a pipeline of CAR-T cell therapies for autoimmune diseases, albeit with safety and efficacy concerns in mind [19–21].

4.2. Omalizumab offers hope for severe food allergy management

Omalizumab, a monoclonal antibody therapy, demonstrated significant efficacy in reducing allergic reactions among individuals with multiple severe food allergies in recent late-stage trials, as reported by two research groups from Denmark and USA. Omalizumab is an anti-IgE acting drug with the capacity to increase the threshold of a patient's reactivity to food allergens and protect against allergic reactions. Originally approved for asthma treatment, omalizumab now offers a potential solution for individuals with severe food allergies. Following treatment with omalizumab, a notable percentage of participants demonstrated increased tolerance to allergen exposure. For example, about two thirds of those receiving omalizumab could consume the equivalent of about four peanuts without experiencing moderate to severe allergic reactions, compared with less than 10% in the placebo group. Similar improvements were observed with other allergens, such as cashews and milk. The lead investigator of the US study, Robert Wood, emphasized that while individuals will still need to avoid allergenic foods, the medication can alleviate concerns about inadvertent consumption of trace amounts of these foods [22–24].

5. Early-stage developments

5.1. Drugs on-demand

A breakthrough in transdermal drug delivery was recently published in Nature Communications showcasing an electrically activated dermal patch for personalized and precision drug delivery. The novel spatiotemporal on-demand patch (SOP) is a skin interfaced platform which combines biocompatible metallic microneedles with electrical stimulation from wireless devices (such as low energy Bluetooth) to trigger on-demand transdermal drug release. This treatment modality not only provides a convenient and personalized release profile, but also ultrafine spatiotemporal controllability of drug release (<1 mm²). The authors Wang et al. demonstrated safe and efficacious intracranial delivery of melatonin through an implanted SOP on the prefrontal region. The authors concluded that SOP has potential deployment for neural therapy and modulation for diseases such as Parkinson's, epilepsy and Alzheimer's disease [25,26].

5.2. AI technology in the heart of patient care

Artificial intelligence (AI) continues to drive advancements in patient care, more recently playing an increasingly prominent role in AI assisted cardiovascular disease (CVD) diagnoses. Researchers from the University of Texas (UT) San Antonio and UT Health San Antonio are using AI to identify the specific composition of coronary heart disease to predict heart attacks. This technology uses optical coherence tomography (OCT) to capture detailed images of a patient's coronary arteries enabling them to see factors such as plaque build-up. However, the complexity of the data generated has led to researchers developing AI algorithms to aid in interpreting OCT much faster and more reliably to improve patient decisions [27].

Additionally, the American Heart Association has granted $750,000 USD to the University of Louisville to innovate AI models to manage acute kidney injury in heart surgery patients. The project is twofold: first, to predict real time the risk of developing acute kidney injury, and second, to establish a clinical decision support system to aid clinicians in clinical decision making [28].

Last, a research team lead by Associate Professor Joshua Lewis at Edith Cowan University in Western Australia, has developed a machine learning-algorithm to accurately assess abdominal aortic calcification (AAC) from routine bone density testing. This predictive model significantly shortens the screening time required by a trained radiologist to score AAC severity, and instead can score hundreds of images within a minute. This technology opens the scope of predictive modelling to encompass not only CVD, but fall-related hospitalizing and provide early patient education interventions [29,30].

5.3. Zosurabalpin's breakthrough mechanism targets carbapenem-resistant Acinetobacter baumannii

In the recent studies published in Nature, Zampaloni et al. and Pahil et al. report significant progress in the development of novel treatments for carbapenem-resistant Acinetobacter baumannii (CRAB) infections. They identified a unique chemical class of molecules, known as tethered macrocyclic peptides, that showed promising antibacterial activity against A. baumannii. Through optimization and refinement, they developed zosurabalpin, a drug candidate with improved solubility and safety profiles compared with existing molecules. Zosurabalpin targets a previously unknown mechanism of action by inhibiting the transport of lipopolysaccharide through a complex of proteins essential for the outer-membrane structure of Gram-negative bacteria. Furthermore, structural studies conducted by Pahil and colleagues revealed the specificity of zosurabalpin for A. baumannii, highlighting its potential as a bacterium-specific antibiotic. Laboratory tests and animal studies demonstrated the effectiveness of zosurabalpin against CRAB infections, leading to its evaluation in Phase I clinical trials. Additionally, the bacterium-specific nature of zosurabalpin suggests potential benefits for preserving the human microbiome. Overall, zosurabalpin offers promising prospects for addressing the urgent need for novel antibiotics to combat drug-resistant bacterial infections [31–34].

6. Summary

As we entered the new year, January 2024 saw the emergence of new therapies entering the market for rare and advanced stage diseases. Specifically, cell and gene therapies had a strong presence with regulators such as Swissmedic authorizing the first gene therapy for hemophilia B, while the FDA approved Amtagvi for unresectable or metastatic melanoma. Conversely, big pharma companies such as Merk and Johnson & Johnson are approaching patent expirations for large revenue raising drugs, warranting a need to reassess the company's financial structure and direction. As always, AI continues to drive improvements in patient care, with significant involvement in CVD clinical support systems recently reported.

Author contributions

All authors contributed to the design, drafting, revision and final approval of the manuscript. All authors agree to be accountable for the work presented in this manuscript.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Competing interests disclosure

HA Salami is a member of the Therapeutic Delivery Editorial Board. They were not involved in any editorial decisions related to the publication of this article. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed.