Clinical trial delays become reality as Covid-19 risk spreads

A Vantage analysis identifies 315 pivotal trials that, like Lexicon’s Scored and Soloist studies, risk never being completed.

Analysis

As the knock-on effect of Covid-19 spreads far and wide, one aspect biopharma investors must consider is the risk that ongoing trials might be delayed or even abandoned. Yesterday Lexicon provided a case in point, cancelling two Zynquista studies that had recently completed enrolment of nearly 15,000 type 2 diabetics.

True, the coronavirus pandemic was only one reason cited, and it is likely that Lexicon largely wanted to end uncertainty and accept that a partner to fund the trials to completion would not be found. But Vantage has identified a further 315 pivotal studies due to end this year, in 172,104 subjects, that might suffer a similar fate.

Among these feature such projects as Pfizer’s Clostridium difficile vaccine candidate PF-06425090, whose Clover study is, with 17,525 subjects enrolled, the biggest in this analysis. A separate PF-06425090 trial, seeking to recruit 1,960, features among the top five studies reading out this year that have yet to enrol fully.

Under threat

A huge amount of clinical work is under threat, and this analysis sought to identify biopharma’s most advanced, and most valuable, crop of R&D assets.

To pinpoint studies with the most invested – in terms of time and money – Vantage searched specifically for pivotal-stage projects that have yet to receive US approval, in trials that have a 2020 primary completion date, according to clinicaltrials.gov.

The topline analysis reveals 168 trials still recruiting, and another 147 that are active but fully enrolled, comprising 64,856 and 107,248 subjects respectively. Remarkably, it looks like at least five near-term blockbusters are under threat: Lilly’s tirzepatide, Reata’s bardoxolone, Immunomedics’ sacituzumab govitecan, Bristol-Myers Squibb’s Tyk2 inhibitor and Galapagos’s filgotinib.

The exposure of Bristol is especially striking: four Tyk2 studies are due to be completed this year, plus another four of ozanimod. The latter project features in the contingent value right issued under the Celgene acquisition; as Stat News has pointed out, FDA review delays could mean that this CVR never pays out.

Blockbusters under threat? Projects in this analysis with biggest projected sales potential
Project Company  2024e sales ($m) Trial under threat? 
Tirzepatide Lilly 1,619 NCT03882970
Bardoxolone methyl Reata 1,608 NCT02657356
Sacituzumab govitecan Immunomedics 1,365 NCT02574455
BMS-986165 (Tyk2) Bristol-Myers Squibb 1,178 NCT03611751; NCT03624127; NCT04167462; NCT03924427
Filgotinib Gilead 1,031 NCT02914522
Ozanimod Bristol-Myers Squibb 966 NCT02576717; NCT02435992; NCT03440372; NCT03440385
Efgartigimod Argenx 964 NCT03669588
Mirikizumab Lilly 848 NCT03535194; NCT03518086
AXS-05 Axsome 753 NCT02741791; NCT04039022
Fintepla Zogenix 694 NCT03355209; NCT02682927; NCT02826863
Source: clinicaltrials.gov & EvaluatePharma sellside consensus.

There are numerous ways in which the Covid-19 situation can hit a clinical trial. A big risk is that patients are lost to follow-up; early analysis is possible, but would require a protocol change. If a database has been locked the problem is less severe, but the actual analysis could be delayed at the CRO.

Already, outside the pivotal setting, many of the first quarter’s expected clinical readouts are in doubt, and Provention Bio, Iveric Bio and Arrowhead are three companies that have recently said they would pause study recruitment (Will pending clinical readouts make it across the line?, March 18, 2020).

In Lexicon’s case the pointlessness of the Scored and Soloist trials, halted yesterday, was perhaps a foregone conclusion. Zynquista is awaiting approval for type 1 diabetes, and the type 2 setting of Scored and Soloist was meant to have opened up its really big market.

However, Lexicon lost Sanofi as a partner, and completing the two trials relied on it finding a new licensee – something that, with the pandemic situation imposing severe restrictions on meetings and the movement of people, must have been seen as impossible.

It is fortunate for sponsors that the US FDA has taken a lead on the problem of trial delays, spelling out its willingness to consider protocol amendments, design changes and alternative methods of study subject assessment. This could be a small mercy, but it is something.

Big phase III trials that are still searching for patients, but should be getting close*
Project (setting) Company  Enrolment  Trial ID
PT027 (asthma) Astrazeneca 3,100 NCT03769090
PF-06425090 (C difficile-associated diarrhoea) Pfizer  1,960 NCT03918629
Mirikizumab (ulcerative colitis) Lilly 1,160 NCT03518086
STS101 (migraine) Satsuma Biotech 1,140 NCT03901482
Vibegron (overactive bladder) Urovant  1,088 NCT03902080
*Assumes that primary completion date is accurate. Source: clinicaltrials.gov.

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