VOI News

New Study on Time-to-Peak Sales for US Pharmaceuticals

Drug launch curves in the modern era, a new article in the January 2017 issue of Nature Reviews: Drug Discovery, contains projections of relevance for forecasting pharmaceutical sales in the US market. Relying on unit sales for 61 innovative drugs receiving FDA approval between 2000 and 2002, the authors determined that the median product follows an S-shaped launch-to-peak penetration curve: achieving 11% of peak sales in Year 1, 31% in Year 2, 58% in Year 3, 76% in Year 4, 89% in Year 5, and 100% (i.e. peak sales) in Year 6. On an interquartile basis, time-to-peak (TTP) ranged from 4 to 9 years; the minimum TTP was 2 years and the maximum was 14.

Using data from the Supplemental Materials file we find that the average for TTP for first-in-class drugs is 5.65 years as opposed to 6.93 years for subsequent entrants. Unlike other research on the subject, however, the authors did not that there was a statistically significant relationship between entry order and TTP. But, as they note, TTP is distinct from factors such as market share and revenue potential that may be more indicative of first-mover advantage.

BIO publishes important new report on success rates in drug development

Anyone interested in drug development will want to take a look at Clinical Development Success Rates 2006-2015, a new report from the Biotechnology Innovation Organization (BIO) in partnership with Amplion and Biomedtracker. Per the associated press release, the study “recorded and analyzed 9,985 clinical and regulatory phase transitions, across 1,103 companies” over the past decade to calculate phase-success rates (i.e. the probability of moving forward from Phase 1 to Phase 2, from Phase 2 to Phase 3, etc.) as well as the overall likelihood of approval (LOA).

The results of the BIO study are similar to those reported by Joseph DiMasi and others at the Tufts Center for the Study of Drug Development (CSDD) who looked at 1,442 compounds from 50 leading pharmaceutical firms that initially entered clinical testing between 1995 and 2007. BIO found slightly higher Phase 1 to Phase 2 transition rates but somewhat lower success rates for each step thereafter, leading to an average LOA of 9.6% versus 11.8% as reported by the CSDD. It’s interesting to contemplate whether the higher number of investigational agents moving from Phase 1 to Phase 2 in the BIO study is the reason for lower success rates in subsequent phases. If that is the case, it suggests that the industry needs to work on “failing fast” so that resources are not unnecessarily expended on unpromising candidates.

In addition to aggregate success rates, the BIO report provides detailed figures by disease state and finds that therapies aimed at hematologic or infectious conditions have the highest LOAs (26.1% and 19.1%, respectively) while oncologic and psychiatric agents have the lowest LOAs (5.1% and 6.2%).

Relative success rates for drugs aimed at rare diseases versus those aimed at chronic, high-prevalence conditions were also examined. It turns out that rare drug development programs have a 25.3% LOA as compared to 8.7% for the chronic condition set. The industry shift towards orphan drug development over the past decade is well documented and is frequently attributed to the high prices commanded by therapies for small-population diseases. In forecasting models, however, a three-fold greater likelihood of actually making it to market is almost certainly going to be a bigger driver of net present value than price. The emphasis on orphan drugs has, of course, arisen from a very complex set of factors but improved approval odds are hard to ignore; having these odds quantified in a robust data analysis may well accelerate the flow of development funds towards rare diseases.

The BIO report is free and can be downloaded here.  

The DiMasi / Tufts figures are reported in the May 2016 issue of the Journal of Health Economics.

Drug Development: First-to-market or best-in-class? Which would you rather be?

First mover advantage is a key success factor in many industries and this is certainly true of pharmaceuticals. VOI Consulting research has shown that, in cases where independent generics have a 6-month exclusivity period in which to establish first-mover advantage, the initial product will capture between one-third (with a concurrently-launched authorized generic) and one-half (with no authorized generic) of overall sales value for the molecule 30 months after other generics enter the market. In contrast, later-to-market independent generics capture only 15 to 25% and this is usually divided among multiple entrants.

But these are commodity markets. What about innovative pharmaceuticals? Surely, quality counts for more than timing when it comes to well-differentiated therapies with extensive clinical data. Research from Boston Consulting Group, reported in the June 2013 issue of Nature Reviews Drug Discovery finds that, despite high profile exceptions like Lipitor, this isn’t necessarily the case.

As would be expected, being first and best is the ideal position. The next most favorable position was first-to-market but clinically second best; sales for these drugs average 92% of the first and best product whereas sales of second-to-market but therapeutically superior competitors averaged 88%. Being first isn’t a guarantee of success, however: sales of products that were first-to-market but clinically third-in-class averaged only 40% of the first-and-best product’s while those that were third-to-market but therapeutically best captured 50%.

If you’re late and not-so-great, don’t bother showing up – products that were fourth-to-market and clinically inferior to competitors captured only 2% of the first-and-best drug’s sales.

Pharma Moving towards Biologics in the Lab and the Market

An interesting article from the April 9, 2012 issue of Genetic Engineering & Biotechnology News summarizes two studies that confirm an industry shift towards biologics over small molecule drugs. Specifically:

[The UK law firm, Withers & Rogers finds that] biologics accounted for 60% of the patents filed by the top 10 pharma companies in 2009…The number of biologic patent applications in ’09 increased by 14.5% from two years earlier, even though ’09 saw 31.5% fewer overall patent filings than ’07.

