Mesoblast Soars 10% on ASX, US FDA Set To Review Remestemcel-L Data

Summary

• The Oncologic Drugs Advisory Committee (ODAC) of the US FDA is scheduled to meet on 13 August 2020 for the approval of Mesoblast’s RYONCIL™ (remestemcel-L).
• Remestemcel-L, an investigational therapy administered via a series of intravenous infusions, is considered to hold immunomodulatory properties for counteracting the inflammatory processes that are associated with SR-aGVHD.
• There exists only one approved treatment for SR-aGVHD, while no approved treatment is present for children under 12 years old, outside Japan.
• Mesoblast is also evaluating remestemcel-L in COVID-19 ARDS through its Randomized Controlled Phase 3 Trial.

The world leader in developing allogeneic cellular medicines, Mesoblast Limited (ASX:MSB) appears all in rage amongst the investors with the announcement of review date scheduled by the US Food and Drug Administration (FDA) advisory committee for Mesoblast’s Remestemcel-L in pediatric steroid-refractory acute graft versus host disease (SR-aGVHD).

Following the significant announcement, MSB stock edged up by 10.5% on 21 July 2020 to close at AUD 3.7 per share. The stock in the past three-months has generated remarkable 65% return.

The Oncologic Drugs Advisory Committee (ODAC) of the United States Food and Drug Administration (FDA) is arranged to meet on 13 August 2020 concerning the approval of RYONCIL™ (remestemcel-L). The Committee would review data supporting Mesoblast’s Biologics License Application (BLA) before it authorises remestemcel-L as the treatment of SR-aGVHD in children.

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About RYONCIL^TM (Remestemcel-L)

Application and Opportunities

Mesoblast is working towards the treatment of a life-threatening complication aGVHD, which has been seen to occur in approximately 50% of patients who receive allogeneic bone marrow transplants. Meanwhile, the company also reports that the mortality rate of SR-aGVHD is as high as 90% along with significant extended hospital stay costs.

Besides, there exists minimal treatment options as there is only one approved treatment for SR-aGVHD and no approved treatment for children under 12 years old, outside Japan.

The company’s lead product candidate, Remestemcel-L is an investigational therapy, which comprises of culture-expanded mesenchymal stem cells taken from the bone marrow of an unrelated donor.

The lead candidate administered via a series of intravenous infusions is considered to hold immunomodulatory properties for counteracting the inflammatory processes that are associated with SR-aGVHD.

It is done by down-regulating pro-inflammatory cytokines production while increasing anti-inflammatory cytokines production, along with enabling recruitment of naturally occurring anti-inflammatory cells to involved tissues.

Mechanism of Action. Source: MSB ASX Update

Mesoblast’s Advancements concerning RYONCIL^TM

Mesoblast conducted a comparative analysis between Mesoblast’s open-label Phase 3 study and contemporaneous controls receiving institutional standard of care. RYONCIL™ was found to demonstrate efficacy and survival benefit in children with SR-aGVHD that includes those that suffered most severe grades of the disease.

Meanwhile, the FDA BLA filing is supported by three study results which used RYONCIL™ in children and adults with SR-aGVHD. It includes:

• In an expanded access program, RYONCIL™ was used as salvage therapy in 241 children with SR-aGVHD (80% Grade C/D) who failed institutional standard of care.
• In Mesoblast’s open-label Phase 3 trial, RYONCIL™ was used as first-line therapy in 55 children with SR-aGVHD (89% Grade C/D).
• In a randomised controlled Phase 3 trial, RYONCIL™ was used as first-line therapy in 260 adults and children with SR-aGVHD.

BLA filing for RYONCIL™ for priority review for treating SR-aGVHD in children was accepted by the US FDA.

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FDA Review Details

RYONCIL™ by Mesoblast is under Priority Review by the FDA with an action date of 30 September 2020, under the Prescription Drug User Fee Act (PDUFA). As of now, no FDA-approved treatment is available in the United States for children under the age of 12 with SR-aGVHD, which is a potentially life-endangering complication of an allogeneic bone marrow transplant for blood cancer.

Oncologic Drugs Advisory Committee (ODAC) is an independent panel of experts which on the basis of potential issues highlighted by the FDA provides advice and appropriate recommendations to the FDA. The ODAC notably reviews the efficacy and safety of marketed and investigational products for utilising in cancer treatment.

Although FDA would consider the panel’s recommendation, the final decision regarding product approval is solely made by the FDA, with the panel’s recommendations remaining non-binding.

Kalkine Image (Data Source: MSB ASX Update)

Remestemcel-L for COVID-19 ARDS

Rationality for treating COVID-19

The high mortality caused by COVID-19 respiratory virus is due to a severe inflammatory condition of the lungs known as acute respiratory disease syndrome (ARDS), resulting from cytokine storm in lungs of COVID-19 patients, becoming the primary cause of death.

A compelling rationale is made for evaluating remestemcel-L in COVID-19 ARDS owing to the extensive safety data of remestemcel-L and its anti-inflammatory effects in aGVHD. Administering remestemcel-L via intravenous delivery leads to selective migration to the lungs, which makes inflammatory lung disease an ideal target for the therapy.

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Study Progress

Pilot data from Emergency IND delivers further rationale for conducting Randomized Controlled Phase 3 Trial of Remestemcel-L in COVID-19 ARDS. Notably, out of 12 patients (moderate or severe ARDS) at Mt. Sinai Hospital who received two infusions of remestemcel-L, nine patients came off ventilator support at a median of 10 days and discharged from hospitals. The results contradict with 9% extubating COVID-19 patients and survival rate of 12% during the same period in two major NY hospital networks.

For assessing the safety and efficacy of remestemcel-L versus standard of care in COVID-19 ARDS patients on a ventilator, Mesoblast has planned to conduct trials at up to 30 major teaching hospitals across North America. The company anticipates the completion of recruitment within three to four months, while it has planned interim analysis which could result in stopping the trial early for efficacy or futility.

Moving Forward

Mesoblast’s Biologics License Application is seeking approval of its product candidate RYONCIL™ (remestemcel-L) for SR-aGVHD, which if approved is expected to launch in the US in 2020.

The company is also developing Remestemcel-L for other inflammatory diseases concerning moderate to severe acute respiratory distress syndrome in children and adults.

Phase 3 trials for its product candidates for advanced heart failure and chronic low back pain is being completed by Mesoblast.

Mesoblast’s licensees have commercialised two products in Japan, and Europe and the Company for certain Phase 3 assets have established commercial partnerships in Europe and China.