Potential Blockbuster Drugs for 2021 – Alzheimer’s, Prostate Cancer and More
Clarivate published its annual “Drugs to Watch” list, and cited four drugs that it expects to be blockbusters—projected to bring in $1 billion in sales annually. There is a possible snag, though—one may struggle to get approved.
Biogen and Eisai’s Aducanumab for Alzheimer’s Disease
Earlier this year, the U.S. Food and Drug Administration (FDA) extended the review period for Biogen and Eisai’s Biologic License Application (BLA) for aducanumab for Alzheimer’s disease. The drug has been fraught with controversy—and unexpected hopes. The decision by the FDA on the drug application was expected on March 7, but is now delayed until June 7, 2021.
In March 2019, Biogen and Tokyo-based Eisai, announced they were discontinuing the global Phase III clinical trials, ENGAGE and EMERGE, of aducanumab in patients with mild cognitive impairment for Alzheimer’s and mild Alzheimer’s dementia. They were also discontinuing the EVOLVE Phase II trial and the long-term extension PRIME Phase Ib trial. An independent data monitoring committee indicated they were unlikely to hit their primary endpoint.
It appeared to be the final nail in the amyloid theory of Alzheimer’s disease. Aducanumab is an antibody targeting beta-amyloid, one of the proteins that accumulates in the brains of Alzheimer’s patients.
But in October 2019, the two companies announced plans to pursue regulatory approval for the drug. It turned out, the Phase III EMERGE trial met its primary endpoint, showing a significant decrease in clinical decline. Biogen presented the findings in the final data analysis in a December conference, and although there was still some skepticism about the overall data, it did appear to be enough to file for a BLA and the company planned to do so in the second quarter of 2020.
What they presented was that the Phase III EMERGE trial met its primary endpoint, showing a significant decrease in clinical decline. Biogen said the data from a subset of patients that received a high enough dose of the drug had significant benefits on measures of cognition and function, including memory, orientation, and language, as well as benefits on activities of daily living.
Although many had issues with some of the data, which was very complex, the companies felt they had a strong enough case to submit it to the FDA and were expected to do so this spring.
Then, in April 2020, they announced that although the company had begun to submit parts of the BLA, they did not expect to complete it until the third quarter of this year.
The submission was completed in August 2020 with ongoing collaboration with the FDA and include data from the Phase III EMERGE and ENGAGE trials, as well as the Phase Ib PRIME study. Biogen has also requested Priority Review.
In November 2020, the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee slammed the drug submission, voting 1 yes, 8 no and 2 uncertain on the question, “Does Study 302 (EMERGE), viewed independently and without regard for Study 301 (ENGAGE), provide strong evidence that supports the effectiveness of aducanumab for the treatment of Alzheimer’s disease?” It also voted 0 yes, 7 no and 4 uncertain on whether Study 103 (PRIME) supported the effectiveness of the drug. Again and again, the committee voted against the drug.
Apparently the newest delay is related to the FDA requesting additional analyses and clinical data. Biogen complied, and the FDA considered it a Major Amendment to the application, thus requiring additional review time.
If approved, and that seems like a big “if,” the Clarivate analysts describe it as a “monumental opportunity to radically change patient care and transform the market.”
UCB’s Bimekizumab For Plaque Psoriasis
On September 22, 2020, UCB, based in Brussels, Belgium, announced that the FDA and European Medicines Agency (EMA) accepted the company’s BLA and Marketing Authorization Application (MAA), respectively, for bimekizumab for adults with moderate to severe plaque psoriasis. The submissions were based on positive Phase III data readouts. All met their primary endpoints, demonstrated that patients receiving the drug achieved superior skin clearance at week 16 compared to those who received placebo and those who received AbbVie’s Humira (adalimumab).
The drug is a humanized monoclonal IgG1 antibody that selectively inhibits both IL-17A and IL17F, two cytokines that drive inflammation. Probably more importantly, given Humira’s ubiquity, bimekizumab appears to have significantly fewer side effects. The Clarivate team wrote, “While bimekizumab is a late-class entrant providing incremental improvement over existing treatment options, it is expected to have best-in-class efficacy and fewer serious side effects.”
Takeda and Myovant’s Relugolix for Prostate Cancer
Relugolix is an oral drug to treat prostate cancer. But in addition to that, it is being developed for endometriosis and uterine fibroids in women. The Clarivate analysts believe it’s these three shots on goal that increase the drug’s chances of success. The oral formulation also has advantages over injectable GnRH agonist competitors.
On December 18, 2020, the FDA approved the drug, which was developed by Myovant Sciences, under the name Orgovyx/Relumina, for adults with advanced prostate cancer. It is the first oral gonadotropin-releasing hormone (GnRH) receptor antagonist.
In May 2018, Takeda and ASKA Pharmaceutical entered into a licensing deal, granting ASKA exclusive commercialization rights for the drug for uterine fibroids and exclusive development and commercialization rights for endometriosis for Japan. Takeda holds commercial rights in Japan and parts of Asia. Myovant Sciences holds rights in other regions. Myovant Sciences was formed by Takeda and Roivant Sciences in June 2016.
Bayer and Merck’s Vericiguat for Chronic Heart Failure
On January 20, 2021, the FDA approved Verquvo (vericiguat) to reduce the risk of cardiovascular death and heart failure hospitalization following a hospitalization for heart failure or need for outpatient intravenous (IV) diuretics in adults with symptomatic chronic heart failure and ejection fraction less than 45%. The approval was based on data from the pivotal Phase III VICTORIA trial. The drug is jointly developed by Merck and Bayer AG.
Clarivate noted, “Vericiguat’s novel mechanism of action should result in its acceptance as an add-on therapy to existing treatments. It will likely find its niche among high-risk HFrEF patients, become a welcome addition to the treatment armamentarium and expand their treatment options.”