(Article taken from PropThink website)
There are some key lessons that can be garnered from this analysis. First, sponsors who have successfully conducted studies that have met the predefined outcomes in a SPA agreement are highly unlikely to be rejected on the grounds that more clinical data/studies are required. In 2012, applicants with successful SPA studies forming the basis of a submission had a 100% approval rate (5/5). Unlike conventional sponsors, there is de minimis risk that they will be required to perform a further confirmatory study to gain approval. It is extremely important to understand the study design and underlying assumptions that have been agreed upon when determining if a study has, in fact, met the conditions for the SPA or not. Statistically significant does not always equal clinically meaningful.
Second, a successful SPA-backed NDA does not guarantee approval on the first regulatory review cycle. Companies submitting a clinical dossier with a SPA can still receive complete response letters. Just because a drug is efficacious does not mean that it is safe; the overall safety risk profile is the primary focus from a regulatory perspective and must be considered when evaluating positions.
Aafia Chaudhry, MD
Safety not an issue with Vascepa...Everything is political,so if the powers that be want Vascepa approved and a positive advisory vote to happen,then it will be approved-
Hopefully Joe Z offered the decision makers more money under the table than Amarin's competitors did.
No office of government is beyond dirty tricks,bribery and payoffs..
Not only did Vascepa meet its trial endpoints under the SPA, as a bonus at the higher dose level it significantly lowered LDL levels 6% over baseline. The biggest concern that the FDA has is the issue of safety. The benefits need to outweigh the risks by some arbitrary measure.
Vascepa has got to be one of the safest drugs of all time as its side effects do not differ from placebo. For the FDA to negate the SPA and require Amarin to wait until 2016, but more importantly potentially negatively affect tens of millions who wouldn't have ready access to the drug, would be utter insanity.
I've been here since March of 2012.
Some of what I have witnessed here most certainly may be labeled, "utter insanity".
Bad choice of words on your part, IMHO, although I totally agree with your "rationale".
Sentiment: Strong Buy
The one rejection in 2012 under an SPA (Trials did not meet endpoints)
Ariad/Merck: Ridaforolimus for Advanced Soft Tissue Sarcoma
Ariad (ARIA) initially requested a SPA in March 2007 and finally reached agreement on a pivotal study design in August 2007. The Phase 3 randomized, placebo-controlled, double-blind SUCCEED (Sarcoma Multi-Center Clinical Evaluation of the Efficacy of Ridaforolimus) study examined the use of oral ridaforolimus as maintenance therapy in patients with metastatic soft-tissue or bone sarcomas who previously had a favorable response to chemotherapy. The primary end point was progression free survival (PFS) with overall survival (OS) and other measures of tumor response as secondary outcome measures. Importantly, in the agreed-to SPA protocol, the applicant estimated that the median time to PFS was 6-9 months and projected a 25% improvement in PFS. This translated into an increase in median PFS from 6 to 8 months or from 9 to 12 months with ridaforolimus. In communications to the sponsor, FDA stated: “Of note, PFS is not proven to be a surrogate for survival in this disease setting. A statistically significant difference in PFS may not necessarily represent a clinically meaningful difference. Whether PFS supports approval will be a review issue and would depend on the magnitude of the improvement and the risk/benefit ratio.” In January 2011, Ariad reported positive results from the SUCCEED study. However, on close examination of the results, ridaforolimus treatment resulted in a statistically significant 21% (3.1 week) improvement in median PFS (ridaforolimus, 17.7 weeks vs. placebo, 14.6 weeks). This was short of the 25% projected improvement in the SPA agreement, and the absolute magnitude of PFS benefit was only 3 weeks compared with the projected 2-3 month benefit assumption, with no significant improvement in overall survival. Nonetheless, Merck (MRK) submitted an NDA in August 2011, which was accepted for standard review in October, 201
In 2013 though we have tivo (from AVEO) being rejected for not showing an OS benefit despite having a SPA accepting PFS as the endpoint.
The trial clearly hit the SPA based endpoint. The main issue was clearly that the FDA spat on the SPA.
Nonetheless, Merck (MRK) submitted an NDA in August 2011, which was accepted for standard review in October, 2011. The NDA was reviewed by the Oncologic Drugs Advisory Committee on March 20, 2012, resulting in a vote of 13:1 against approval. The committee voiced concerns regarding the relative efficacy toxicity profile, citing the modest PFS benefit and high rate of treatment discontinuations and serious adverse events in the context of a maintenance therapy setting. On June 5, 2012, Merck received a CRL stating that additional clinical trial(s) would need to be conducted to further assess safety and efficacy.