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EF: If health had its own COP26 and you were a speaker, what would be your message to world leaders?

NL: My message would be to bring the patients back to treatment. Covid significantly damaged the doctor-patient interaction, mainly impacting chronic diseases patients. Healthcare is not only about Covid; new diseases could break out and impact health and health resources, and we must be prepared. With all the resources directed to Covid, diseases such as diabetes, rare diseases, oncology, immunology and other chronic ailments have been pushed back. There will be a price to pay for the delay and neglect of disease management.  Before it is too late, we must turn our attention back to diagnostics and face the new wave of diseases that will surely come. 

EF: What were the lessons learnt from the process of managing through a pandemic? 

NL: Health must go on; even with a pandemic around us and the challenges on many fronts, we never stopped diagnosing and serving rare disease patients. Our medical and market access departments navigated the Mexican healthcare system, got treatments to our patients, and communicated with physicians without overloading them with new formats at a time of crisis. Our biggest learning was we continued to operate by adapting and being flexible, not in the timelines we would have liked, but we nevertheless met our objectives. Through 2021 we established the building blocks to work with the government and treat patients in the public sector and the community in general. Despite challenges, we have advanced and achieved our commitments. 

EF: How can we restore awareness of rare diseases in the Mexican market?

NL: Innovative treatments and therapies are essential, and there must be a clear objective while navigating the environment. We focus on the patient's story, providing what they lack. With a high-quality product and life-changing therapies, the story tells itself. We are bringing innovation to serve an unmet medical need, and we are gaining credibility with the government and health authorities. It has been hard to get decision-makers to sit down with us as they are more worried about getting vaccines, finding more beds or covering many other decision areas, but it is all part of our job. We must find solutions for the communities that haven't had access to any treatment whatsoever, so we work with the government to give access to Mexicans bringing innovative products to the market. Despite the challenges,  in 2021 we have met some of our critical milestones; in October, our first therapy was approved by the Consejo de Salubridad General, coming within the year of the COFEPRIS approval. It was a record-breaking occurrence and a positive message from the government on prioritizing rare diseases and innovative therapies that bring value to the patients, the community and the country. We also submitted a second therapy for incorporation in Compendio Nacional de Insumos para Salud and a third treatment was submitted for Orphan Drug Designation to Cofepris, showing good traction in bringing innovative treatments for Rare Diseases to Mexico. 

EF: Have you identified and introduced any new KPIs during the pandemic?  

NL: Our financial KPIs are a good metric of how we are doing, but it is hard to forecast as a startup because any slight delay causes the needle to move. We work on diagnostics for rare diseases in Mexico, supporting physicians with genetic/molecular diagnostics. We started by diagnosing the first wave of undermanaged patients, all well-identified by the physicians. Then, patients came in after hearing about our programs and diagnostics. When the pandemic broke out, we hit a plateau, and then numbers started decreasing on a month by month patient average for diagnosis. From an upward trend before the pandemic, we now have a downward trend in patient diagnostics. This can be read two ways: i) Pandemic effect in interaction with HCPs. It is easy to build on relationships that existed pre-Covid and transition to virtual, but when a relationship does not exist, it is tough to establish a  scientific relationship from scratch and remotely. We worked with physicians we already knew, but we had difficulties growing that baseline and engaging new physicians on patient diagnostics, which affected the KPIs. ii) Patients started postponing their appointments as they saw more danger in getting Covid than not seeing a doctor. Patients delaying appointments became a second trend; paediatricians were concerned about pediatric patients avoiding hospitals. Vaccines were delayed, many kids had anxiety, put on weight, all a reflection of not going to the doctor. The KPIs have reflected this impact in the rare disease community, and the challenge of engaging with physicians in a virtual world makes everything more complicated. Connecting initially on a personal level improves engagement, and it is that much harder without that initial connection.

EF: 5% of the health budget makes 70% of health decisions; early diagnostics are the backbone of rare diseases allowing for correct and precise decisions. ¿How can we keep momentum on the importance of early diagnostics? 

NL: When treating diabetes, big pharma concentrates on treatment and diagnostics organically, as it is in the healthcare professional's formation. Rare disease companies work on the patient and the disease end to end; it is our DNA to bring solutions. Part of the integral services rare disease companies provide is walking with the patient from when they are diagnosed and through their treatment. We understand it is hard to have a large genetic testing panel in a public hospital and within the public system. The cost has lowered over the years, but it is still an expensive investment for a small number of patients. We absorb the cost and provide services to physicians free of charge as we invest in programs and diagnostic labs to provide testing and differential diagnostics, making a massive difference in the treatments for the patients. They get the precise treatment they need after having the right diagnosis, and there is no waste of money in experimental treatments or spending two or three hundred thousand dollars in treatments without the proper diagnosis. Our services include diagnosing patients with genetic confirmation, and we have treatments for specific mutations. We are also monitoring legislative changes in newborn screening, which is seen as a political, medical and ethical dilemma, and we are encouraging the authorities to analyze and find the right balance of diseases that need to be addressed early on. Newborn screening diagnostics could be a game-changer; decisions can be made having a diagnosis the first day or first month of a baby's life and can be immediately treated if necessary. This discussion is still ongoing, and patient associations have been working to incorporate more diseases. There is a lot we can do to accelerate early diagnosis and close the gap: 

1) Newborn screening, 

2) Artificial intelligence and electronic medical records: including algorithm programs with variables and warnings for physicians, for example, four specific combined variables point to a certain disease. We can use technology for early diagnostics, although Latin America still lacks conditions to do this.  

