Year in review: EPR’s top stories of 2023

At the beginning of this year, EPR reported on the potential blockbuster pharmaceutical drugs to watch in 2023.

Since then, EPR has covered developments for several of the therapies highlighted in the report. This includes the National Institute for Health and Care Excellence (NICE)’s recommendation of the first treatment for Parkinson’s disease, Produodopa (foslevodopa–foscarbidopa).

Additionally, in October, EPR shared Phase III trial data for the type 1 diabetes treatment TZIELD (Teplizumab), which suggested that the medicine could slow disease progression.

The year 2023 also brought much advancement in the Alzheimer’s space for the pharmaceutical industry. For example, due to prevalence of the disease across the globe, US approval of the biologic lecanemab was particularly anticipated by both the industry and patients.

Following Clarivate’s report indicating a predicted trend of biologics approvals, in April, the European Medicine Agency’s (EMA) human medicines committee granted a positive opinion for biologic Cosentyx^®, making it potentially the first new treatment for hidradenitis suppurativa patients in a decade.

Another treatment modality that has witnessed significant advancement this year in the pharmaceutical industry, is cell and gene therapy. Dr John Maher, Chief Scientific Officer of Leucid Bio shared with EPR that this year, “we have witnessed tremendous advances in CAR T-cell immunotherapy of solid tumours.”

Dr Maher elaborated on data from a clinical trial of GD2-specific CAR T-cells in children with relapsed refractory neuroblastoma. The findings were published in the NEMJ in April 2023 and demonstrated “the best solid tumour CAR-T data reported to date – and by a country mile! With 33 percent complete remission and 30 percent partial remission, I am excited and encouraged that we are finally witnessing the dawn of effective CAR-T solutions for patients with solid tumours.”

EPR’s top stories in 2023

Clinical development

DMT

The first major study on N,N-Dimethyltryptamine (DMT) covered by EPR at the beginning of 2023 was only one set of data released throughout the year that established the potential of psychedelics in treating mental health conditions.

In this Phase IIa trial, the remission rate for participants with major depressive disorder (MDD) was a remarkable 57 percent at three months following a single dose.

“SPL026 (intravenous DMT) with supportive therapy was shown to have a significant antidepressant effect that was rapid and durable,” Dr Carol Routledge, Chief Medical and Scientific Officer at UK biotech Small Pharma commented when the results were announced.

The researchers stated that DMT could provide a superior alternative to other psychedelics, such as psilocybin and LSD, which require lengthy treatment sessions. This is particularly the case for patients who experience little benefit from existing antidepressants, Dr David Erritzoe Clinical Psychiatrist at Imperial College London and Chief Investigator of the Phase I/IIa study noted on the results.

Cell and gene therapies

Gene therapy for spinal muscular atrophy (SMA)

On 16 March 2023, NICE recommended gene therapy Zolgensma^® (onasemnogene abeparvovec) for certain patients with presymptomatic spinal muscular atrophy (SMA).

As a treatment designed to help halt disease progression before symptom onset, “Zolgensma will be the first treatment to be routinely commissioned for presymptomatic babies in England,” Imran Kausar, General Manager at Novartis Gene Therapies UK explained.

Several days later, Novartis released data from its 15-year long-term follow-up study of onasemnogene abeparvovec.

Interim results from the LT-002 study found that all patients (100 percent) maintained motor milestones that were achieved during their respective parent studies in the follow-up period”

The findings showed that some patients from the long-term follow up studies were able to “maintain and, in some cases, gain motor milestones when they are nearly eight years old [and this] is truly transformational,” shared Dr Jerry Mendell of Nationwide Children’s Hospital in the US.

Kite’s CAR T-cell therapy

Also in March, Kite announced primary overall survival analysis results from its Phase III ZUMA-7 study of Yescarta^®. Data showed a 2.5-fold increase in the patients with lymphoma who were alive at two years post-study and did not experience cancer progression or require further cancer treatment compared to standard of care (SOC).

The CD19-directed genetically modified autologous T cell immunotherapy is therefore the first treatment in nearly 30 years to demonstrate statistically significant improvement in overall survival for initial treatment of relapsed/refractory large B-cell lymphoma (R/R LBCL) versus SOC.

ZUMA-7 is the first and largest Phase III study of any CAR T-cell therapy, with the longest follow-up.

Pharmaceutical manufacturing

Oligonucleotides

Last month, the Centre for Process Innovation (CPI) announced a new Scotland-based manufacturing facility focusing on oligonucleotide therapeutics. On social media, CPI declared that £20 million will fund construction and kit-out of the facility.

