Welcome to a new issue of The Biopharma Report!
GSK’s Respiratory Syncytial Virus Older Adult Vaccine Candidate Granted Priority Review by US FDA
That was one busy week in terms of RSV. A few quarters ago it wasn’t necessarily clear who would emerge victorious from the RSV race - but lately the fog of war has started to dissipate.
Pfizer had announced a few days ago that it was halting the trial for its RSV vaccine candidate in the maternal population because it hit one of the two primary endpoints - reduction in severe MA-LRTI (severe medically attended lower respiratory tract illness) - required for regulatory filing. The company had also announced positive results for its adult vaccine program back in August. Pfizer is expected to file for approval by end of year for both populations.
GSK announcing that the FDA had granted Priority Review to its vaccine in the adult population signals that the British company probably has a leg up on Pfizer. While GSK’s RSV vaccine candidate is one step closer to FDA approval in adults aged 60 years and older, the maternal vaccine program seems to be less promising - for now at least. Since GSK voluntarily halted enrollment and administration of the vaccine in the maternal population in February on safety grounds, it has been awfully quiet about the status of the maternal program - but it’s likely that they are still going through the safety data in order to decide if it’s worth it to continue clinical development.
The adult market is obviously more attractive than the maternal one (roughly double the size). But will GSK be at disadvantage because it may potentially only have a vaccine in one population? Will providers and payors in different geographies prefer to deal with Pfizer out of logistic and economic convenience because they would have a vaccine that is approved in both populations?
This would obviously depend on a lot of variables, but if the FDA approves GSK’s candidate in May 2023, the first-mover advantage would significantly hurt Pfizer’s commercial potential in this adult RSV market.
Generally speaking, there are no considerable differences in terms of efficacy when we compare the Pfizer RSV vaccine candidate to the GSK one in the adult population - but it seems that the Pfizer jab has a better tolerability profile than its GSK counterpart. This is definitely something that Pfizer will focus on in terms of marketing in order to differentiate its vaccine.
But the Pfizer data is not perfect. Although one of the primary endpoints required to file for approval was hit in the maternal trial, the other endpoint - reduction in MA-LRTI (medically attended lower respiratory tract illness) - wasn’t. The difference between both endpoints is the severity of the disease observed in patients. This could be bad news for Pfizer.
GSK and Pfizer are not the only players in the RSV space.
Sanofi and AstraZeneca have developed Beyfortus (nirsevimab), a single-dose preventive antibody (not a vaccine per se) for infants that was just approved by the EMA. And unlike Pfizer’s asset, data from Beyfortus’ pivotal trial show a statistically significant reduction in MA-LRTI. It’s hard to say how this will impact the commercial potential of Pfizer’s vaccine - especially given that the source of the Pfizer data are only press releases that do not provide in-depth data and information on the methodology.
AstraZeneca and Sanofi have already filed for approval with the FDA and could potentially launch Beyfortus in the US in Q3/Q4’23. It is worth noting that Sanofi execs mentioned that Beyfortus will be priced like a vaccine - meaning that it will not be as cost-prohibitive as Synagis, the antibody that was approved 20 years ago for the prevention of severe disease caused by RSV. Synagis will obviously be displaced (and cannibalized) as new more affordable alternatives enter the market
Wonder-pharma Moderna is developing an mRNA-based vaccine that targets RSV, SARS-CoV-2 virus, and the influenza virus (sounds like science fiction) as well as another jab that exclusively targets RSV. And last but not least, J&J and Bavarian Nordic are also developing RSV vaccines.
The RSV vaccine race is probably one of the most intense pharma rivalries in years - but who will emerge victorious?
Alkermes Announces Intent to Separate Oncology Business
The split makes complete sense - and has been due for some time. As Alkermes’ lead oncology IL-2 immunotherapy asset nemvaleukin alfa progresses through clinical development, it will have to eat up more and more of Alkermes’ limited resources - resources that would be put to better use in their CNS franchise and more specifically in Lybalvi. Alkermes has expertise and experience in the CNS space - not in oncology - so it makes sense to trim the “fat” and focus on its core business. Hopefully that will get the stock moving.
Another factor that makes the split more strategic for Alkermes is that the IL-2 immunotherapy space has been absolutely brutal lately. Data from ESMO back in September showed that BMS and Nektar Therapeutics’ IL-2 drug bempegaldesleukin actually made Opdivo less effective when the combo was given to melanoma patients. This comes after the bempeg-Opdivo combo led to disappointing outcomes in renal cell carcinoma.
Sanofi’s own IL-2 asset SAR444245 - part of the $2.5B acquisition of Synthorx - has also had a rough patch. Sanofi recently announced that it was halting its phase 2 trials due to disappointing efficacy and that it was starting a new phase 1/2 program with more intense dosing regimens. Sanofi also mentioned “external data” to justify killing the phase 2 trials - which is funny given that not so long ago the French pharma was touting the BMS/Nektar disappointing IL-2 data as good news for SAR444245.
As much as I admire Sanofi CEO Paul Hudson for off-loading assets that are not promising, I do think that more can be done in terms of scientific due diligence before rushing into M&A - but that’s a discussion for another time. It is worth noting though that back in August Sanofi signed a deal with Chinese player Innovent Biologics for the development of SAR444245 in China.
What the future reserves for nemvaleukin alfa and IL-2 immunotherapy drugs in general is not clear but I wouldn’t get my hopes up - yet. One thing that baffles me is why Alkermes - a CNS-focused company with no real oncology track record - decided to develop nemvaleukin alfa without enlisting help from large pharmas. Hopefully the new company will try and strike a partnership with an established oncology player to maximize the likelihood of success - but finding a partner willing to open its wallet for the IL-2 asset won’t be a walk in the park.
Lybalvi is currently Alkermes’ raison d'être. It wasn’t an easy path to market. Alkermes was slapped with a CRL back in 2020 over concerns with the manufacturing facility. The drug eventually got approved in 2021, but there have always been concerns regarding how samidorphan - one of the active ingredients of the med - can affect patients on opioids. Samidorphan bascially reduces the weight gain caused by olanzapine - the other active ingredient in Lybalvi. So basically Lybalvi is olanzapine minus the weight gain (plus possible interactions with patients on opioids). Lybalvi is to a degree competing with olanzapine which has the advantage of being a dirt-cheap generic drug.
Alkermes leveraged the relationships and market position it built with its antipsychotic Aristada to optimize the launch and commercialization of Lybalvi. Marketing in the schizophrenia space is notoriously hard, but Alkermes played its cards well in terms of messaging and focused on patients that were on olanzapine and who were complaining of weight gain. One challenge that Alkermes initially faced - and overcame - is that the pandemic generally made it harder for patients to switch drugs because they couldn’t see their physician.
Prescription volumes have been steadily increasing lately with physicians becoming more comfortable with the drug. Lybalvi has certainly more room to grow, and now with Alkermes more focused than ever on CNS; I have high expectations.
DISCLAIMER: This is for informational purposes only, you should not construe any such information or other material as legal, tax, investment, financial, or other advice.
DISCLOSURE: I have no business relationships with any company that is mentioned in this article.