Gene therapy clinical holds take centre stage
An analysis of company disclosures reveals a sharp rise in US FDA-imposed halts on clinical work involving gene therapies.
After the recent flurry of US clinical holds you might be excused for thinking that such setbacks are on the rise; in fact, data from the past three years do not bear out such a view. What they do show, however, is an alarming increase in the number of holds imposed specifically on gene therapies.
This could simply reflect the increased work on novel approaches versus three years ago, but the inescapable fact is that holds imposed on gene therapies increased from one in 2017 to four last year and eight so far in 2019. This includes a few repeat offenders, most notably Solid, of whose clinical hold on SGT-001 investors were again reminded this week.
Remarkably, Solid is now on its third clinical hold. Yesterday the group played up the fact that the adverse event that had led to this had now resolved, and that two earlier subjects were seeing microdystrophin expression potentially supportive of a therapeutic benefit in Duchenne muscular dystrophy.
However, the hold remains in place, and on an analyst call Solid would give no guidance on when it might be lifted. And, when it is, investors have to deal with the separate question of why so far the microdystrophin expression levels SGT-001 has been yielding have lagged those of Solid’s rival, Sarepta.
|Three years of US clinical holds|
|By project type|
|By hold type|
|By reason for hold|
|Source: company statements, filings & EvaluatePharma.|
The above analysis of the past three years’ holds was carried out using EvaluatePharma, by way of a database search of disclosures made by biopharma groups in press releases, quarterly reports and SEC filings, as well as those reported in stories published by Vantage.
The list might not be exhaustive though it should present an accurate picture. It likely omits work under way at academia and at private companies, which naturally have a lower disclosure burden than those traded on the public markets.
There is also the risk that the searches missed some announcements that did not specifically mention the phrase “clinical hold”, or indeed that some listed biotechs have not even disclosed such information – an inexplicable decision given the market-sensitive nature of such setbacks.
That this is a possibility was illustrated by recent holds imposed on Regenxbio, Abeona and Marker Therapeutics, the last not involving a gene therapy, all of which sat on FDA notification of a clinical hold for weeks. Most famously, perhaps, Solid itself initially did not disclose a clinical hold while trying to complete its Nasdaq flotation (DMD-day for investors, January 26, 2018).
With some companies choosing not to reveal a clinical hold until a quarterly SEC filing, or until they respond to the FDA’s imposition of such a hold, if anything the absolute number of clinical holds in place might be higher.
|US clinical holds involving gene therapies, 2017-19|
|Nov 2017^||Solid Biosciences||SGT-001||Partial||Manufacturing|
|9 Mar 2018||Advaxis||Axalimogene filolisbac||Full||Death of respiratory failure|
|14 Mar 2018||Solid Biosciences||SGT-001||Full||Bleeding & complement activation|
|30 May 2018||Vertex/Crispr||CTX001||Full||Unknown|
|25 Jul 2018||Sarepta||DMD gene therapy||Full||Manufacturing|
|23 Jan 2019||Advaxis||Axalimogene filolisbac||Partial||Manufacturing|
|15 Apr 2019*||Adverum Biotechnologies||ADVM-022||Full||Manufacturing|
|10 Sep 2019||Prevail Therapeutics||PR001||Full||Modified clinical design|
|23 Sep 2019*||Abeona Therapeutics||EB-101||Full||Needs stability data|
|18 Oct 2019**||Regenxbio||RGX-314 (wet AMD)||Partial||Third-party devices|
|18 Oct 2019**||Regenxbio||RGX-314 (diabetic retinopathy)||Full||Unclear|
|30 Oct 2019||Novartis||AVXS-101 intrathecal||Partial||Preclinical toxicity|
|12 Nov 2019||Solid Biosciences||SGT-001||Full||Toxicity|
|Note: ^not disclosed until Jan 2018; *company had been notified some time before this disclosure date; **not disclosed until Nov 2019.|