Zogenix, Inc. (NASDAQ:ZGNX) announced new data demonstrating effectiveness and cardiovascular-related safety for patients treated with ZX008 (low-dose fenfluramine) as an adjunctive therapy for seizures associated with Lennox Gastaut Syndrome (LGS), and continued effectiveness and safety for the on-going open-label patients with Dravet syndrome.  The data were presented at the 70th Annual American Epilepsy Society (AES) meeting, taking place this week in Houston, Texas.

The LGS data presented were from an interim analysis of the first 13 patients to have completed at least 12 weeks of a Phase 2 open-label, dose-finding investigator-initiated study, led by Lieven Lagae, M.D., Ph.D., Professor at the University of Leuven, Belgium, Head of the Pediatric Neurology Department and Director of the Childhood Epilepsy Program at the University of Leuven Hospitals.  Patients enrolled in the study were 3-18 years of age diagnosed with LGS with at least four convulsive seizures and on at least two anti-epileptic drugs (AEDs) at stable doses in the four weeks prior to study initiation.  Participants were treated with ZX008 as an add-on therapy for up to 20 weeks starting at 0.2mg/kg/day.  The dose could be titrated at four-week intervals based on treatment response up to a maximum of 0.8 mg/kg/day (maximum daily dose in the trial could not exceed 30mg/day) if the patient did not reach at least a 50% reduction in major motor seizure frequency.  It is important to note that, per protocol, dose escalation stopped when a patient’s major motor seizure frequency was reduced by ≥50% of baseline.  The mean age of participants was 11.4 years (± 4.4) and they had failed a median of five antiepileptic therapies (range: 3-7) prior to this study.  At study initiation, patients were receiving a median of four antiepileptic therapies.  The median number of major motor seizures (defined as generalized tonic-clonic, tonic, atonic, and focal seizures with a motor component) during the four-week baseline period was 60 (range 21-1360). In the Intent-to-Treat (ITT) patient population (n=13), there was a median 50% reduction in seizure frequency over the entire treatment period compared to baseline (range: +74% to –90%), with seven patients (54%) to date achieving a ≥ 50% reduction (range: 50% to 90%) in the number of major motor seizures in this step dose study.

There were no cardiovascular-related adverse events observed. The most common treatment-related adverse events were decreased appetite (n=3), decreased alertness/fatigue (n=3) and insomnia (n=2).  Three patients withdrew due to adverse events (decreased alertness (n=2) and insomnia (n=1) and one patient withdrew due to lack of effect (the patient was initially a responder, but lost response after undergoing surgery during the trial).

“These initial results for ZX008 in LGS are quite compelling for this refractory group of patients,” said Professor Lagae.  “A significant unmet medical need currently exists in the treatment of LGS and these initial data indicate that ZX008 has the potential to be a safe and effective adjunctive treatment for this rare pediatric epilepsy condition.  I look forward to continuing to evaluate ZX008 in this ongoing Phase 2 open-label study.”

The Dravet syndrome data highlighted updated results from the ongoing prospective study in Belgium with the new patient cohort (n=9). All of these patients began add-on treatment with low-dose fenfluramine (5 mg to 20 mg per day) at various starting points between 2010 and January 2016.  Median treatment duration was 2.1 years (range 0.8 to 5.6 years).  During the 90-day run-in period prior to initiating low-dose fenfluramine treatment, the median frequency of major motor seizures (defined as tonic, clonic, tonic-clonic, atonic, and myoclonic seizures lasting >30 seconds) was 15.0 per month (range 0.4 to 39.7).  Over the entire observation period, the median frequency of major motor seizures was reduced to 1.9 per month, and the median decrease was 76% (range 20-95%). Six of the nine patients (67%) had at least a 70% reduction in major motor seizures.  In addition, regarding durability of effect, six of the nine patients (67%) experienced a ≥50% reduction in seizure frequency for at least 90% of the months they were being treated.

Treatment with low-dose fenfluramine continues to be generally well-tolerated.  The most common treatment-emergent adverse events were mild-to-moderate somnolence (n=5) and anorexia (n=4).  No evidence of cardiac valvulopathy or pulmonary hypertension was observed in any patient on any echocardiogram.  There were no patient discontinuations.

