Another Annual Report

Recently, I was sent an Annual Review conducted by Citeline Intelligence Solutions. This concise report offers readers a brief summation of pharmaceutical R&D trends and an analysis of industry wide product development strategies and clinical trial success rates. There were not too many talking points amongst the majority of findings presented, however there was the odd statistic that buckled recent trends & a couple of surprise ones that I could not have predicted. Following is a rapid-fire synopsis of their findings:

* A total of 9605 drugs in active development for 2008, a 4.3% increase from the previous year.
* An above average 32 market entrants (New Active Substances) globally, although none of them seem to be really big sellers.
* The US remains the premier market with 15 of 32 debuts.
* Six new biotech product launches for the year.
* In 2007, anticancer drugs accounted for a third of the total launches. In 2008? Despite oncology being the biggest area of R&D, the grand total is a big Zero!
* CNS, the next big R&D area also had a laggardly year with 3 new drugs (but none first in class).
* Cardiovascular & Blood/Clotting disorder drugs had the greatest success with 10 new market entrants. Gastrointestinal drugs come in second with 5 product launches.
* Innovation levels remained discouragingly low with only 1 new market entrant for HIV/AIDS and 2 new anti-infectives.
* At the clinical stage, virtually the entire 4.3% increase in drug candidates is at the preclinical stage. The trends for post-preclinical phases remain flat, with a modest 2.6% increase at Phase II being the only noteworthy statistic.


* More disturbing is the decrease in the number of drugs at the pre-registration and registered but awaiting launch phases.
* 28% of all drugs in development have an anticancer therapeutic activity. 19.8% of the total pipeline has a neurological activity.
* The gradual ascent of biotech continues with 23.7% of the drugs placed under a biotechnology therapeutic category.
* Some positive news is a 6.2% increase in the number of drug protein targets under investigation.
* The J&J Empire, GSK and Genzyme enjoyed the most first launches in 2008.
* GSK remains the biggest company in R&D terms (240 drugs), but looks to surrender this position with the recent mega-mergers.
* The trend seems to be for the biggest companies to have shown slight declines in pipeline sizes, indicating that further segmentation and specialization seems to be the new motto of the industry.
* Despite the financial climate, it is encouraging to see a 6% rise (a total of 2084 companies) in the number of companies involved in pharma R&D. The recession does not seem to have dampened the spirits of start-ups & small companies with 836 of them listing one or two drugs in their portfolios.

Read more...

Pipeline Execution

Parexel consulting just published a new white paper highlighting the key limiting factors in getting new drugs to approval. The paper focuses on perhaps the 2 most critical factors shaping the pharmaceutical industry’s future performance at a time when R&D costs continue to rise in relation to output and ‘safety first’ becomes the dominant principle in the US regulatory environment. The most pressing challenge for industry executives “has shifted from building the pipeline to executing the pipeline”, it comments. The hurdle has resulted in a decade long decrease in submissions of New Molecular Entities (NME's) in the US. After averaging 45+ per year in the mid-1990s, NME filings to the FDA dropped to 21 in 2006. Last year they recovered slightly to 28 submissions. The preliminary results of an FDA study on NMEs released in June indicated that the overall decline may reflect industry’s waning interest in seeking approval for less innovative NMEs.



First Cycle Approval

How much is getting a new drug through the FDA approval process at first attempt worth? About $639.2 million according to Parexel. For NMEs signed off by the FDA in 2007 and the first half of 2008, the approval times for compounds cleared in a single review cycle were less than one third those for NMEs requiring resubmissions (8.6 months versus 27.7 months).

The good : there has been a recent increase in the percentage of US NDAs gaining first-cycle approvals. In the 2006 fiscal year cohort (the latest to mature fully), the FDA’s Center for Drug Evaluation and Research set a record for the user-fee era of approving 51% of NDAs in the first review cycle.

The bad: In FY 2007, nearly a quarter of Class 1 NDA submissions – the less complex refilings in response to minor issues raised in the first-cycle review – failed to gain approval.

The ugly: Close to two-thirds of Class 2 NDA resubmissions – typically filed in response to more significant questions arising in the initial or previous review cycle – during FY2007 did not make it to approval.

Priority Review

Priority review status – usually reserved for drugs with indications where there are no satisfactory alternatives or that offer significant improvements over what is already available- is the second most critical factor that directly correlates with revenue loss. Nearly US$448.4 million worth .

The FDA’s performance goals specify six months for taking action on priority NDAs, compared with 10 months for standard NDAs, the white paper notes. However, the implications of a priority rating are “far more significant” – for example, between 1 January 2006 and 30 June 2008, priority NMEs were cleared on average 13 months ahead of standard-rated NMEs.

Moreover, 94% of the priority NMEs approved in 2006, 2007 and the first half of 2008 were cleared in the first review cycle, while around one quarter of all standard NMEs approved over the same period needed three cycles to get through the process. To make matters worse after granting priority ratings to 30% of the NDAs submitted in 2005, the agency has done so for only 18% of applications filed in FY 2007 and up to 31 March 2008.

Read more...