By employing DNA-based technologies, EstBB can identify mutations that put you at increased risk of specific diseases and customize medication dosages accordingly. EstBB also keeps tabs on an extensive array of personalized medicines in development – such as gene therapies, pharmacogenomics, and cell therapy treatments.
However, manufacturing, regulatory, reimbursement, and pricing challenges still need to be overcome for genomic medicine to reach its full potential.
Wave 1: Gene Therapy
In 1990, Ashanthi DeSilva underwent the inaugural gene therapy trial. The goal was to cure her of severe combined immunodeficiency – an inherited condition in which her immune system could not recognize and fight off infections that would otherwise kill her – with replacement of an enzyme (ADA) with one from a viral vector and subsequent injection into blood cells. Ashanthi went on to live a normal life free from infections that once plagued her.
Today’s most advanced gene therapies employ CRISPR/Cas9 genetic scissors to cut or replace disease-causing genes in living cells for treatment or even cure of certain illnesses. These treatments are generally known as cell and gene therapy (CGT) and represent an entirely new class of medicines that may provide cures without the side effects associated with small-molecule medicines.
Gene therapies offer immense promise but can be challenging to implement successfully. Not only is an understanding of genetics required, but gene therapies must also include clever delivery systems capable of hiding from immune systems while effectively targeting target cells with therapeutic DNA delivery without creating collateral damage to healthy tissue. They must also meet high levels of molecular precision, editing efficiency and manufacturing scale to be truly successful.
Therefore, most approved gene therapy treatments focus on rare diseases. Rare diseases tend to have clear genomic targets with high unmet needs that go largely unfilled by other therapeutic modalities like monoclonal antibodies.
Treatments that meet this standard will likely gain the attention of insurers and patients – provided they can be packaged into an affordable yet simple cost-cutting package. Beyond payers, additional stakeholders such as pharmaceutical companies and physicians must come together behind these new medications to support them.
As genomic medicine begins to gain steam, it is worth keeping in mind that it remains relatively young and will present significant challenges in its early years. These may include managing its complexity – which requires an entirely different talent pool than traditional drug R&D processes – as well as finding ways of working more effectively than before.
Wave 2: Gene Editing
Biochemical tools, such as CRISPR-Cas9, allow scientists to change the DNA sequence of living organisms with ease and precision. Their release has created tremendous excitement due to their potential to expand biological understanding, alter microbe and plant genomes, treat diseases in humans and other animals as well as enhance human traits – but also raise ethical concerns over whether humans might choose to alter future generations’ genes in order to treat disease or improve traits.
Summit participants noted that germline gene editing could have lasting impacts for humanity’s long-term development. This may result in shifts in human population and increased biodiversity; hybridisation processes that produce offspring with more complex genetics or distinct features than their parents could also take place and this would likely have profound social and economic ramifications.
Urnov and Rudolf Jaenisch from Massachusetts Institute of Technology have both noted the feasibility of somatic cell gene editing as a means of treating disease or improving human traits, not germline gene editing. Under this approach, cells could be modified so they produce beneficial proteins or replace damaged ones without altering their parental origin; such cells are found in blood and liver tissue and could even be transplanted into patients to cure illness or enhance traits.
Participants at the summit discussed both ex vivo and in vivo gene editing as a potential therapy method. Ex vivo editing involves isolating cells from patients and editing them separately before reinjecting back into their bodies for therapeutic effects. At present, ease of delivery to targeted organs or tissues is critical to gene therapy products being successful.
Some attendees advocated for an ongoing international forum to address clinical gene editing, providing informed decisions by policymakers, regulators, research funders, patients and their families, healthcare providers, faith leaders, public interest advocates and industry representatives. Such forums should involve diverse disciplines including biomedical researchers, social scientists scholars ethicists as well as members of the general public.
Wave 3: Personalized Medicine
Personalized medicine involves tailoring medical care to each patient based on his or her genetic makeup, whether that means blood testing to detect BRCA mutations associated with increased risks for breast and ovarian cancer, or conducting more comprehensive genomic sequencing processes to identify those at increased risk of disease development. More and more, personalized approaches are becoming part of routine healthcare through gene-based diagnostics and targeted therapy approaches for certain disorders.
Though recent gene therapy approvals for inherited disease has generated much excitement, personalized medicine’s promise goes well beyond simply treating specific genetic variants. Furthermore, low-cost DNA sequencing makes genomic information available for preventive healthcare purposes.
Pre-implantation testing to avoid genetic disease, carrier screenings to identify those at risk for diseases (like hemophilia), and medicines tailored for people with specific genetic profiles such as aspirin’s new formulation that reduces cardiovascular risk in those carrying certain genetic variants will all be part of this trend. Soon pharmacogenomics tests may become widespread to help predict how patients will respond to drugs or inform dosage selection decisions.
Biomarker development and application represent one of the greatest obstacles to realizing the promise of personalized medicine. A biomarker is defined as any characteristic which detects, diagnoses or monitors drug effects; such characteristics could include normal biological processes as well as pathogenic ones. Classic biomarkers include blood and urine parameters, radiology scans/MRIs/imaging data. Recently however, biotechnology companies have started looking into genomics as a source for novel biomarkers that measure expression/activity/regulation of genes. These will be used to develop targeted therapy aimed at controlling the activity of disease-associated genes. As this next wave of personalized medicine advances, its shift away from treating symptoms towards prevention may accelerate and lower health care costs rapidly – prompting leading innovators to reevaluate their R&D, business, and clinical models to capture personalized medicines’ worth within healthcare services.
Wave 4: Targeted Therapies
Targeted therapies hold enormous promise for treating certain rare diseases. These medicines work by binding to and inhibiting specific proteins, thus slowing disease progression while decreasing side effects; gene therapy and immunotherapy are two examples of such highly targeted medicines.
Targeted therapies stand apart from previous waves by directly treating specific mutations rather than managing symptoms over time. Targeted therapies could transform healthcare by offering one-and-done solutions rather than managing symptoms for life.
However, their high cost can be a barrier for patients. Some high-profile gene therapies costing upwards of $1 million are sometimes not covered by insurance; but it’s good news that innovative therapies exist and continue to emerge on the market.
Genomic medicines span an impressive 1,200 active clinical trials, with gene therapies and regulatory oligonucleotides showing particular promise in these fields. A handful of therapeutics utilizing gene editing technologies – like Luxturna for genetic eye disorder treatment or Zolgensma for spinal muscular atrophy treatment – have already reached commercialization; among these treatments are monogenic disorders treatments like Luxturna for an eye disorder and Zolgensma for spinal muscular atrophy as well as cancer drugs made available through commercialization such as Luxturna or Zolgensma for their respective uses as well as cancer drugs developed through genome editing technologies.
It is extremely exciting that genomic medicine is becoming an emerging frontier of healthcare, and I look forward to the challenges it will present us over time. Over the next decade we will see an exponentially higher number of cures for genetic diseases than we ever saw before – however there will still be regulatory hurdles, manufacturing requirements, and pricing concerns to contend with.
As such, the IGI is taking this challenge head on and has established a task force dedicated to accessing these innovative therapies. Their team will draw upon expertise of IGI members with backgrounds in drug development, intellectual property licensing, organization funding models and pricing/access strategies in order to formulate strategies that address these issues and allow genomic medicines to reach more patients, thus driving transformational change within healthcare.
