Some thoughts and information about NASH as related to CYDY (some of the text below is cut-and-paste from several relevant articles):
In September 2016 Allergan paid an upfront payment of $28.35 per share for Tobira ($1.7Billion) in spite its Phase IIb trial to treat NASH had failed to meet the primary endpoint. Additionally, they throw-in some Contingent Value Rights that might be worth $49.84 per share.
The primary endpoint in the study, with 289 patients, was a drop in a score for disease activity in NASH. The drug failed on this, as well as on the secondary endpoint for complete resolution of steatohepatitis.
What they found was an improvement in fibrosis without any worsening of steatohepatitis: twice as many patients on drug had a marked improvement for fibrosis, but it was a small group.
What Allergan acquired was mainly CVC (CENICRIVIROC), a dual CCR2/CCR5 antagonist which was cataloged as an immunomodulator. They are undergoing P3, however, announced that their results have been delayed until September 2020.
Four candidate drugs are in Phase 3 to date, but Tobira (Allergan) delayed their results, to date only 3 compounds then are still in course for near future approval:
OCALIVA (Intercept) The bad news come from adverse effects: The announced pruritus rate for the only effective dose (25mg/day) is twice that found in phase 2b at equivalent dose. Half of the patients under OCA suffered from pruritus, as this drug is intended to be prescribed to patients for long durations, such a significant side effect is redibitory and will prompt patients to switch to any other medication as soon as it is available. The safety of Ocaliva could be also a concern, three times more patients under OCALIVA have suffered serious events compared to placebo, especially related to gallstones in the liver.
ELAFIBRANOR (Genfit): No safety problem has been detected. The interim result recruitment of 1000 patients was completed in May 2018 and the phase 3 intermediate results are expected Q1 2020. The results recently published PBC (phase 2) have already demonstrated a statistically valid resolution of NASH in phase 2b (GOLDEN), which augurs well for its phase 3.
SELONSERTIB (Gilead) (hang- up announced): GILEAD decided to push their luck a bit and to push forward directly a Phase 3 with a short duration (11 months). Their compound is an ASK1 reducing globally apoptosis of cells in the body and some specialists seem concerned by a possible cancerigen-induced effect. GILEAD announced a failure of STELLAR 4 STELLAR 3
Following the delayed results of CENICRIVIROC (Tobira-Allergan), the failure of SELONSERTIB (Gilead) and EMRICASAN (Conatus) and the disappointing results of ARAMCHOL (Galmed) , only two drugs could dominate the NASH market from 2020 to 2025, OCALIVA, and ELAFIBRANOR.
Two points are relevant here for CYDY: First, the current competition are Genfit and Intecept, however, there are huge unmet needs as NASH has (roughly) 4 stages. However, is a very difficult condition to treat with trials spanning several years and, second, the market size for this mostly unmet need is very large commanding sizable premiums (as the Tobira deal easily probes).
If Leronlimab is to enter the NASH stage, it will need considerable funding and patience. Maybe neither of these are currently present and therefore licensing Lero, even at sub-optimal conditions, would make sense as the moneys could be put to good use by advancing many other, swifter trials in potentially very lucrative markets (i.e. Oncology).
In September 2016 Allergan paid an upfront payment of $28.35 per share for Tobira ($1.7Billion) in spite its Phase IIb trial to treat NASH had failed to meet the primary endpoint. Additionally, they throw-in some Contingent Value Rights that might be worth $49.84 per share.
The primary endpoint in the study, with 289 patients, was a drop in a score for disease activity in NASH. The drug failed on this, as well as on the secondary endpoint for complete resolution of steatohepatitis.
What they found was an improvement in fibrosis without any worsening of steatohepatitis: twice as many patients on drug had a marked improvement for fibrosis, but it was a small group.
What Allergan acquired was mainly CVC (CENICRIVIROC), a dual CCR2/CCR5 antagonist which was cataloged as an immunomodulator. They are undergoing P3, however, announced that their results have been delayed until September 2020.
Four candidate drugs are in Phase 3 to date, but Tobira (Allergan) delayed their results, to date only 3 compounds then are still in course for near future approval:
OCALIVA (Intercept) The bad news come from adverse effects: The announced pruritus rate for the only effective dose (25mg/day) is twice that found in phase 2b at equivalent dose. Half of the patients under OCA suffered from pruritus, as this drug is intended to be prescribed to patients for long durations, such a significant side effect is redibitory and will prompt patients to switch to any other medication as soon as it is available. The safety of Ocaliva could be also a concern, three times more patients under OCALIVA have suffered serious events compared to placebo, especially related to gallstones in the liver.
ELAFIBRANOR (Genfit): No safety problem has been detected. The interim result recruitment of 1000 patients was completed in May 2018 and the phase 3 intermediate results are expected Q1 2020. The results recently published PBC (phase 2) have already demonstrated a statistically valid resolution of NASH in phase 2b (GOLDEN), which augurs well for its phase 3.
SELONSERTIB (Gilead) (hang- up announced): GILEAD decided to push their luck a bit and to push forward directly a Phase 3 with a short duration (11 months). Their compound is an ASK1 reducing globally apoptosis of cells in the body and some specialists seem concerned by a possible cancerigen-induced effect. GILEAD announced a failure of STELLAR 4 STELLAR 3
Following the delayed results of CENICRIVIROC (Tobira-Allergan), the failure of SELONSERTIB (Gilead) and EMRICASAN (Conatus) and the disappointing results of ARAMCHOL (Galmed) , only two drugs could dominate the NASH market from 2020 to 2025, OCALIVA, and ELAFIBRANOR.
Two points are relevant here for CYDY: First, the current competition are Genfit and Intecept, however, there are huge unmet needs as NASH has (roughly) 4 stages. However, is a very difficult condition to treat with trials spanning several years and, second, the market size for this mostly unmet need is very large commanding sizable premiums (as the Tobira deal easily probes).
If Leronlimab is to enter the NASH stage, it will need considerable funding and patience. Maybe neither of these are currently present and therefore licensing Lero, even at sub-optimal conditions, would make sense as the moneys could be put to good use by advancing many other, swifter trials in potentially very lucrative markets (i.e. Oncology).
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