Here is BP's view. Definitely more positive than many here....
Results show a single injection of MSB’s cells rexlemestrocel-L with Hyaluronic acid
(HA) carrier resulted in significant reduction in pain, which is also durable out to 24
months and also shows a significant reduction in opioid use in patients who were
opioid users at baseline, a very important outcome relevant for the US market. It also
found that the therapy worked best with superior pain reduction and outcomes in
patients who had the disease for a shorter duration (~5 years).
Key Highlights
Analyses was performed on total population and pre-specified subgroups of opioid
users at baseline and patients with chronic low back pain (CLBP) duration shorter or
longer than the median 68 months for the whole study population. Total evaluable
patients were 391 in the trial. Those with shorter duration of disease comprised 50% of
the trial population.
The trials primary endpoint was a composite of 50% improvement in pain and a 15 point
improvement in function at both 12 and 24 months with no surgical intervention. This is
structured more in line with medical devices rather than drug therapies that are
approved for chronic pain. Drug therapies trials are generally approved with pain
reduction as the primary endpoint, with most trials looking at data at 4 months.
Compared with saline, rexlemestrocel-L +HA achieved the composite endpoint with
highly significant p values in higher number of patients in both the pre-specified
subgroups of those having CLBP for less than 68 months (194 patients, p=0.04 and
0.06 respectively) and those who were baseline opioid users ( 168 patients, 32% vs.
12% saline, p=0.05). However, the composite outcomes of pain and function did not
reach statistical significance across the entire study.
Importantly on the key pain reduction endpoint,rexlemestrocel-L +HA treated patients
had a greater and statistically significant reduction vs. saline at both 12 months (-27.6
points reduction, p=0.014) and 24 months (-26.0 points reduction, p = 0.036).
The maximum reduction in the key pain endpoint was seen in patients with a shorter
duration of disease than 68 months. In this subgroup of 194 patients (50% of the total
evaluable population), rexlemestrocel-L +HA treated patients had a greater and highly
statistically significant reduction vs. saline at both 12 months (-36.9 points reduction, p
<0.0001) and 24 months (-36.5 points reduction, p <0.0001). Also noteworthy is 60% of
patients treated with rexlemestrocel-L +HA at 12 months and 54% at 24 months
achieved VAS < 20 target of minimal to no pain vs. saline (p=0.011 and p=0.036).
On the improved function and disability endpoint, patients in the shorter duration of
disease group also saw rexlemestrocel-L + HA showing statistically significant
improvement vs. saline at both 12 and 24 months, measured by either EQ-5D Index
(p=0.009 and p=0.020, respectively) or ODI (p=0.044 and p=0.059, respectively).
In opioid users, patients treated with rexlemestrocel-L + HA had a significantly greater
reduction in pain at all time-points (1, 3, 6, 12, 18 and 24 months) compared with saline
controls (p<0.05 for all timepoints). Also, by 24 months there was a 40% reduction in
opioid use in patients treated with rexlemestrocel-L + HA (p=0.03). On the other hand
a higher proportion of patients in the saline group saw an increase in their daily opioid
use over 24 months (50% vs. 13% at 24 months, p=0.0009). Treatment with
rexlemestrocel-L + HA resulted in nearly four times more opioid users achieving
50% reduction in pain as well as reduction in opioid use by 24 months than those
treated with saline(46% vs. 12%, p= 0.004).
There was no safety concerns, with the therapy safe and well tolerated over 24 months.
Tanushree Jain's view
We view this demonstration of efficacy in reducing pain with durability out to 2
years (and potentially to 3 years as seen in the previous Phase 2 trial) with a
single injection of rexlemestrocel-L as a major breakthrough not only for patients
living with the debilitating pain for whom currently available treatments provide
no relief, but also for the search for an effective non-opioid treatment for chronic
low back pain. Most importantly this comes without safety risks unlike current
therapies such as opioids and anti-inflammatory medications (NSAIDs) which are
associated with serious side effects with chronic use and also for other emerging class
of therapy such as the NGF growth inhibitors which are linked to joint problems,
sometimes serious enough to require joint replacement. We also note that the
composite endpoint of pain and function was successfully met in both the pre-specified
subgroups
We believe the data is strong enough for the company to be justified in pursuing
an accelerated approval pathway for the therapy in US both on grounds of being
an effective non-opioid pain relief drug, but also due to being opioid sparing (i.e.
reducing opioid use in patients), given the opioid crisis in US. Should FDA agree to an
accelerated pathway with condition of post approval confirmatory study, we could see
the therapy getting to the US market in 2HCY22. We expect MSB to meet with the FDA
in 1HCY21 to discuss path forward. We also expect that clarification of path forward
for the drug will be an important part of partnering discussions for the therapy for
the US market to come to a conclusion. Alternatively, in a conservative scenario with
another trial being required prior to approval, we believe this is likely to be funded by a
partner and see the therapy reaching US at a similar time frame to EU i.e. back end of
CY24/early CY25.
For EU, where opioid use is not a crisis, we believe MSB will continue on the
previous path with partner Grunenthal, with next steps being getting a Phase 3
trial protocol approved from EMA and triggering milestones to MSB potentially by
mid-CY21, followed by initiation of the trial before end of CY21. This is likely to
have a 12 month duration and potentially could get to EU market back end of CY24/
early CY25.
We are not making any changes to our forecasts at this stage, pending the release of
half yearly results from MSB later this month. We currently have a Buy (spec) and
Valuation of $5.10/sh on MSB, which remains unchanged at this point.
(20min delay)