Last week, Saniona announced that the FDA had granted Orphan Drug Designation (ODD) for the drug candidate Tesomet for the treatment of Prader-Willi syndrome (PWS). A few days later, a different Division at the FDA returned with positive feedback on the regulatory path forward in the rare disease of hypothalamic obesity. Saniona now looks set to follow its planned timeline and start phase IIb studies in both PWS and HO before the summer. BioStock reached out to Rudolf Baumgartner, M.D., Chief Medical Officer and Head of Clinical Development at Saniona, for a comment.
Saniona is advancing its primary drug candidate Tesomet – a fixed-dose combination of the triple monoamine reuptake inhibitor tesofensine and the beta-blocker metoprolol to its next stage of clinical development in both hypothalamic obesity (HO) and Prader-Willi syndrome (PWS), two rare diseases that, currently, lack approved treatment options.
Saniona has recently made significant progress in several of its preparations for Phase IIb studies, including now receiving positive clinical development feedback from the FDA in both indications.
»Altogether, we were delighted to receive this feedback from the FDA, which ultimately allows us to continue with our overall planned clinical program without delay« – Rudolf Baumgartner, CMO and Head of Clinical Development Saniona
The CMO comments
BioStock reached out to Boston-based Rudolf Baumgartner, M.D., Chief Medical Officer and Head of Clinical Development at Saniona, for comments on the latest feedback from the FDA.
In November 2020, Saniona communicated positive topline results from the open label extension of the phase II study with Tesomet in hypothalamic obesity. This was encouraging news ahead of the upcoming supportive phase IIb study that the FDA has called for. What specifically in these results would you like to highlight as extra interesting?
– It’s important to remember that hypothalamic obesity represents a significant unmet need, with no approved treatments available. The efficacy data in our completed Phase 2 trial of Tesomet in hypothalamic obesity, conducted at the Copenhagen University Hospital, a center of excellence for the study of HO, indicated that Tesomet treatment resulted in both clinically and statistically meaningful improvements in body weight. To recall, the trial was a 24-week, double-blind, randomized, placebo-controlled study in HO patients.
– Tesomet was well-tolerated, and treated patients demonstrated statistically significant reductions in body weight and clinically meaningful improvements in waist circumference and glycemic control. These improvements were maintained during an additional 24-week open-label extension, with no clinically meaningful differences in heart rate or blood pressure observed between the treatment group and the placebo group. These data are very encouraging, and we look forward to advancing our clinical program in HO.
Earlier this week, FDA got back to Saniona, providing a regulatory path forward for Tesomet in HO. Can you briefly guide our readers through FDA’s recommendations?
– We were very pleased by the feedback we received from the FDA clarifying the path for Tesomet in hypothalamic obesity, and we are progressing forward as planned with the initiation of the Phase 2b trial during the first half of this year.
– Last fall, the FDA highlighted the potential for off-label use of Tesomet in the general obese population. Saniona subsequently submitted a robust package of data and proposals to the agency addressing this concern, and they have now replied that they generally agree with our proposals.
– Specifically, the FDA indicated overall agreement with our Risk Evaluation and Mitigation Strategy (REMS) proposal to mitigate the risk of off-label use, which is a common approach in rare diseases. The agency also said Saniona should demonstrate that HO fulfills the criteria for an unmet medical need, which is consistent with the fact that there are no FDA-approved medicines for HO. As Saniona is pioneering the path forward in HO, it is customary and expected that the responsibility of establishing the unmet need in a new disease area is that of the pioneering sponsor.
»As part of our process of submitting for Orphan Drug Designations, we have recently conducted new analyses to verify the size of the PWS and HO patient populations. We do believe both of these indications, while clearly rare diseases, may impact more people than we initially suspected«
– Another important area where the FDA generally agreed with our proposals was on cardiovascular monitoring. The agency had originally mentioned the possibility of a cardiovascular outcomes study, which might typically involve thousands of patients over several years and would be extremely costly. Saniona proposed instead that as a next step we conduct 24-hour ambulatory blood pressure monitoring (ABPM) and Holter (electrocardiogram) monitoring, which we anticipate could be collected in only a few hundred patients over a few months, and thus would be far more efficient.
– The agency agreed these data could be useful, and–importantly–they said we could gather these data in general obese patients. This is very important because ABPM monitoring can be quite disruptive to a patient’s day-to day-life, such that these ABPM trials are associated with very high dropout rates. Therefore, the FDA, by allowing us to collect this data in general obese subjects, have actively helped us minimize the loss of HO patients in our upcoming Phase 2b trial and allowed us to gather the data in a much faster and more efficient manner.
– Altogether, we were delighted to receive this feedback from the FDA, which ultimately allows us to continue with our overall planned clinical program without delay.
As with PWS, you plan to start phase IIb studies in the first half of 2021. What work has been done to prepare for these studies?
– The Saniona team has made significant progress in preparing for the Phase 2b trials in both PWS and HO. Importantly, we opened an Investigational New Drug (IND) filing with the FDA to support our PWS program and, now that we have alignment on the path forward in HO, we will also open an IND in HO. We have selected the clinical research organization (CRO) that will support the clinical trials in PWS and HO, and we are in the process of assessing and selecting clinical trial sites in the U.S. and globally.
– Some of sites have already identified specific patients they believe would be appropriate for the studies. We have also selected the contract manufacturer to produce Tesomet for Phase 2b and Phase 3 clinical trials, which is important because conducting these larger studies requires the product be produced at a much greater scale. Finally, we have initiated multiple partnerships with the PWS and HO advocacy communities to ensure caregiver and patient feedback is incorporated into the clinical trial process and to provide support to these communities.
Finally, given that there are currently no treatment options for PWS and HO, what does this mean for the market value in monetary terms?
– As part of our process of submitting for Orphan Drug Designations, we have recently conducted new analyses to verify the size of the PWS and HO patient populations. We do believe both of these indications, while clearly rare diseases, may impact more people than we initially suspected. Our new estimates are that PWS impacts an estimated 11,000 – 34,000 people in the U.S. and 17,000 – 50,000 people in Europe, while HO may impact between 10,000 and 25,000 in the U.S. and between 16,000 and 40,000 in Europe. It is too early in our development to speculate about eventual prices or market value, but it is becoming increasingly clear to us that these diseases may impact more people than we initially suspected.
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