Fennec (FENC) announced that their Phase 3 results, initially released back in October 2017 (read more), were published in the June 21, 2018 issue of the New England Journal of Medicine (NEJM) (abstract).
The publication included the full data set from the study (n=101), so there is some new data (2 more assessable patients) that was not presented back in October 2017 (n=99). Here are the findings:
- 101 children were assessed. The SIOPEL 6 study met its primary endpoint. Sodium thiosulfate (STS), administered 6 hours after cisplatin chemotherapy, reduced the incidence of cisplatin-induced hearing loss in children with standard-risk hepatoblastoma without jeopardizing overall or event-free survival.
- Efficacy: Hearing loss occurred in 18 of 55 children (33%) in the cisplatin-sodium thiosulfate group (“Cis+STS”), compared with 29 of 46 (63%) in the cisplatin-alone group (“Cis”) (p = 0.002).
- Note: P value in full data set (p=0.002) is lower (meaning better) than what was presented in October (p=0.0033).
- Safety: At 52 months follow-up, the 3-year rates of event-free survival were 82% in the Cis+STS group and 79% in the Cis group, 3-year rates of overall survival were 98% and 92%, respectively.
The main takeaways:
- STS protects against hearing loss in children. P-value in full data set is actually lower than the initial data. This means it is even more likely that patient results are due to the drug working and not a random outcome.
- STS is safe to deliver as it is not intervening with cisplatin’s anti-tumor activity in a localized cancer indication. This was initially a concern as the first Phase 3 study (COG ACCL0431) indicated that STS may intervene with the anti-tumor activity of the cisplatin in disseminated cancers.
Real World Impact: STS Improves Quality of Life
With Fennec preparing their NDA for FDA submission in Q4 2018, we analyzed the publication to better understand Pedmark’s (STS commercial name) real world use and impact it has on the quality of life for the children taking it. We believe this is what the FDA will evaluate, in addition to the statistical figures, when reviewing Fennec’s NDA.
Hearing Loss
Children with Brock Grade 0 can manage life with little or no additional help. Those with hearing loss of Grade 1 or higher are offered hearing aids and typically receive further intervention with each increasing grade of hearing loss. This will impact speech, social and educational development.
In this trial, hearing loss of grade 1 or higher occurred in 63% of the children who did not receive STS, as compared with 33% of those who did (figure below).
STS lowers hearing loss risk by 48%, giving children a greater chance of living normal healthy lives.
Adverse Events
Study results showed that adverse events were as expected and similar between the treatment and control arm. One unexpected serious adverse reaction was reported in a child in whom metabolic acidosis (acid imbalance) developed. The STS was stopped and the child recovered. At follow up, the child was alive and free from disease, but developed grade 4 hearing loss. No reason could be found for the unexpected reaction, so the event was considered to be related to sodium thiosulfate.
Interesting note: It took this study roughly 7 years to enroll a total of 116 children at 52 centers in 12 countries. The long duration and difficulty to find patients creates a huge moat for Fennec with a strong barrier to entry for any competing product. We think this adds appeal to Fennec as a takeout target.
Bottom Line: The data confirms that STS works, is safe to administer in a small population (localized hepatoblastoma) and improves quality of life. With FDA breakthrough designation, we think Fennec has a good chance to get FDA approval and then target off label use in children under 5 years of age with localized cancers. Our thesis remains the same: Fennec is positioned for a takeout in the $20/share range.
One or more of PropThink contributors are LONG FENC.
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