On November 11, 2019 USA News Group – As the global oncology drug market is projected to grow at a rate of 7.6% CAGR to hit $176.5 billion by 2025, there’s a growing interest within the big pharma sector to tap into the power of viruses to fight cancer (Press release, Oncolytics Biotech, NOV 11, 2019, View Source [SID1234550880]). It’s estimated that the therapeutic cancer vaccine market alone will reach more than $15 billion by 2025. Dubbed ‘oncolytic viruses’ these treatments utilize all types of viruses to encourage the patient’s immune system to respond and attack cancer cells with heightened efficacy. It’s been seen that a variety of majors including Amgen Inc. (NASDAQ:AMGN), Merck & Co. (NYSE: MRK), AbbVie Inc. (NYSE:ABBV), and Bristol-Myers Squibb (NYSE:BMY) are looking at a variety of oncolytic virus developers, such as Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC).
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Innovators like development stage Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) are drawing interest from major partners for developing their own immuno-oncology virus. The companuy’s proprietary reovirus, marketed as pelareorep, is currently being studied for potential combination with Opdivo from Bristol-Myers Squibb Company and Keytruda from Merck & Co., Inc.
In 2018, both Opdivo and Keytruda are multi-billion dollar products—Opdivo sales were $6.7 billion, while Keytruda sales were $7.2 billion. Pelareorep is also being studied for potential combinations with Merck/Pfizer’s paclitaxel and Bavencio (which sold $75.5 million in 2018), and Roche’s Tecentriq (which had sales of $766 million in 2018).
Now with the Opdivo and Keytruda developments, it’s worth noting that Bristol-Myers Squibb and Merck are no strangers to the oncolytic virus scene. Both companies have made significant investments in the oncolytics virus sector in recent years.
MAJORS MAKING 9-DIGIT ONCOLYTIC VIRUS INVESTMENTS
In 2015, Amgen Inc. became the first company to win approval for such a treatment, when the FDA approved the therapy T-VEC (or Imlygic) to treat metastatic melanoma that cannot be surgically removed. The approval was based on the results of a multicenter phase 3 clinical trial of patients with metastatic melanoma lesions in the skin and lymph nodes.
Bristol-Myers Squibb followed up this approval, by entering a partnership in 2016 with PsiOxus involving its lead asset Adenovirus, which was in phase 1. The transaction involved a $50 million payment up front, with up to $886 million in milestone payments and royalties at stake. The first milestone payment was earned the following year when it achieved approval for its Clinical Trial Application.
Merck has also been active, including the acquisition of Viralytics for its lead asset Coxsackievirus which was in phase 1b at the time of acquisition, and another immunotherapy partnership with Vyriad (and lab partner Pfizer), involving its lead drug candidate Voyager-V1.
Merck acquired the virus-based cancer drug firm Viralytics for $394 million in 2018, at a premium price of 160% to the average stock price over the previous month. Viralytics’s leading experimental product at the time of acquisition was Cavatak, which uses a proprietary formulation of a common cold virus, and was in the process of being studied in multiple Phase I and Phase II clinical trials.
In 2017, AbbVie Inc. partnered with another Canadian drug developer Turnstone Biologics. The deal gives AbbVie the exclusive right to license up to three of Turnstone Biologics’ immunotherapy treatments for commercial purposes. Terms of the deal, however, are not publicly available.
PELAREOREP’S ONGOING PROGRESS
Pelareorep from Oncolytics Biotech Inc. (ONCY – ONC.TO) selectively infects tumor cells, leading to the creation of inflamed tumors. The body’s ability to target the inflamed tumors is heightened, leading to the creation of tumor reactive T cells. In turn, pelareorep expands existing T cell clones priming the immune system for checkpoint blockade. To date, the drug has synergized with all checkpoint inhibitor combinations tested.
So far, based on the final advice from the FDA following their EOP2 meeting, the company’s been granted Special Protocol Assessment (SPA). It’s been recommended that identification of biomarker should be done before Phase III. Confirmation of a single phase 3 study is required for approval.
