Identifying the Needs
Step one in wave genetics enrollment is to assess the needs of potential participants. This can be accomplished via surveys or focus groups; understanding potential participant needs allows researchers to create targeted outreach campaigns designed to increase participation. Likewise, it’s crucial that researchers identify any barriers to enrollment as early as possible so that strategies may be devised to overcome them.
Utilizing these techniques can significantly boost the success of WGS programs and increase recruitment rates. For instance, BabySeq Project’s research demonstrated that enrollment rates increased with proactive outreach from health care providers; furthermore Geisinger Health System’s research demonstrated mail-based outreach as being both cost-efficient and effective, making this method applicable across hospitals for reaching underrepresented populations.
AFTD commends Wave Life Sciences and GSK on their efforts to enroll patients in this trial. Both companies share our goal of creating innovative therapies that improve people’s lives; as part of this discovery collaboration, GSK receives an exclusive global license to Wave’s preclinical oligonucleotide program for alpha-1 antitrypsin deficiency (AATD), WVE-006, which represents a first-in-class RNA editing therapeutic therapy solution.
Developing a Strategy
Researchers seeking to create an enrollment strategy for wave genetics must understand what motivates individuals to join genetic research studies. With this understanding in place, enrollment methods and strategies can be enhanced; for instance it is important to determine how many individuals are interested in genetic screening programs and attendance of an enrollment session with a genetic counselor, as well as whether participants would like to join studies that examine specific genetic conditions.
Proactive population screening could transform genetic research and healthcare in the future, becoming more common as government funding grows and programs designed to integrate genomics into healthcare enroll participants (All of Us Research Program Investigators 2019; Tripp et al 2021). It is crucial, however, to assess how many individuals are willing to undergo genetic testing for the first time as well as any barriers which prevent participation.
One approach for tackling this problem is taking a targeted approach that identifies individuals who carry the highest genetic risks for disease and inviting them to participate in clinical trials. This method has proven cost-effective while relieving pressure from health care systems – Wave Genetics has used this strategy successfully by enrolling over 28,000 individuals for its genome sequencing and personalized medicine programs (Wave, 2017).
Wave Genetics‘ platform facilitates easy access to genetic resources for research studies. Scientists can leverage this enabling platform for large scale genomic analyses that identify potential drug candidates.
Wave Life Sciences was established in 2012, and since then has attracted significant pharmaceutical companies and investors, such as Pfizer and Takeda Pharmaceuticals as partners. Unfortunately, however, Wave has experienced multiple setbacks in its development of new treatments for HD and FTD – its experimental drug WVE-004 failed the FOCUS-C9 basket trial for cases associated with mutations of C9orf72 gene.
Implementing a Strategy
An integral component of genetics research is attracting patient participation to studies. Unfortunately, existing research remains inconclusive on how best to approach proactive population-level genomic screening by hospital systems; moreover there may be different preferences among demographic groups when it comes to outreach methods. One study discovered that mailing paper brochures resulted in higher enrollment rates than face-to-face interactions, though this approach incurs considerable costs and may not be viable in communities lacking hospitals; other research indicates digital outreach such as email or text results in higher enrollment rates as well.
On another approach to enrolling people into genomics studies is using EHR-linked biobanks to identify participants who might carry rare variants associated with specific phenotypes. This technique, known as population genomic sequencing (PGS), has proven itself successful in various trials but may be too costly and ineffective on a national scale without significant government support. Finland stands out as an exception where PGS could potentially become cost-effective by linking GWAS data directly to EHRs and clinical records as part of a large scale population-based study called FinnGen.
Wave has developed ASOs that work by interfering with genetic messages telling cells in our body to produce specific protein molecules. In particular, Wave’s ASOs used in the FOCUS-C9 trial were designed to decrease levels of harmful huntingtin while leaving healthy levels unaltered – unlike approaches being tested by Roche and UniQure which aim to lower both forms.
Wave Life Sciences should be applauded for their dedication to sharing the results of the FOCUS-C9 trial with all researchers, which will allow scientists to learn from this groundbreaking basket trial. Although Wave recently shelved two drugs targeting Duchenne muscular dystrophy and Huntington’s disease due to disappointing research setbacks, we believe it’s imperative for them to keep pushing genetic medicine forward by innovating new approaches and pushing boundaries forward.
This press release includes forward-looking statements as defined by the Private Securities Litigation Reform Act of 1995 and subsequent amendments. These statements outline our expectations regarding a collaboration and licensing agreement, the discovery, development, manufacturing and commercialization of potential oligonucleotide therapeutics. Forward-looking statements in this document are based on current plans and assumptions and involve risks and uncertainties that could cause actual results to differ materially from what was planned or expected, including the risk that Wave will not reach an agreement regarding research, development and commercialization of potential oligonucleotide therapies. For more information about these and other risks and uncertainties please see its filings with the Securities and Exchange Commission.
Monitoring a Strategy
Wave Life Sciences has formed partnerships with major pharmaceutical companies like Pfizer, Takeda Pharmaceutical and now GSK. It has raised $102 million from public investors, as well as garnering support from major medical organizations and major investors. Unfortunately, however, Wave has also encountered several setbacks; its experimental drugs for Duchenne muscular dystrophy and Huntington’s disease failed early stage trials and ultimately went nowhere.
Wave is currently conducting a Phase 1b/2a clinical trial of its WVE-003 treatment for HD. This involves administering small molecules known as oligonucleotides to lower levels of the harmful form of huntingtin produced by cells; they’re then injected directly into the brain for effective delivery – unlike previous huntingtin-lowering approaches from Roche and uniQure, Wave’s oligonucleotides will only reduce harmful forms while leaving healthy versions unchanged.
The WVE-003 study will assess if administering oligonucleotides into the brain using this technique improves symptoms associated with HD, as well as whether this treatment impacts progression over time.
To ensure participants receive the appropriate medication, all participants must undergo testing for a single nucleotide polymorphism (SNP), required as part of participation in this trial. Results of this test will determine eligibility for treatment with WVE-003.
As MVP patients age and genetic diseases increase, so too does their need for effective therapies and monitoring of health outcomes from them. Access to longitudinal data sets such as those provided by VA, Kaiser Permanente and UK Biobank provides this vital service. To meet this demand for genomic research.
Success for these initiatives lies in recruiting and retaining a large, diverse pool of volunteers. Studies have demonstrated that enrollment rates can be dramatically increased with proactive outreach by healthcare providers; one example being the BabySeq Project where mail-based outreach to families led to initial conversations with healthcare providers as well as follow up meetings with genetic counselors significantly increased enrollment to WGS programs.
