There are three common types of SMA. Type I cases are the most severe, historically leading to death or severe disability in 82% of babies before their second birthday. When dealing with a deadly disease like SMA, there is a strong sense of urgency.
Years earlier, Loren and Dinakar had worked their way up the corporate ladder to become successful investment bankers. This provided them the resources to support finding a treatment for Arya and others living with SMA by creating
Their first obstacle: funding. “As you know, science and drug discovery is a costly endeavor,” Loren explains. “And unfortunately, at the time, federal and private funding was shockingly low given how prevalent and high impact SMA is.”
Within three years, the SMAF turned the numbers around. They hired lobbyists, engaged politicians, raised awareness and garnered doctor and scientist support to call for funding from the NIH. The result? The NIH increased SMA funding from $3m to $15m by 2006 and publicly funded research money went from $6.5m to $30m.
Even with financial backing and increased disease awareness, by 2005, there was still little progress toward an effective treatment. By then, Arya was wheelchair-bound with a heartbreaking list of additional pulmonary, muscular and skeletal conditions. The SMAF then decided to seek partnership with innovative companies to expedite the drug discovery process.
Their search led them to PTC Therapeutics (PTC). As a leader in rare disease research, PTC understood the challenge and the potential for helping critically ill patients. United by one commitment, PTC and the SMAF joined forces in the pursuit of a treatment for this complex disease.
SMA is caused by reduced functional SMN protein levels, leading to dysfunction and death of motor neurons. Going beyond what people thought was possible, PTC created a groundbreaking platform for modifying mRNA splicing with small molecules and also discovered several novel classes of molecules that increased SMN protein levels.
This remarkable activity was clearly demonstrated in cells isolated from SMA patients, which translated into increased survival and motor function in pre-clinical models of severe SMA. The potential to address the tremendous unmet need in SMA, along with the scientific breakthrough made by PTC and the SMAF, sparked interest at Roche.
Having worked with Roche in the past, PTC knew that both teams shared a common passion and purpose to help patients with a high unmet need. In November 2011, Roche entered into the collaboration alongside the SMAF and PTC, with the goal of delivering PTC’s cutting-edge technology into a life-saving treatment for SMA patients.
“We looked forward to working with our partners, the SMAF and PTC, and using the R&D skills within Roche to deliver an important treatment option for patients,” says Christoph Sarry, Global Alliance Director, Roche Pharma Partnering. “Building on our history of developing some of the biggest breakthroughs in science, our experts were eager to collaborate on PTC’s incredible innovation.”
Using the platform developed by PTC, the Roche team, including Hasane Ratni, Medicinal Chemistry Leader, Lutz Müller, Toxicology Leader, and many more dedicated experts, got to work. Working closely together with the PTC and SMAF teams, the partners built on the initial breakthroughs and created a molecule optimised for success in clinical trials.
After three years of pre-clinical research with PTC followed by two and a half years in the laboratory, a medicine was discovered, giving hope to thousands diagnosed with SMA, including Arya.
"Partnership excellence has been key to the SMA programme, with each partner contributing their unique capabilities and skills to the overall mix,” says Paulo Fontoura, MD PhD, Senior Vice President, Roche Global Head Neuroscience, Immunology, Ophthalmology, Infectious and Rare Diseases Clinical Development. “This success would not exist without the brilliant original insight and tremendous work done by PTC to attempt what did not seem possible: selectively modifying RNA splicing with a small molecule chemical and building a whole screening platform to achieve that.”
Medicines are discovered in labs, but it requires enormous effort, scientific rigor and creativity to bring them to patients.
“Roche’s world-class medicinal chemists and toxicologists, fueled by the vision of the SMAF and relying on PTC’s pioneering scientific platform, created a 'magical' molecule that breaks all the conventional rules, but achieves the selectivity, potency and safety parameters for human testing,” Paulo explains. “Then, our many colleagues from clinical science, biometrics, clinical operations, safety, regulatory, clinical pharmacology, biomarker research and many more, designed and executed the largest global programme in SMA to date, with the broadest population, and got us from first patient in to US approval in less than four years, instead of the usual 8-10 years. This achievement is nothing short of monumental.”
The combined science and commitment of PTC and Roche, inspired by the passion of the SMAF, led the three partners to a shared vision: to deliver for children and adults living with SMA a transformative new medicine, one that expanded the possibilities of science and led to a scientific breakthrough. Moreover, it provided a treatment for many people like Arya, and will impact countless lives in the future.
SMA Fact File:
SMA is caused by a defect in a gene called SMN1, the main gene responsible for creating SMN protein
Depending on the severity, or type of SMA, people with the disease will have difficulties moving, eating, and in some cases breathing, making them increasingly dependent on parents and caregivers
People with SMA have reduced levels of the SMN protein, which plays a critical role in the survival of motor neurons, nerve cells found in the spinal cord that are responsible for controlling muscle movement
When SMN protein levels are reduced, motor neurons are unable to send signals to the muscles, causing them to become smaller and weaker over time
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