Through a partnership with Northwestern Medicine’s Feinberg School of Medicine, and Merck & Co., Oncolytics is studying pelareorep’s potential with Merck’s Keytruda in targeting metastatic pancreatic cancer. The phase 2 study incorporates up to 30 patients.
In another partnership involving Keytruda, Oncolytics is pairing with Merck and Keck Medicine of USC to study a combination efficacy involving multiple myeloma. The phase 2 study involves 22 patients, and will incorporate existing safety data in combination with Keytruda.
For a combination with Opdivo, Oncolytics is also targeting multiple myeloma, by collaborating with Bristol-Myers Squibb and Emory University, in a phase 1 study. The study involves 40 to 50 patients, and so far at the top dose, there has been a 100% response rate.
"Having worked with pelareorep in multiple myeloma and understanding its ability to act as a potentiator of checkpoint blockade, I’m very excited to work with the Oncolytics team on this study," said Dr. Craig Hofmeister, Associate Professor, Department of Hematology and Medical Oncology Emory University School of Medicine. "Pelareorep has proven its ability to create an inflamed phenotype and its potential for upregulation of PD-1 on tumor-infiltrating lymphocytes. My hope is this study leads not only to an effective combination dosing schedule but provides quantitative data describing the expression of PD-1, along with correlative studies that reveal the roles of both immune-mediated and direct cytotoxic myeloma cell killing."
To date, pelareorep has been involved with 1,100 patients treated, of which over 900 were administered intravenously. To date, no maximum tolerated dose (MTD) has been reached.
In terms of manufacturing the product, Oncolytics Biotech Inc. (NASDAQ:ONCY) (TSX:ONC) has established cost-effective contract manufacturing. The final formulation was produced at 100 liter-scale under cGMP—which is more than 50,000 standard doses per production run.
Oncolytics has established a commercial scale manufacturing agreement with SAFC (part of Merck Millipore Sigma). When stored frozen, the liquid formulation is stable for at least five years (with stability testing ongoing).
Pelareorep has been given biosafety level 2 classification, thus requiring no specialized handling requirements. Cost of Goods (COGS) are in line with those of other products made via vaccine manufacturing process.
Oncolytics has 398 patents issued worldwide, including 48 US and 21 Canadian, with over 21 more pending applications worldwide. The reovirus issued patent claims cover compositions of matter comprising reovirus (through 2028 and extendable to 2033), and all pharmaceutical uses of it.
THE ONCOLYTIC VIRUS SCENE AHEAD
Merck & Co. (NYSE:MRK) made a big splash in the oncolytic virus scene when it bought the Australian biotech firm Viralytics for $394 million. The massive price paid signaled that Viralytics was an asset that Merck just had to own.
This was similar to the size of payment that Amgen Inc. (NASDAQ:AMGN) made, when it paid $424 million for Biovex in 2011. Given that Amgen’s T-VEC was the first oncolytic virus to receive FDA approval, it’s realistic to believe that they’re not done solidifying their position in the space. T-VEC is a genetically engineered oncolytic herpes virus, that’s injected into skin tumors, resulting in shrinkage or complete remission of tumors.
AbbVie Inc. (NYSE:ABBV) tipped its hand towards an interest in oncolytics viruses, when it secured an option on three oncolytic viral immunotherapies from Turnstone Biologics. The deal gives AbbVie the chance to add Turnstone’s lead MAGEA3 candidate to its pipeline once data from the two ongoing phase 1/2 trials are available.
While Bristol-Myers Squibb (NYSE:BMY) continues to work with Oncolytics Biotech Inc. (NASDAQ:ONCY) (TSX:ONC) for a combination with Opdivo, the major invested heavily in a partnership with PsiOxus for roughly $900 million. Together, they are developing an oncolytic adenovirus, which has already earned a $15 million milestone payment for PsiOxus.