Since current capacity for manufacturing oligonucleotides “is insufficient”, CPI noted that its new Oligonucleotide Manufacturing Innovation Centre of Excellence will support demand and help to drive innovation for these medicines.

The new facility will put Scotland “at the heart of advanced medicine manufacturing techniques,” Dave Tudor, Director of Pharmaceuticals at CPI stated in the original announcement.

According to CPI, the facility is set to be completed in late 2025.

Key developments in pharmaceutical manufacturing – September 2023

So far in 2023, AbbVie has proved itself as a substantial player within the acquisitions space. Less than a week apart in November and December, the company revealed that it intended to make two multi-billion-dollar acquisitions.

The first, was AbbVie’s intended $10 billion oncology acquisition. Then this month, the company declared that it planned to acquire neuroscience specialist Cerevel Therapeutics for $8.7 billion.

Pharmaceutical regulation

EU Annex 1 revision

A major shift in the pharmaceutical industry this year was undoubtedly implementation of the much-anticipated revised EU Annex 1 – Manufacture of Sterile Medicinal Products, on 25 August 2023. This regulation saw pharmaceutical manufacturers being required to apply the good manufacturing practice (GMP) regulation into cleaning and bio-decontamination procedures of sterile products.

First oral advanced therapy for Crohn’s disease approved

In February, the Medicines and Healthcare products Regulatory Agency (MHRA) approved the first oral advanced therapy in the world for adults with moderately to severely active Crohn’s disease (CD).

This authorisation of RINVOQ^® (upadacitinib) is significant because up until the MHRA’s approval, there have been “limited new treatment options approved for Crohn’s disease in recent years and many people struggle to stay in remission,” Professor James Lindsay, Consultant Gastroenterologist at the Royal London Hospital Barts Health NHS Trust explained.

First redosable gene therapy approved

In May, the US Food and Drug Administration (FDA) approved VYJUVEK™ (beremagene geperpavec-svdt) as the first-ever redosable gene therapy for both recessive and dominant forms of the rare skin disease dystrophic epidermolysis bullosa (DEB).

Data from the Phase III trial on which the approval was partly based, showed that patients achieved complete wound healing at six months and complete wound healing at three months. Chairman and Chief Executive Officer of Krystal Biotech, Krish Krishnan, stated that based on these findings, FDA’s approval “ushers in a whole new paradigm to treat genetic diseases”.

Environmental monitoring

Contamination control in cleanrooms

In March, pharmaceutical microbiology expert Tim Sandle published a video discussing fungal contamination control in manufacturing and the associated challenges within the cleanroom environment.

Usually if fungi is found in a cleanroom, this indicates a wider and often more serious control breakdown than the presence of bacteria, Sandle noted.

In the video, Sandle identified several sources of fungi contamination. For example, air handling systems are especially vulnerable, Sandle shared. “Once inside the cleanroom, the possibility of fungal survival arises due to increases in ambient temperatures and under conditions of higher humidity.”

Since the potential sources of fungi contamination are so varied, “it is imperative to consider all factors that can contribute to mould issues, as part of an effective contamination control strategy (CSS), as signalled in the revision to Annex 1,” Sandle observed.

Remedial “action will only be effective where the root cause has been determined,” Sandle concluded.

Quality standards

Nitrosamine impurities

Subsequent to the European Pharmacopoeia (Ph. Eur.)’s revision of two major general monographs: Substances for pharmaceutical use (2034) and Pharmaceutical preparations (2619) in January 2023, June saw European Pharmacopoeia Commission (EPC) members deciding to review the original strategy for N-nitrosamine control in individual monographs on active substances and medicinal products.

In the EPC’s 176th session, members recommended the removal of the Production section covering N-nitrosamine impurities from individual monographs on active substances. The EPC also suggested not including these statements in future new monographs.

In July, EMA updated its guidance on nitrosamine impurities. The regulatory body amended Q&A 10 to include elements such as the Carcinogenic Potency Categorization Approach (CPCA) and the enhanced Ames test (EAT) for establishing acceptable intakes (AIs) for N-nitrosamines.

Cannabis-based therapeutics

In August, the Danish Medicines Agency (Lægemiddelstyrelsen) the European Pharmacopoeia Commission (EPC) adopted a new Cannabis flower monograph.

The new European monograph (Cannabis flower, monograph 3028) describes the quality requirements for this raw material. Monograph 3028 will be available next month with publication of the supplement 11.5. and subsequently enter into force in Denmark in July 2024.

What will 2024 bring for the pharmaceutical industry?

In summary, with numerous significant developments in regulation, manufacturing and the clinical space observed in 2023, it is clear in 2024, alongside technology innovation, the pharmaceutical industry is primed to experience new and exciting advancements.