Two additional posters were also presented in the main exhibit hall at the AES meeting.  One poster presented pre-clinical data suggesting that there may be a protective effect of fenfluramine in an accepted pre-clinical model of Sudden Unexpected Death in Epilepsy (SUDEP). In this SUDEP animal model, the administration of fenfluramine significantly (p<0.05) reduced the susceptibility of the mice to have seizure-induced respiratory arrest (S-IRA) 30 minutes post-dosing (20 or 30 mg/kg i.p.) and maintained significance through 24 hours.  The prolonged effect of fenfluramine in the present study was not consistently observed with other serotonergic agents tested. These data provide the first evidence of a protective effect of fenfluramine in a mammalian model of SUDEP.

The second poster highlighted the findings from roundtable discussions with parents and caregivers of children with Dravet syndrome that sought to identify those aspects of caregivers’ lives that are most impacted by caring for a child with Dravet syndrome.  These roundtable discussions identified significant impacts on the lives of these families in four overarching areas: physical, mental, social, and financial.  Future work by this group will focus on developing a validated measure of caregiver burden in Dravet syndrome.

“The Zogenix team is extremely pleased with all of the data presented at this year’s AES meeting,” said Stephen J. Farr, Ph.D., President and CEO.  “Based on the strength of the LGS data generated, we are currently evaluating a move into a Phase 3 program of ZX008 in this indication.  In Dravet syndrome, our confidence in the potential of ZX008 as a safe and effective treatment for seizures associated with Dravet syndrome continues to strengthen with the meaningful reduction in seizure frequency and sustained cardiovascular safety that remain consistent in the results observed in the new cohort of patients.  Additionally, the preliminary data generated in the animal model of SUDEP, which suggests a protective effect of fenfluramine against seizure-induced respiratory arrest, is an interesting finding that we intend to explore further.”

Zogenix also hosted a Scientific Exhibit Room at the AES meeting entitled, “Evolution of Low-Dose Fenfluramine in the Treatment of Epileptic Encephalopathies: New Understandings of the Mechanisms, Basic Science, and Clinical Data.”  In this Scientific Exhibit Room, the Company highlighted important ZX008-related research conducted over the last year, including multiple scientific posters that were not presented in the main poster session of the AES meeting.

Zogenix’s Phase 3 program for Dravet syndrome continues to enroll patients in the U.S. and internationally, and the Company expects the availability of Phase 3 top-line data in Dravet syndrome in the second quarter of 2017, and potential regulatory submissions for approval to occur by year-end 2017.  ZX008 is designated as an orphan drug in both the U.S. and Europe, and also received Fast Track designation in the U.S., for the treatment of Dravet syndrome. (Original Source)

Shares of Zogenix closed last Friday at $13.05, up $0.35 or 2.76%. ZGNX has a 1-year high of $15.49 and a 1-year low of $7.33. The stock’s 50-day moving average is $8.95 and its 200-day moving average is $9.29.

On the ratings front, Zogenix has been the subject of a number of recent research reports. In a report issued on November 7, Oppenheimer analyst Rohit Vanjani assigned a Buy rating on ZGNX, with a price target of $16, which represents a potential upside of 23% from where the stock is currently trading. Separately, on the same day, Leerink Swann’s Paul Matteis reiterated a Buy rating on the stock and has a price target of $17.

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Rohit Vanjani and Paul Matteis have a yearly average return of 7.5% and 7.2% respectively. Vanjani has a success rate of 52% and is ranked #428 out of 4240 analysts, while Matteis has a success rate of 52% and is ranked #603.

Zogenix, Inc. is a pharmaceutical company, which is engaged in commercializing and developing products for the treatment of central nervous system disorders and pain with novel drug delivery platforms. The company’s product portfolio includes: Sumavel DosePro, Zohydro and Relday. The Sumavel DosePro product offers fast-acting, easy-to-use subcutaneous administration of sumatriptan for the acute treatment of migraine and cluster headache. The Zohydro product is a 12-hour extended-release formulation of hydrocodone without acetominophen for the treatment of moderate to severe chronic pain requiring around-the-clock opioid therapy. The Relday product is a proprietary, long-acting injectable formulation of risperidone using durect’s SABER controlled-release formulation technology in combination with its DosePro needle-free, subcutaneous drug delivery system.