3) High-risk population screening: Fabry disease, for example, mainly affects kidneys; there are a lot of patients in dialysis without a diagnosis who could have Fabry disease. If we screened dialysis patients, we would find a segmented population with Fabry disease. This is just an example of how screening high-risk populations can lead to an accurate diagnosis. 

Early diagnostics and generic testing tools provided by companies, the government or academia is the proper way to close the gap in diagnostics. The devices have evolved, and rare disease testing costs have dropped considerably with hundreds of genes already tested. The cost drops, availability improves and impacts diagnosis.

EF: How can we increase focus and value on rare diseases for future healthcare budgeting in the government's resource allocations? 

NL: That is a million-dollar question. The budget is limited, and it isn't easy to know where to place resources, something like having a blanket that won't entirely cover a person when you try to cover your head, then your feet get uncovered and vice versa. The relatively small number of rare diseases patients doesn't significantly impact the healthcare budget system, but the issue lies in that an individual patient uses many resources. Diego Roselli, a health economist from Colombia, wrote a paper on rare diseases, comparing rare diseases to the situation of the thirty-three Chilean miners that survived 70 days trapped 700 meters underground. The cost to get them out was over a million dollars per person, and there was no doubt in investing the money to save them. On the other hand, a Gaucher patient costs around 200 hundred thousand dollars in therapies, but it is considered too high to pay. Because the focus was on those thirty-three lives, there was no price tag. A good message to bring to payers and the government is to focus on rare disease patients born with mutations, who should indeed have the opportunity to receive treatment to live an ordinary life. Limiting treatments for rare disease patients is part of the system's inefficiencies; Brazil has solved this issue through central negotiations with the Ministry of Health. Mexico could do the same, looking for opportunities at the industry as an ally to achieve a win-win for everybody: patients, industry and government. Value can be gained with all the stakeholders sitting down and collectively finding solutions for the best disease management. There are many actors prepared to bring value to the operation. The Covid vaccine is a case where this has been successful, with all parts collaborating towards a goal. The micro-economy of rare diseases is very complex, especially at the bottom of the pyramid. Families with children with rare diseases have many difficulties, without access to evolution in the rare disease, no medication, and very few options to move on and improve. Sadly, this is a widespread occurrence in Latam, the highest impact of rare diseases always happens in the lower economic sector. 

EF: What are your expectations for Mexico?

NL: Ultragenyx is focused on bringing the next generation of medicines to the world, but there are challenges as Mexico doesn't yet have a regulatory framework to bring these therapies to the market. 

  1. We are taking the first steps to bring innovative or next-generation therapies to the region and looking into opening sites for phase three studies as Latam is rich in genetic diseases which go hand in hand with poverty, communities with high endogamous relationships and isolated communities. All this offers exciting opportunities to bring sizable R&D to the region. We are working with authorities to put the framework together, which means working with physicians and medical scientists who understand the power of gene therapy and its potential challenges.
  2. We are collaborating with other companies interested in the same topics, such as BioMarin and PTC through collaborative efforts in AMIIF to bring proposals to the table
  3. We are potentially ready to cure some diseases – today, payers pay perpetually to control chronic diseases, but we can potentially convert a chronic disease patient to an acute patient in one or two treatment sessions at a 90% success rate as some studies of gene therapies are showing. We are analyzing how the patient and payer will receive this breakthrough and if they will be willing to pay for market access in innovation in payer models. All this must be done before the therapies come to market, but we are confident there will be space for our products because there are gaps in the system.

There is an initial analysis that around 40% of the R&D industry in the next decade will come from Rare diseases or next-generation therapies (gene therapies, cell therapies, etc). It is a ship everybody wants to be on because it's where the innovation will be in the next ten years. 

EF: When you look back on this period in your professional career as a leader, how would you like your tenure to be remembered?

NL: For the resilience shown and for having made things happen with the environment against us. If we managed to do what we did during a pandemic, we could do anything. Ultragenyx is a startup, so we did much hiring with all the virtual complexity involved in getting people on board remotely. We have had to put an additional effort into communications, touching base with the teams weekly to work toward the right objectives, so having the right people was essential. Having a purpose was essential and a huge lesson learnt. I am happy to say everybody has come through. We are closing 2021 with major achievements in processes and we have moved forward with authorities in Mexico, all done while battling a pandemic. Just imagine what we can do without Covid on the horizon!

November 2021