Over the past decade, genomic medicine has witnessed unprecedented progress. Diseases such as spinal muscular atrophy – which causes paralysis in children – now have promising gene therapies while CAR-T cell therapies have proven highly successful against cancer.
Molecular medicine’s pipeline is driven by genome editing technologies, with an emphasis on rare diseases. Penetration of this field is projected to expand over time.
New therapies for rare diseases
Though technological advancements have enabled new treatments to be developed for rare diseases, their development can be time consuming and complex. Gene therapy success relies on several factors including correct identification of genetic defect that leads to disease as well as demonstrated target organ improvement or functional restoration with enzyme replacement therapies; however, cost and availability concerns prevent widespread availability.
Due to their small patient populations and consequent lack of commercial viability, many ultra-rare conditions have not received sufficient consideration when developing therapies. However, patient-led organizations continue to explore possibilities for the clinical development of therapies targeting ultra-rare conditions.
One strategy to leverage existing genomic technologies is by taking advantage of existing platforms, which provide rapid access to the underlying pathology as well as novel therapeutic targets for drug discovery. Whole genome sequencing has enabled researchers to quickly detect many pathogenic genetic mutations leading to disease; furthermore, RNA-seq technology extends this approach by revealing metabolic pathways which may be disrupted and also proteins implicated in disease processes.
Gene and cell therapies for rare diseases have seen rapid advancement, leading to multiple approvals over recent years. While these advances are helping transform patients’ lives by altering disease progression, they also create significant cost pressures on healthcare systems worldwide.
Since the release of Glybera (Alipogene tiparvovec), its approval ten years ago stoked high hopes that virally delivered gene therapies would usher in an age of gene therapies with increased efficacy. Unfortunately, due to 30 setbacks among genomic medicine candidates during this time, expectations have been severely dimmed, leading to valuation reduction for publicly listed companies.
Targeted therapies for more common diseases
Genome-based therapies are already revolutionizing health care delivery. Pharmacogenomics allows clinicians to predict whether patients will respond favorably to certain drugs, helping reduce trial and error prescribing and hospitalizations for adverse drug reactions.
Genome-guided cancer therapy has shown promise for increasing progression-free survival while decreasing side effects, with particular success with tumor-normal matched whole genome sequencing and molecular profiling that identifies mutations driving oncogenesis to direct therapy selection. Furthermore, genomics is revolutionizing neuropharmacology by pinpointing gene variants associated with responses to certain antidepressant or antipsychotic medications3.
Genomics offers immense promise when it comes to curing previously incurable diseases. Some Mendelian disorders, including progressive blindness and lysosomal storage diseases have already been overcome using gene therapies1.1
Additionally, targeted therapies affecting larger patient populations are now within reach, with AAV vector-based gene therapies approved for hemophilia A and other rare progressive diseases. While early successes exist for other disease areas as well.
Researchers are exploring various therapeutic approaches, including mRNA vaccines, oligonucleotides and gene editing, for these broader indications. By 2024, we anticipate the convergence of diverse therapeutic modalities will offer genomic medicines exciting new opportunities. Cytiva’s viral vector production experts recently hosted a webinar where Duke University School of Medicine experts discussed multi-modality as well as shared best practices for optimizing clinical development of AAV-based gene therapies – watch its replay below or download The State of Viral Vector Manufacturing 2024 to gain more knowledge.
Manufacturing challenges
Success of pioneering gene therapy alipogene tiparvovec (Glybera) and viral-mediated cell therapies has raised expectations that genomic medicines will lead to breakthroughs in regenerative medicine. Unfortunately, one-off costs for these treatments are largely driven by meeting pharmaceutical manufacturing standards, or by “designing in manufacturability.”
Autologous cell therapies present unique challenges when creating personalized cell products tailored specifically to each patient, using fresh supplies of cells from them. To accomplish this goal, GMP-licensed facilities with backup equipment and staff must be available if a manufacturing run fails; alternatively allogeneic cells from healthy donors with similar fitness levels could provide less expensive processing solutions.
Dosing consistency among patients is another significant hurdle, due to variations in fitness level and proliferation rate between donors of genomically modified cells.
Manufacturing challenges related to genomic medicines can be significant and must be overcome for this promising area of research to make significant headway towards changing clinical practice. Yet despite these obstacles, licensed genomic medicines in rare diseases and non-rare/non-oncology indications has seen rapid advancement. As market conditions change over time, successful commercial success will depend on improvements made across numerous areas, such as manufacturing, regulation, reimbursement pricing and patient willingness. Regardless of current setbacks the industry should invest further in this promising therapeutic innovation space.
Regulation
Genomic medicines represent a game-changer in healthcare, offering hope of curing genetic conditions and treating diseases in ways never possible before. But for them to reach patients worldwide, they must first be safe and affordable – this requires making sure research costs are covered through pricing rather than subsidies – this task becomes particularly daunting when considering that some of the most promising genomic medicines target rare conditions like spinal muscular atrophy (which leads to paralysis in children) or sickle cell disease.
Genomic medicine relies on an intricate web of people and technology. This endeavor requires PCPs to adapt their practices for different patient populations and healthcare systems to provide infrastructure necessary to support it; furthermore, global regulatory oversight is also necessary alongside an adaptable innovation framework that adapts with changing scientific evidence.
Medical librarians are in an ideal position to assist the healthcare community in understanding new advancements and the ramifications for their communities. To do this, they need to remain abreast of genomic medicine’s latest innovations while being able to inform colleagues of its advantages and drawbacks.
Genomics medicines require the integration of both phenotypic and molecular data into clinical decision support systems. At PMGP of British Columbia, their customized REDCap electronic data management platform enabled smooth CGS-patient communication, standard reports with conditional logic triaging capabilities and enhanced workflow efficiencies by replacing multiple manual methods of data capture and transfer with one more efficient workflow-enhancing method.
Since the approval of Alipogene Tiparvovec ten years ago, people had high hopes that genomic medicines would accelerate into the market. Unfortunately, due to setbacks and delays in clinical trials, valuations of public genomic medicine companies have seen considerable drops.
Pricing
Genomic medicines provide a one-time solution to complicated diseases like hemophilia A (a genetic condition marked by missing or defective Factor VIII), although their per-dose prices tend to be higher than most drugs; they still cost significantly less than regular treatments such as blood transfusions or hospital stays, thanks in part to advanced manufacturing techniques like gene editing technologies which significantly lower production costs; similarly allogeneic cell therapy could improve production processes, thus decreasing costs and turnaround times.
Genomic medicine promises to revolutionize healthcare by offering more tailored and cost-efficient care, shifting emphasis from treating disease to preventing its occurrence, improving outcomes, and decreasing costs. Companies that invest in genomics as part of their business models will emerge victorious.
Low-cost sequencing technology will unlock an enormous data set that can be used to optimize diagnostic and therapeutic strategies, providing the pharmaceutical industry with an opportunity that could enhance companion diagnostics or new products significantly. But this potential must also be met with efforts that overcome potential hurdles to fully exploit this opportunity.
One of the primary challenges associated with genomics in clinical practice is ensuring that its impact is understood by medical community. Though opportunities exist, most healthcare practitioners remain unaware of how genes impact health; this knowledge gap limits genomics’ effect on patient care; however it can be closed through education and training – specifically by creating an evidence-based curriculum covering genotype-phenotype interactions.