Further, this trend is paying off at the commercial level. Per KMR Group’s Pharmaceutical Benchmarking Forum:Biologics hold better prospects than traditional small molecules of advancing all the way from the lab to the clinic to the market…more than 25% of large molecules in Phase II between 2006 and 2010 reached the market compared to about 10% of small molecules…12% of biologics were calculated to advance from preclinical to clinical studies, compared with just 2% of small molecule drugs. The biologics percentage clearing each successive clinical review hurdle grows to 17% at Phase I, 27% at Phase II, leaping to 58% at Phase III, and 82% at the registration phase. For small molecule drugs, according to KMR, success was calculated to be 4% at Phase I, 9% at Phase II, 44% at Phase III, and 78% at registration.

Exploring Design Elements of Cancer Pivotal Trials

This is the third in a series of blog posts VOI Consulting will publish based on high-level examination of the company’s new insiteinvestigator™ database. It addresses pivotal trial design for cancer drugs gaining approval during the 2005 to 2011 period.

Pivotal Trial Design

The insiteinvestigator™ database also captures elements of pivotal trial design. Using comparisons between solid tumors and hematological malignancies, the following discussion looks at several of the more important design features: primary endpoints, number of arms, and control types.

Primary Endpoints

Overall survival, defined as the time from randomization until death from any cause, is the FDA’s gold standard for drug approval in the cancer field. From a development standpoint, however, it is the most difficult and costly endpoint to demonstrate as it requires higher patient populations and longer follow-up periods.  As we have seen in the preceding section, the FDA is often willing to accept less than gold standard evidence when doing so will make new therapies available if the data is sufficient to show that these new therapies are both safe and effective.

Indeed, as shown in Figure 1, overall survival served as the primary endpoint in only 18% of all pivotal trials during our time period. Although it was the most common primary endpoint in solid tumors, it still represented just one-third of such trials, barely edging out progression free survival which was the primary endpoint in 29% of solid tumor pivotal trials. More striking is its near-total absence in hematologic malignancies where only 4% of pivotal trials featured overall survival as a primary endpoint. In these cancers, response rate and the closely related duration of response/clinical benefit are the predominant primary endpoints, having been used to support 59% of all approvals.

Figure 1 - Primary Endpoints in Cancer Pivotal Trials 2005-2011

 Insiteinvestigator is VOI’s proprietary database containing detailed information on design, endpoints, populations, size, placement, timelines, efficacy outcomes, and safety results for every pivotal trial supporting a cancer drug approved by the U.S. FDA from 2005 through 2011.

Cancer Drug Approval Requirements

This is the second in a series of blog posts VOI Consulting will publish based on high-level examination of the company’s new insiteinvestigator™ database. It addresses FDA approval requirements for cancer drugs approved between 2005 and 2011. 

Approval Requirements

As a rule, the FDA recommends that applications include data from “at least two adequate and well-controlled clinical trials” as a condition of standard drug approval.[1] In cancer, however, the high degree of unmet medical need and the urgency of offering new treatments for potentially fatal diseases mean that approvals are based on a wide range of clinical data packages.This is demonstrated in Figure 1 which shows that the “two adequate and well-controlled trials” standard is actually an unusual occurrence in cancer as only 2% of all indications received approval using this approach. Indeed, approved applications have been based on pivotal trials ranging from as little as a single Phase I pharmacokinetic study (asparaginase Erwinia chrysanthemi, approved in 2011 as part of a combination regimen for acute lymphoblastic leukemia) to as much as three separate Phase 3 trials (rituximab’s 2006 approval for use with CHOP chemotherapy in newly diagnosed Non-Hodgkin Lymphoma patients).Despite the variance, certain thresholds are evident. For example, 75% of all applications and 56% of orphan indications were directly supported with at least one Phase 3 trial. Standards are predictably higher for non-orphan indications, where 88% of applications included a Phase 3 trial. Of indications approved without Phase 3 support, most were for patients who had failed or who demonstrated intolerance to earlier lines of therapy which is understandable given the limited treatment options available to these groups.In addition to demonstrating the range of required data, Figure 1 also reveals that 59% of all indications were approved with a single Phase 3 trial. Nearly three-quarters of all non-orphan drugs fall in this category and it is the most common scenario for orphan drugs as well. In the absence of specific guidance from regulatory agencies, this may serve as the best available proxy for establishing the scope of a clinical trial program necessary to gain approval.

Figure 1 - Number and Type of Pivotal Trials for Approved Cancer Drugs 2005-2011

 

insiteinvestigator™ is VOI’s proprietary database containing detailed information on design, endpoints, populations, size, placement, timelines, efficacy outcomes, and safety results for every pivotal trial supporting a cancer drug approved by the U.S. FDA from 2005 through 2011.

[1] Guidance for Industry: Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics. Food and Drug Administration. May 2007

Therapeutic Cancer Vaccines Webinar

Todd Clark, President of VOI Consulting, will be participating in a webcast hosted by Clinipace Worldwide on Tuesday, December 6, 2011 at 2:00 pm EST. The webcast, “Game Plan for Therapeutic Cancer Vaccines,” will address the nuances of clinical trials in the rapidly growing field of cancer vaccines. Using findings from  VOI’s new insiteinvestigator database, Todd will be covering aspects related to the size, location, timing, and accrual of vaccines trials and how these factors compare to trials of other cancer drugs. Registration is free and can be accessed at http://clinipace.com/webcast-game-plan-for-therapeutic-cancer-vaccines.htm.