Reata Pharmaceuticals’ dream of becoming the first to secure FDA approval for an effective treatment of Friedreich’s ataxia (FA) has been put on hold after news of the departure of the FDA’s neuroscience head, Dr. Billy Dunn, emerged on Monday. This surprising development has left many in the medical community anxiously waiting to find out what comes next.
On February 28, the Food and Drug Administration will make a decision that could bring relief to those suffering from Friedreich’s Ataxia (FA), a rare and debilitating neuromuscular disorder. If approved, omaveloxolone could become the first disease-modifying treatment available to patients with FA, offering hope for slowing or halting the disease’s progression.
Reata’s stock plummeted in a dramatic plunge of 32% in response to the news of Dunn’s departure, sending shockwaves through the market.
The Case for Omaveloxolone
Omaveloxolone is one of the most highly anticipated potential treatments for neurodegenerative diseases in 2023. This revolutionary drug activates Nrf2, a transcription factor that works to reduce inflammation, restore mitochondrial function, limit oxidative stress, and suppress pro-inflammatory signals. With this revolutionary approach to treating neurodegenerative diseases, omaveloxolone could prove to be a real game-changer in the medical field.
Omaveloxolone proved to be a game-changer in a registrational trial of 103 patients, significantly improving neurological function compared to placebo with an impressive safety profile. Writing in the Annals of Neurology, a group of physicians and Reata representatives reported that the drug was generally safe and well tolerated.
Friedreich’s ataxia is a rare and debilitating disorder that has been affecting approximately 5,000 people in the U.S. since its discovery in the 1860s by German physician Nikolaus Friedreich. This incurable disorder can have a profound effect on the quality of life of those affected and has been the subject of much research in recent years.
Friedreich’s Ataxia is a debilitating neurological disorder caused by a trinucleotide repeat expansion in the first intron of the frataxin (FXN) gene. This expansion reduces the expression of frataxin, a protein essential for the regulation of iron in the mitochondria. Such an iron overload leads to uncoordinated muscle movement and a range of other symptoms.
Patients with Friedreich’s Ataxia (FA) face a difficult prognosis, as the neurological disorder typically progresses from childhood to early adulthood. Sadly, most sufferers succumb to the disease in their mid-thirties, most often due to cardiovascular complications.
Reata is leading the way with their FDA application, but they’re not alone in their pursuit of getting approved. Other companies are hot on their heels, all vying for a chance to make their mark in the world of medical treatments. It’s a race to the finish line, and the stakes are high! Who will come out on top?
PTC Therapeutics: Q2 Readout
PTC Therapeutics is eagerly anticipating the results of the Phase II/III MOVE-FA trial, set to be released in the second quarter of 2023. This highly anticipated data could potentially be a game-changer in the field of therapeutic treatments.
Vatiquinone, an experimental small molecule, is being evaluated for its potential to inhibit 15-Lipoxygenase, a key player in the oxidative stress and inflammation response pathways. By targeting this enzyme, vatiquinone could offer promising therapeutic benefits and open up new avenues for treating a variety of diseases.
Oxidative stress is a critical component of FA disease pathology, resulting in persistent inflammation of neural tissue. This inflammatory response can become chronic, leading to a cascade of damaging effects that can be difficult to manage.
Mitochondria play a critical role in the body, and when they go awry, it can lead to devastating illnesses like Friedreich’s Ataxia. According to Stuart Peltz, Ph.D., CEO, this disease is an example of how mitochondrial dysfunction can impact our health.
Adenosine triphosphate (ATP) is the body’s primary energy source, produced in the mitochondria through an electron transfer chain. However, careful regulation is necessary, as the release of these electrons from the mitochondria can interfere with proteins and DNA, resulting in a loss of function. Dr. Peltz explains that this disruption can have serious implications for our health.
The 15-Lipoxygenase enzyme is a powerful regulator of neuroinflammation, making it a crucial component of maintaining healthy brain functioning. By controlling inflammation in the brain, this enzyme has the potential to play a vital role in preventing a range of neurological disorders, from Alzheimer’s and Parkinson’s to depression and anxiety.
The dysregulation of the mitochondrial electron transfer pathway can have serious consequences, activating the 15-Lipoxygenase pathway and creating an inflammatory milieu that can cause damage to the body. This can lead to chronic inflammation, which can have devastating effects on our health.
Vatiquinone has been proving its efficacy and safety in a Phase II trial, with a statistically significant effect observed at 24 months for over 500 patients. Furthermore, the drug has demonstrated a favorable safety profile, providing further evidence of its efficacy.
Patients with Friedreich’s Ataxia experience a decline of two points annually on the modified Friedreich’s Ataxia Rating Scale (mFARS). However, if clinicians can maintain their patient’s condition and prevent any deterioration, it is considered a positive outcome.
Targeting the Root Cause
Larimar Therapeutics, based in Pennsylvania, is eagerly awaiting topline data from a Phase II trial of its sole clinical-stage product, CTI-1601. CTI-1601 is a recombinant fusion protein, designed to deliver human frataxin into the mitochondria of patients with Friedreich’s Ataxia. Patients and their families can look forward to the promising results of the trial, expected to be released in the second half of 2023.
In healthy individuals, frataxin molecules are transported across the mitochondrial membrane with the help of a small protein sequence. This sequence is then cleaved off by an enzyme, allowing the molecule to enter the mitochondria.
CTI-1601 is a revolutionary breakthrough in the fight against frataxin deficiency, as it is equipped with a special cell-penetrating peptide designed to transport the frataxin molecule directly into the cell and mitochondrial membranes. Carole Ben-Maimon, M.D., President and CEO of CTI-1601, is excited about this breakthrough and the potential it holds for those with frataxin deficiency.
The frataxin protein is designed in such a way that it can be precisely delivered to the mitochondria, the powerhouse of the cell. Its structure contains a cleavage site that allows for the removal of the cell-penetrating and mitochondrial targeting sequences, ensuring that it stays in the right place. This ingenious design enables the protein to do its job of helping to reduce the symptoms of Friedreich’s ataxia.
Larimar is eagerly awaiting the Phase II data readout in anticipation of the safety pharmacokinetics and frataxin levels. The results of Phase I showed that daily injections of CT1-1601 at either 50 mg or 100 mg led to higher levels of frataxin in buccal cells in the skin, which is a promising sign for Friedreich’s Ataxia patients. Ben-Maimon and the team are hoping for a successful repeat of these results.
CTI-1601 is revolutionizing the treatment of Friedreich’s ataxia (FA). Rather than simply addressing the symptoms of the rare neurodegenerative disorder, CTI-1601 targets the root cause of the disease – the lack of frataxin. By replenishing the missing frataxin, CTI-1601 has the potential to significantly improve the lives of those living with FA.
Reata’s omaveloxolone is more than just an antioxidant; it actually activates a powerful protein called Nrf2, which then triggers the production of even more protective proteins. This amazing drug is truly a powerhouse when it comes to protecting cells from damage.