Who Is Ahead In The COVID-19 Vaccine Race? – Seeking Alpha

BioNTech SE (BNTX) and Pfizer (PFE), Moderna (MRNA), and AstraZeneca (AZN) and Oxford are leaders in the race for US approval of a vaccine for COVID-19. I feel PFE/BNTX is likely to be the first to report a result from a 30,000-patient US trial, the minimum size of trial the FDA has asked for in order to warrant emergency use authorisation. A look at the potential timelines and progress is nonetheless warranted.

PFE/BNTX's BNT162b2, an RNA vaccine which codes for "an optimized SARS-CoV-2 full-length spike glycoprotein(s)," was selected over BNT162b1 based on the results of an earlier clinical study. BNT162b1 will still be tested by BNTX and Fosun Pharma in China. The PFE/BNTX phase 2/3 study of BNT162b2 consists of two doses, separated by 21 days. PFE and BNTX announced the start of this study on July 27, it contains up to 30,000 participants and includes regions where there is "significant expected SARS-CoV-2 transmission." Looking in such regions is of value as a higher event rate (proportion of those developing COVID-19) will help detect a difference between placebo and BNT162b2.

By August 20, three weeks and three days after initiation, PFE disclosed it had enrolled 11,000 participants in the 30,000-participant study. A second dosing was already underway (which makes sense as the second dose occurs at 21 days). Despite the already rapid enrolment at the time of the August 20 press release, additional trial sites were being opened in Turkey, Germany, and South Africa. By August 26, a PFE scientist reported that the study was now over 50% enrolled (>15,000 participants). PFE/BNTX plans to submit for approval in October if the phase 2/3 study is successful. PFE begins looking at COVID-19 cases to compare the control and vaccine just seven days after the second dose.

Figure 1: Select primary outcome measures from PFE/BNTX's phase 2/3 study. Source: Clinicaltrials.gov.

Now, let's look at MRNA. MRNA announced the 30,000-participant, phase 3 COVE study of mRNA-1273 on July 27. By August 21, MRNA had enrolled 13,194 participants. Enrolment in MRNA's trial was apparently 8,374 in three weeks according to CNN on August 18. That is quite an increase in the rate of enrolment from August 18 to August 21, unless the 8,374 number came from earlier in the third week, rather than the end of the third week. Unfortunately, the CNN article noted concerns MRNA wasn't enrolling enough minorities.

While Black people and Latinos account for more than 50% of Covid-19 cases nationwide, so far they make up only about 15% of participants in the nation's first large-scale clinical trial to test out a coronavirus vaccine, according to data obtained by CNN from a government official.

CNN article by Elizabeth Cohen, August 18, 2020.

With the August 21 update from MRNA came an update with some details on minorities in MRNA's trial.

As of Friday, August 21, Black or African American, Latinx, American Indian and Alaska Native participants make up approximately 18% of all participants in the Phase 3 study.

MRNA COVE study website.

The CNN article discussed the possibility of the COVE study having to slow enrolment to make sure more minorities were being recruited. As such, MRNA is at risk of falling behind PFE/BNTX.

A similar update came on August 28 when the company noted enrolment was now at 17,458. It looks like MRNA has been successful at increasing the proportion of minorities in the trial.

Figure 2: Enrolment trends by week in MRNA's COVE study. The orange proportion represents the percentage of white participants, not the proportion has fallen week to week as enrolment grows, MRNA making efforts to make sure that the trial population is more representative of those impacted by COVID-19 outside of the trial. MRNA COVE study website.

When we consider the trial design of MRNA's COVE study, we see it creates delays in reporting a result relative to the design of the PFE/BNTX study. The COVE study doses patients on day 1 and day 29 and looks at the occurrence of COVID-19 at 14 days after the second dose and onwards. Since PFE is dosing patients on day 1 and day 21 and looking at COVID-19 cases from day 7 and onwards after the second dose, PFE has a two-week advantage over MRNA. Those tracking the rate of enrolment in MRNA's study note that enrolment is proceeding at about 4,000 participants per week and should be complete in the third week of September. Given that PFE seems to be enrolling patients at a similar rate, it seems likely that the two-week advantage should be enough for PFE/BNTX to report results before MRNA.

Figure 3: Primary outcomes of the COVE study. Source: Clinicaltrials.gov.

For AZN/Oxford, there was a discussion that if the company's 10,000-patient UK study demonstrates their vaccine (AZD1222) is effective, that emergency use authorisation is possible, despite the FDA having asked for studies in at least 30,000 people. Since AZN pretty strongly played down these suggestions, it isn't really clear if the name is really the front-runner, which leads me back to PFE and BioNTech. For example, on August 31, AZN announced it was planning to enroll more than 50,000 participants, including 30,000 in the US. It is possible, however, that data from the other 20,000 participants is announced prior to data from the 30,000 US patients being announced.

For clarity, the 30,000-patient US study is currently listed as "Not yet recruiting" although it was reported September 1 the trial was now enrolling. That trial doses patients twice, four weeks apart and looks at COVID-19 cases at 15 days and onward after the second dose.

Regarding the ex-US studies, the UK study is enrolling at 20 sites and has a targeted enrolment of 12,330 patients. That study does involve repeat dosing of the candidate COVID-19 vaccine four to six weeks apart in some arms of the study but doesn't specify when following dosing a look at COVID-19 cases compared to the control will be performed. The UK trial also includes an active comparator arm of two doses of a meningococcal vaccine, given 4-12 weeks apart. That could slow down any readout from the trial substantially. Further, a comparison of the ex-US studies shows some inconsistencies in the protocol. For example, there are differences in the second dose used in the UK and South African trials. Meanwhile, the Brazilian trial in 5,000 participants is only using a single dose.

It is worth mentioning that AZN has a 1,090-patient phase 1/2 study that could demonstrate efficacy but perhaps the confidence interval on that efficacy would be wider than the FDA wants (the lower bound would span below 30% efficacy; the FDA wants 50% efficacy with a lower bound above 30%). That trial won't be enough for approval anywhere in the world then but could signal that developing an effective COVID-19 vaccine is possible.

PFE/BNTX appear to be about two weeks ahead of MRNA in terms of timelines to report a result, due to the tighter dosing schedule (21 days vs. 29 days) and timelines for the endpoint (7 days vs. 14 days). Both trials appear to be enrolling at very similar rates. AZN/Oxford appears committed to not cutting any corners and a result in the US is further away. The timing of a result in AZN's ex-US studies seems harder to pin down and investors will need to wait for updates in that case.

Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

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Who Is Ahead In The COVID-19 Vaccine Race? - Seeking Alpha