With US still the reigning global champion in biotech innovation, the dynamic and vibrant biopharma ecosystem in the world’s largest healthcare market continues to churn out ground-breaking innovations with companies aspiring to follow in the footsteps of success stories like Regeneron, Celgene, and Amgen. Once US biotechs achieve the significant milestone of receiving their first US FDA approval, however, they must contend with a pressing question: what to do with the drug in the rest of the world?


As part of our ongoing US Healthcare and Life Sciences Review publication, we had the opportunity to discuss this topic with the CEOs of two of the most novel US biotech companies operating today: Karyopharm Therapeutics, a pioneer in nuclear export regulation, and Ionis Pharmaceuticals, a pioneer in RNA therapeutics with their proprietary antisense drug discovery platform. Karyopharm’s first drug XPOVIO® has been approved by the FDA since July 2019, while Ionis Pharma has two US approvals and one EU approval.


In his interview with PharmaBoardroom, Karyopharm founder and CEO Dr Michael G. Kauffman enthused, “we have been pleased with XPOVIO®’s performance so far. Following our July 2019 approval, many industry observers actually thought our drug would struggle to perform. The analyst expectation for the first quarter was USD 2 million. Our actual sales were USD 12 million!” Despite COVID-19’s negative impact on sales in Q1 2020, Q2 sales recovered well and Kauffman was confident that XPOVIO® would ultimately see solid figures for 2020, pointing out that “Wall Street expectations for 2020 is USD 80 million and then more than double that – USD 170 million – for 2021.”


Any collaboration between a small company and a Big Pharma player will always be heavily weighted towards the latter since smaller companies cannot compete in terms of funding and resources

Michael Kauffman, Karyopharm


For the US market, Karyopharm decided to commercialize XPOVIO® themselves for a number of reasons. Kauffman, who had held leadership positions in four other biotech companies prior to establishing Karyopharm with his wife – current Karyopharm President and CSO Dr Sharon Shacham – in 2008, revealed, “having worked with a number of biotech companies and dealt with partnerships and collaboration agreements with Big Pharma companies, while Big Pharma companies do many things well, even in co-promotion agreements, I think there is never a true partnership. Any collaboration between a small company and a Big Pharma player will always be heavily weighted towards the latter since smaller companies cannot compete in terms of funding and resources.” Despite acknowledging that a Big Pharma partnership would have brought more financial stability, he was confident that Karyopharm could do it alone.


The breakthrough nature of the company’s nuclear export regulation was also an important consideration. “XPOVIO®’s first indication is for relapsed refractory multiple myeloma (RRMM), and I have extensive experience with multiple myeloma drugs and more generally, the US market. [At the same time] XPOVIO® is a very innovative oral product with high potency and high differentiation from other multiple myeloma drugs. We wanted to work directly with patient groups and physicians to properly educate them on the drug.” Ultimately, Karyopharm’s Board and leadership team agreed: “Commercialising the drug ourselves in the US would ensure that we retain the innovation and the nimbleness within the US organisation.”


On the other hand, Ionis Pharmaceuticals CEO Brett Monia has a slightly different perspective on the best commercial strategy for the company in the domestic market. In his interview with PharmaBoardroom he shared, “over the past few years, we have developed many strategic partnerships with large pharma companies like Roche, AstraZeneca, Novartis, Pfizer and Biogen.” This has fundamentally been driven by the priority to “commercialize our products most efficiently so that they reach as many patients as quickly as possible”. As Monia emphasized, “our partners – the likes of Roche, AstraZeneca, Novartis, etc. – have the global muscle to launch our products in the largest markets like the US, EU, Japan, and China.”


Our partners – the likes of Roche, AstraZeneca, Novartis, etc. – have the global muscle to launch our products in the largest markets like the US, EU, Japan, and China

Brett Monia, Ionis


Ionis Pharma has developed three approved products: the spinal muscular atrophy (SMA) drug, SPINRAZA®, approved in a number of markets now including the US, EU, Japan, Canada and Brazil, to which Biogen holds global rights; TEGSEDI®, approved in the US and marketed by Ionis subsidiary Akcea Therapeutics; and WAYLIVRA®, approved in the EU and also marketed by Ionis subsidiary Akcea Therapeutics.


For this reason, Ionis plans to continue pursuing this out-licensing and partnership strategy for their current pipeline, which currently boasts, among others, two large franchises in neurological diseases as well as cardiovascular and metabolic diseases, with over ten drugs in each. For instance, in 2019, Monia recalled, “we concluded such a global exclusive licensing agreement for a Phase II drug with Pfizer through our majority-owned affiliate, Akcea Therapeutics, for certain cardiovascular and metabolic indications. We will continue to partner strategically with Big Pharma players for our assets in broad indications.”


However, Monia does have plans to transform Ionis into a commercial organization, anticipating, “now that Ionis is in such a strong position in terms of our robust pipeline, validated platform technology, strategic partnerships,# and finances, one of my priorities over the next few years is to build our own pipeline and create our own commercial capabilities. This will be our own portfolio, focus[ed] on rare diseases.” However, he cautioned, this would have to be executed judiciously. “as we are not a Roche-sized company, we want to manage our growth appropriately. We want to grow in proportion with our culture and our science. We are committed to our cutting-edge science and culture of innovation, and our commercial activities will not compromise that commitment.”


Through their US domestic strategies differed, both biopharma CEOs clearly concur on the importance of the partnership approach when it comes to global markets.


Karyopharm CEO Kauffman has outlined a tri-pronged global strategy. Beyond the US, “the second region we have defined is the Far East, specifically the markets of Greater China, South Korea, ASEAN countries, Australia and New Zealand. Here, we recognised that a small company like Karyopharm cannot commercialise a drug efficiently or expeditiously, which is why we are working with Chinese biopharma player Antengene.” The Chinese biotech, established in late-2017, is led by Dr Jay Mei, who, while working at Celgene from 2008 to 2017, was heavily involved with the launch and commercialisation of Celgene’s multiple myeloma drug, Revlimid®, in China. Already, Kauffman highlighted, “they have done a remarkable job of advancing XPOVIO® in terms of clinical and regulatory approvals, and we expect to file an NDA with the China NMPA very soon.”


The final prong for Karyopharm involves primarily Europe and Japan, along with the rest of the world. Here, the company is still negotiating with potential partners, and as Kauffman explained, “though Europe remains an important region for us, as most of the patients we have recruited in clinical trials are actually in Europe, we do not plan to establish a direct presence in these geographies for now. In any case, COVID-19 has made that prospect even less feasible than previously evaluated.” With their preference for “a strong European partner who will see XPOVIO® as a very important and strategic asset within their portfolio”, Karyopharm is speaking mostly to European mid-caps and smaller companies, not multinationals, who, in any case, Kauffman mentioned wryly, “all wanted a piece of the US”.