Rare disease patients’ odyssey captures more headlines, with paramount evidence on the negative impact of misdiagnosed and undiagnosed rare disease patients. A new study that was launched lately by Lewin Group illustrates that on top of all the known imperative reasons for early detection and diagnosis of patients suffering from orphan disease, a delay in diagnosis can also result in a significant monetary impact of between $86,000-$517,000 per rare disease patient. This number was retrieved through extensive work of the group monitoring over 1400 rare disease patients and caregivers in the US. The impacted sum takes into consideration both direct and indirect costs. Direct costs associated with tests, clinic visits, and medications (i.e., without travel expenses that can be significant with over 4 out-of-state health-related trips), while indirect costs consist of missed working days for caregivers and patients. The robust study consists of 7 rare diseases, impacting both children and adults, and provides a balanced overview of various rare diseases pharmacoeconomic impact of late diagnosis. The notable findings reveal the sensitivity involved in the early diagnosis of rare diseases, one bold example being babies suffering from Severe Combined Immunodeficiency (SCID), a disorder that impairs the babies’ immune deficiencies to fight infections, which can result in death in most of the cases before the year of 2. If diagnosed at birth or close to it, a bone marrow transplant can successfully treat the disorder. Additionally, the study climaxes the budget impact effect of late diagnosis compared to timely diagnosis of rare diseases, with a direct link between time lapsed and cost, both for the diagnosis procedure and treatment. Another interesting finding was the validation of the rare disease diagnostic odyssey that took on average 6.3 years – aligned with the 7 years on average previous assumptions. Another interesting validation was for the number of physicians that a rare disease passes until he’s properly diagnosed, which stands on average 10 physicians. Apart from the abovementioned study, patients suffering from rare diseases have a deterioration in the quality of life and in most cases irreversible accumulated health damage. There is an uplifting trend for biotech companies developing or distributing drugs for rare diseases to give more and more weight to rare disease patients’ journey due to the immense amount of undiagnosed or misdiagnosed patients, that reach approximately 50% of the prevalence patients pull. As the cost of treatment of rare diseases is 5.5 times higher and reaches approximately $125,000 per patient per year, there is a strong economic logic behind the companies’ enthusiasm to invest more in this space. Some of the methods involved in these activities were merely available 3 years ago, as the ChatGPT and the pandemic lockdown and the use of AI and ML were accelerated beyond any previous estimation. Today a rare disease company can map the patient journey and perform reverse engineering of the patient imperative specialist, and by that identify the most critical points for future interactions. In Pompe Disease for example it will be imperative to work closely with pediatric neurologists, by establishing a data-sharing collaboration that will allow the orphan drug companies to develop algorithms based on the patient’s historical health data, family heritage, patients’ conditions, medications, and other health manifestations, to outline the most prominent candidates to be allocated for the future rare disease evaluation. Arphio’s data science team performs a systematic automated literature review powered by a unique NLP algorithm to better capture the disease phenotype, manifestation, and associated diseases, physicians, and drugs, for better identification of the patterns leading to the rare disease. Additionally, Arphio uses a sophisticated detection and diagnostic identification tool, to propose the best possible instrument to detect the disease in a timely and accurate manner. All those out-of-the-box solutions are thanks to the technological advancement that allows us to harness computer technologies and power to mimic human experts at scale. A close collaboration with patients’ organizations is imperative to shorten the rare disease patient odyssey. As rare disease advocacy groups hold valuable data and patient communication, that could be of great use by technologically oriented rare disease companies. Additionally, rare disease advocacy groups are a great broadcast channel for creating more awareness among various stakeholders and promoting various initiatives involved in the detection and improvement of patients suffering from rare diseases. Having access to data from Real-World-Evidence (RWE) is essential, as it can illuminate various patterns through the application of Machine Learning (ML) and Artificial Intelligence (AI), to better identify hidden patterns within the data. This valuable information could be the cornerstone for future evaluation, and the shape of detection and diagnostic algorithm calibration. Healthcare professionals are the classical holy grail of rare disease patient identification, and their collaboration is essential to shorten the rare disease odyssey journey. Nevertheless, this stakeholder population needs to be addressed with caution and respect, as they are often reluctant to new technological ideas, that weren’t supported by proper clinical trials. Hence, it will be essential to harness them sooner rather than later in the endeavor of shortening rare disease patients’ diagnostic journey. Engaging with payers earlier in the process is essential, as they might come up with a specific request that could be calibrated, while the company performs the rare disease patient identification. For example, specific age categories, disease stages, and patient conditions could all be part of the algorithm calibration to allow fast and early diagnosis and treatment. While all rare disease patients should get access to treatment, it is inevitable to acknowledge that the payer could not cover all the rare disease patient population due to budget restrictions. Nevertheless, an orphan drug company could be sound to the payer feedback and cope with the un-servable patient pull in various creative ways. Last but not least a rare disease company needs to work on the awareness of the disease they represent, to create a higher patient and caregiver engagement that will allow more data collection and proactive engagement with the company’s diagnostic activities. As an example, a company can create a direct campaign, highlighting the manifestation of various rare disease symptoms among a predefined population and advising them to go see their doctors if the patients suffer from those conditions. Additionally, creating awareness of heritage disease checkups by various family members could ignite a proactive engagement that will help in rare disease patient identification. The world has advanced a lot and orphan drug companies need to see beyond the classical patient journey and understand the importance of shortening the patients’ odyssey for the benefit of first of all patients and all the stakeholders involved. We learned from the latest Lewin Group trials that payers should be sounder, towards the negative impact of late diagnosis of a rare disease and encourage companies to earlier rare disease patients’ identifications. I see a bright future for rare disease patient outcomes and am bullish on the impact the technological revolution has brought into this space. I strongly encourage orphan drug companies to collaborate with technological champions in the detection and diagnostic space to accomplish their mission in a faster and more prominent manner. “Rare but not alone” have to be exercise to the maximum extent possible.