[Ed. This is the fourth part in Wayne’s series. You can access the whole thing by clicking here. Please leave comments or questions on the blog and Wayne will address them in future posts in this series.]
Very few independent Canadian biotech companies have successfully completed the development of a novel drug – so my first comment is congratulations to Theratechnologies. Now, let’s study what they did so we can learn how to assess other companies attempting the same feat. To repeat, my approach is to start at the end – regulatory approval – and study the pathway to that endpoint.
The FDA approval states that EGRIFTA™ (tesamorelin for injection) is indicated for the reduction of excess abdominal fat in HIV-infected patients with lipodystrophy. This approval is based primarily on proof of safety and efficacy from the Phase 3 trials. In order to determine their Phase 3 clinical strategy, Theratechnologies ran Phase 2 trials for a variety of indications, including COPD, sleep disorders, HIV-lipodystrophy, hip fractures, type 2 diabetes and flu vaccinations. They chose HIV-lipodystrophy as the best entry point for the commercialization of tesamorelin and may have considered the following factors in choosing this strategy.
- Relative strength of the Phase 2 data for the various indications
- Probability of success in Phase 3
- Ability to recruit patients for the Phase 3 trials
- Easily defined and measured clinical endpoints
- Market potential for each indication
- Interest of potential commercial partners for each indication
These are typical strategy and structure questions which help assess the risks and rewards about any pending or ongoing Phase 3 clinical trial program. We will look at quantifying potential rewards and more complete assessment of risks later in the series.
Here is a list of some clinical and regulatory events which occurred during the Phase 3 trials and subsequent regulatory review of tesamorelin (pulled from various AIFs in about 20 minutes).
|
Year
|
Month
|
Event |
|
2004
|
June
|
Announced Phase 3 clinical strategy |
|
2005
|
March
|
FDA approval to start first Phase 3 trial |
| |
June
|
First patient enrolled in first Phase 3 trial |
|
2006
|
March
|
Patient enrolment completed in first Phase 3 trial |
| |
August
|
SPA for second Phase 3 trial |
| |
October
|
Last patient in first trial completed 3 months of treatment |
| |
December
|
Positive 3-month data from first Phase 3 trial |
|
2007
|
January
|
Started patient enrolment in second Phase 3 trial |
| |
May
|
52-week treatment completed in last patient in first Phase 1 trial |
| |
September
|
Completed enrolment in second Phase 3 trial |
| |
October
|
Positive 52-week data from first Phase 3 trial |
|
2008
|
April
|
26-week treatment completed in last patient in second Phase 3 trial |
| |
June
|
Positive 26-week data from second Phase 3 trial |
| |
October
|
EMD Serono licensed U.S. rights to tesamorelin |
| |
December
|
Positive 52-week data from second Phase 3 trial |
|
2009
|
May
|
Filed New Drug Application (NDA) |
| |
November
|
Announced that the FDA will schedule an advisory committee meeting |
|
2010
|
January
|
Announced that FDA will reschedule advisory committee meeting due to administrative delay at FDA |
| |
May 25
|
Briefing documents for advisory committee released |
| |
May 27
|
Advisory committee meeting; 16 – 0 vote in favour of recommending FDA approve tesamorelin |
| |
November
|
EGRIFTA (tesamorelin for injection) approved by the FDA for the treatment of HIV-lipodystrophy |
By looking at this list, we can create a general list of Phase 3 questions. It is unlikely that any company will answer all or even most of these questions, so other sources such as analyst reports are useful.
- How many Phase 3 clinical trials will be needed?
- How many patients will have to be enrolled in these trials?
- Will the trials be run concurrently or consecutively?
- How long do you expect patient enrolment to take?
- What is the timing of the interim analyses at which an independent board will assess continuance of the trials?
- How long do you have to treat and follow the final patient before you can compile the final data?
- What delay do you expect from the time top-line final data is released until an NDA (or BLA) can be filed?
- Will the NDA be subject to accelerated or standard review timelines?
- What will the cost of these clinical trials be, exclusive of ongoing corporate expenses?
The most complete outline of the clinical trial structure is contained in the Investigators Brochure and Clinical Trial Protocol but these are confidential company documents. The best current disclosure on trial structure is usually found at http://clinicaltrials.gov. This searchable database can be used to find the structure of a specific clinical trial, all clinical trials for specific medical conditions, the drugs being tested in those trials (competition information) and much more.
For the biotech investor, run a historic price chart for TSX:TH, plot all of the events in the table above and see what effect, if any, there was on the share price. If you did this for several companies that took products through Phase 3, whether successful or not, you may be able to spot some trends on what events you think impact share prices. Remember that share prices will also be impacted by other factors including company financings, announcements from competitors, sector trends and global financial events.
Welcome to your Monday Biotech Deal Review for Janary 6, 2014! Happy New Year! Things in 2013 slowed considerably as we approached the holiday season, however January has gotten off to a good start.
The Cross-Border Biotech Blog 