5 FDA approval decisions to watch in the first quarter

Wednesday, January 5, 2022

Source: Biopharma Dive

The Food and Drug Administration's main drug review office approved 50 new medicines last year, its fourth highest total. Many were for cancer, continuing a trend of recent years, but there were notable new treatments cleared for high cholesterolHIV and, most controversially, Alzheimer's disease.

The busy pace looks set to continue in 2022, too, as the FDA works with industry to wrap up its latest agreement governing review timelines and user fees. Ahead of the agency this quarter are a number of notable approval decisions, five of which are outlined below.

Eli Lilly and Innovent's sintilimab in lung cancer

At face value, approval of yet another so-called checkpoint inhibitor — a type of cancer immunotherapy available for dozens of tumor types — wouldn't seem all that newsworthy. Eight of these drugs are already cleared, seven of which work similarly to Eli Lilly and Innovent Biologics' would-be immunotherapy sintilimab.

But the FDA's review of sintilimab, marketed in China as Tyvyt, is notable nonetheless, because it will show what the agency and its advisers think of an immunotherapy developed and exclusively tested in China.

Lilly acquired rights to Tyvyt from China's Innovent, and now aims to win U.S. approval without having to run a head-to-head study against an established checkpoint inhibitor. (Tyvyt was tested against chemotherapy alone in the trial supporting its application.)

Though not discussing Tyvyt specifically, Richard Pazdur and Julia Beaver, two of the FDA's top cancer drug officials, indicated in a recently published paper that such a study would "probably be required" in such a scenario. They also emphasized that the results of a clinical trial conducted overseas must be generalizable to the U.S. population.

The agency is holding an advisory meeting on Lilly's application on Feb. 10, and the implications are significant for the company and others, like Coherus Biosciences, that are looking to follow a similar path. What's more, Lilly has hinted it may undercut established checkpoint drugs on price, something that hasn't happened despite their widespread availability.

Bristol Myers Squibb's relatlimab in melanoma

Two types of checkpoint inhibitors are approved in the U.S. By mid-March, there could be a third as the Food and Drug Administration is set to decide on an immunotherapy developed by Bristol Myers.

The drug, known as relatlimab, is aimed at a different cellular target than earlier checkpoint inhibitors from Bristol Myers and companies like Merck, Roche and Regeneron. While those treatments work by blocking the proteins known as CTLA-4, PD-1 or PD-L1, relatlimab homes in on one called LAG-3.

The idea is similar, however. By blocking these proteins, immunotherapy helps cancer-fighting immune cells target and attack tumor cells.

An approval would be important for both the immunotherapy field, which has spent years seeking additional ways to unblind the immune system to cancer, and for Bristol Myers, which lost an early market advantage to Merck.

In clinical testing, combining relatlimab with Opdivo significantly reduced the risk of cancer progression over Opdivo alone in people whose melanoma had either spread or couldn't be surgically removed. The results were the first definitive proof that targeting LAG-3 can be beneficial, and the first time a treatment regimen had been shown to improve on Opdivo.

The FDA will make its decision by March 19.

Gilead's lenacapavir in HIV

For years, Gilead has maintained the world's leading business for HIV treatment. The first nine months of 2021 alone saw the company's line of medications for the virus generate about $11.8 billion in sales.

And yet, Gilead remains under constant pressure to innovate thanks to competition from deep-pocketed and powerful rivals like Merck, Johnson & Johnson and GlaxoSmithKline. On that front, a drug called lenacapavir has become important to Gilead's future.

Lenacapavir is designed to attach to the capsid — the shell that encases the virus' genetic information — and stop it from breaking apart, thereby impeding the HIV replication process.

Gilead has already scored positive clinical trial results showing that its drug helped suppress HIV in patients who had tried multiple other therapies but were no longer responding to them. Among the few dozen patients who've been evaluated thus far, around 80% had viral loads so low they were undetectable six months after starting treatment with lenacapavir and an optimized background regimen.

Based on those results, Gilead formally asked the FDA to approve lenacapavir last summer. A decision from the agency is expected by Feb. 28. If approved, it would be the first capsid inhibitor ever cleared for market, and the only HIV treatment option that's given every six months. (The review doesn't involve a different, injectable version of Gilead's drug, for which testing was recently halted.)

Analysts expect a title like that should translate to blockbuster sales over time. In fact, lenacapavir could deliver north of $1.1 billion to Gilead by 2030, according to consensus estimates compiled by the investment bank Mizuho Securities.

Akebia's vadadustat for anemia in chronic kidney disease

Not long ago, a group of pills known as HIF-PH inhibitors were supposed to be the next big thing in anemia care for people with failing kidneys. But their potential as convenient and safer alternatives to injectable drugs like Aranesp has dimmed.

A drug from Akebia Therapeutics called vadadustat, for example, appeared worse than Aranesp on a measure of heart safety in a Phase 3 trial the biotech reported in 2020. The FDA and its advisers then rejected FibroGen's roxadustat — already approved in several other countries — after its advisers flagged concerns about cardiovascular risk. FibroGen has since restructured, while shares of Akebia are trading at all-time lows.

HIF-PH blockers could still have a future in the U.S., however. In November, GlaxoSmithKline detailed positive Phase 3 results for its drug daprodustat, which is also approved overseas. And Akebia, despite its setbacks, has moved forward with an approval application, arguing the totality of its study results are good enough to secure regulatory clearance.

That belief will be put to the test this quarter. Though analysts have been skeptical the drug can win clearances for the broadest group of chronic kidney disease patients, some believe the FDA will approve it for those on dialysis, which still represents a sizable market.

The agency will make a decision by March 29.

AstraZeneca and Merck's Lynparza for early breast cancer

Lynparza, a type of cancer medicine known as a PARP inhibitor, has led the way for its class, winning approvals in multiple tumor types and becoming a multibillion dollar drug in the process. But its biggest impact yet could come soon, if the FDA approves it for early use in a particularly aggressive, hereditary form of breast cancer.

In a Phase 3 trial last year, Lynparza helped slow the return of HER2-negative tumors in women with an inherited mutation to the genes BRCA1 or BRCA2, which account for about 5% of all breast cancer cases. That benefit was observed when Lynparza was administered as an "adjuvant" treatment after surgery to remove a tumor and other standard drugs like chemotherapy. Treatment helped patients with both local as well as distant tumors, the latter of which can be particularly lethal.

Experts uninvolved with the study and interviewed by BioPharma Dive described the results as potentially practice-changing. But key questions remain, most notably how long Lynparza can extend lives and whether the drug's emergence will encourage BRCA testing. If cleared, Lynparza would also become the latest high-priced cancer medicine to move into an earlier setting, which are viewed as lucrative opportunities for drugmakers.

View All News »