News 
Market Data 
Discover
Replies to post #19048 on NorthWest Biotherapeutics Inc (NWBO)
One contentious issue has been assessment of end points that were not specified as primary in a trial,11 when the specified primary end point failed. In general, the CRAC has agreed with cautious statistical arguments that accepting such unspecified end points would unacceptably increase the study’s “alpha error. ” An exception that provides insights into the difficult nature of the questions the committee often faces was the consideration of carvedilol for postinfarction treatment of left ventricular dysfunction (based on the CArvedilol Post infaRction survIval COntRol in LV dysfunctioN [CAPRICORN] study12). In this case, the committee recommended approval on the basis of an unspecified but statistically significant survival benefit (it had been specified but was changed midstudy) that was supported by a great deal of external data on ß-blockers after infarction and the effect of carvedilol in heart failure.13
The FDA, in general, has viewed a single positive trial with a P<0.05 as a relatively weak indicator of efficacy and has therefore expected >1 positive study for most new drugs. It has, however, accepted single studies that were statistically persuasive, especially for survival, for which conducting a second study would be ethically difficult.
Kamada plans to move ahead with inhaled AAT despite failure to meet endpoints in Phase 2/3 study.
Kamada has announced that still plans to hold discussions with the EMA and FDA regarding regulatory submissions for its inhaled Alpha-1 antitrypsin (AAT) even after the drug failed to meet either its primary or secondary endpoints in a Phase 2/3 clinical study of inhaled AAT for the treatment of Alpha-1 antitrypsin deficiency (AATD).
The company said that inhaled AAT showed no statistically significant difference from placebo in time to first moderate or severe exacerbation, the primary endpoint, as announced earlier this year, and that final analysis showed that the drug also failed to meet secondary endpoints, “time to first event-based exacerbation with a severity of mild, moderate or severe” and “severity of the first exacerbation event.”
However, Kamada said, FEV1 and other lung function parameters “which were collected to support safety endpoints, showed concordance of a potential treatment effect in the reduction of the inflammatory injury to the lung that is known to be associated with a reduced loss of respiratory function.” The company also noted that intravenous AAT therapies were approved based on PK and safety data alone.
Kamada Co-Founder and CEO David Tsur commented, “We strongly believe the clinically meaningful differences seen in lung function parameters are therapeutically relevant, particularly with regard to the most frequent exacerbators, who have the greatest need for effective new therapies and comprise a major portion of this orphan patient population. Based on orphan designation of the drug, prior discussions held with the regulator, the strength of these data and the persistent unmet need in this orphan indication, we will advance our discussions with the European Medicines Agency with the intent to submit for conditional approval in order to bring our inhaled AAT to patients with AATD in Europe, and will initiate discussion with the FDA to determine a US path for registration.”
Tsur added, “We remain committed to AATD patients worldwide and to maintaining our leadership role in the development of innovative new therapies for this orphan lung disease. As such, we remain steadfast in conducting continued clinical work in support of our inhaled AAT, including our ongoing open-label extension study in Europe and Phase 2 US study, as well as other future studies that would support its global licensure and expand its use into other lung diseases. Moreover, these very promising data put us in an attractive position as we advance our ongoing discussions with partners for potential licensing opportunities in markets outside of Europe.”
Alcon plans to submit Retaane to FDA despite failure to meet primary endpoint
(Ref: CBS MarketWatch, The Globe and Mail, Morningstar, TheStreet.com)
October 14th, 2004
By: Candace Hoffmann
Alcon said that it still plans to submit its application for FDA approval of Retaane (anecortave acetate) for the treatment of wet age-related macular degeneration by the end of this year, even though it failed to meet a primary trial endpoint
