5 FDA approval decisions to watch in Q1

 While the COVID-19 pandemic has disrupted the Food and Drug Administration's review of new drugs, the agency's main office still managed to approve 53 medicines last year, near a record high set in 2018. 

That total doesn't include some biologic drugs products, nor does it count the emergency use authorizations for two coronavirus vaccines issued by the FDA last month — reviews that consumed much of regulator's time and attention. 

Coronavirus vaccines will still be a major focus in 2021, with several others near completion of late-stage testing. But the agency has a full plate of drug reviews, too, and will soon make one of the most important decisions in its recent history: whether to approve Biogen's controversial Alzheimer's treatment aducanumab. 

Decisions on a heart failure drug, a new Duchenne muscular dystrophy medicine and a cancer cell therapy are expected before the end of March as well. 

The following five drugs are listed in order of the currently scheduled date by which the FDA has agreed to make a decision on approval.

Merck & Co.'s vericiguat for heart failure

In spite of an array of medicines, the prognosis for heart failure patients remains poor, with one estimate putting median survival at just over two years following hospitalization. Nonetheless, few new drugs have been shown to improve on existing regimens, with Novartis' Entresto, approved in 2015, a notable exception. 

Merck and Bayer, though, have submitted vericiguat for use in people whose hearts have weakened to the point where they can pump no more than 45% of the blood in the left ventricle, compared to 55% or more in a healthy heart. A pivotal trial showed that, when added to normal treatment for recently hospitalized patients, vericiguat can reduce the risk of another hospitalization or death by 10%. When the data was examined closely, however, the drug did not have any effect on cardiovascular death.

The FDA is expected to decide on approval by Jan. 20.

Entresto is already approved for these patients, but because only 15% of the patients in the vericiguat trial also received Novartis' drug, physicians may need more data to support using the drugs in combination.

Cowen analyst Steve Scala, commenting on the vericiguat results when they were released last March, argued the drug will likely be used in only the most severe patients, a small share of the estimated 3 million people who would be eligible.

Sarepta's casimersen for Duchenne muscular dystrophy

Casimersen has so far avoided the controversy that accompanied FDA approvals of Sarepta's first two drugs, Exondys 51 and Vyondys 53.

By now, FDA reviewers should be familiar with Sarepta's approach of using a drug to prevent translation of a disease-causing genetic mutation, which is how Exondys and Vyondys work to treat Duchenne. In clinical studies, casimersen stimulated greater production of a key muscle-building protein called dystrophin, levels of which reached about 2% of normal after treatment compared with less than 1% of normal at baseline.

Exondys and Vyondys were approved on similarly modest benefits, so unless the FDA review turns up a previously unidentified safety issue, casimersen looks likely to gain approval. The FDA didn't convene an advisory committee to review the drug, which will be sold as Amondys 45 if cleared. 

Each drug is targeted to specific, genetically defined subsets of Duchenne patients who are likely to benefit from treatment. An estimated 8% of Duchenne patients would be eligible for casimersen, according to Sarepta. 

A decision on casimersen, which is expected by Feb. 25, is one of two big early-year catalysts for Sarepta. Long-term data for the biotech's Duchenne gene therapy are anticipated within weeks — an event investors are watching closely as it could be used in a wider range of patients than Sarepta's other three drugs. 

Regeneron's Libtayo for lung cancer

Regeneron is a latecomer to immunotherapy, having won the first approval for its drug Libtayo years after multiple rival medicines were already well established.

Sales to date have been modest, totaling roughly $251 million for the first nine months of 2020. But they could ramp up considerably with two new approval decisions expected this quarter — the most notable being in frontline lung cancer, one of the most competitive segments of oncology. 

Immunotherapies have changed the way many lung cancer patients are treated. A combination of Merck & Co.'s Keytruda and chemotherapy, for instance, is now standard treatment for a majority of people newly diagnosed with advanced non-small cell lung cancer, the most common form of the disease. 

Regeneron hopes to play a role too, and an approval for Libtayo monotherapy by the FDA's Feb. 28 decision date would put the biotech company in the mix with Merck, Roche, Bristol Myers Squibb and several others. Importantly for Regeneron, an approval would also help its plans to study different drug combinations. 

Regeneron has presented Libtayo results which Wall Street analysts found comparable to Keytruda monotherapy. The company also has an ongoing Phase 3 trial testing combinations of its drug with either chemotherapy or Bristol Myers' Yervoy against Keytruda head-to-head.

Results from that study are expected this year. Other tests combining Libtayo with cell therapies and oncolytic viruses are underway as well. 

Biogen's aducanumab for Alzheimer's 

The FDA is facing a no-win decision on Biogen's Alzheimer's treatment aducanumab. After collaborating with the company on review of its approval application in spite of mixed and controversial data, a panel of outside advisers voted decisively against the drug's benefit-risk profile. 

Now, if FDA follows the advisory committee's advice, it risks disappointing the patients, families and advocates who have pushed for new Alzheimer's therapies. If regulators ignore the committee, they risk damaging their reputation as independent arbiters of safety and effectiveness.

How the agency chooses will have enormous consequences, not least of which will be the ripple effects on Alzheimer's research. Many drugs that work similarly to aducanumab, which blocks the accumulation of a protein called amyloid beta in the brains of Alzheimer's patients, have failed previously. 

While most Wall Street analysts doubt the FDA will approve the drug, some are holding out the possibility of a surprise by the decision deadline of March 7. 

"There are two reasons that FDA could go against the recommendation," Stifel analyst Paul Matteis wrote in a Dec. 17 note to clients. "[First], FDA briefing documents were overwhelmingly positive, and [second] one thing that's clear is FDA believes aducanumab is safe, even in the community setting."

Bristol Myers Squibb and Bluebird bio's ide-cel for multiple myeloma

Rights to ide-cel, a cancer cell therapy, were acquired by Bristol Myers in its $74 billion takeover of Celgene two years ago. In their deal negotiations, the companies agreed to link U.S. approval of ide-cel and two other experimental drugs to a type of tradable security that promised Celgene shareholders an additional $6 billion. 

The much-scrutinized security is now void, after the FDA did not reach a decision on one of the other medicines by a Dec. 31, 2020, deadline set by Bristol Myers and Celgene. 

But ide-cel remains a critically important product for Bristol Myers and Bluebid bio and, if approved, would be the first cancer cell therapy cleared for use in multiple myeloma. Clinical trial results showed ide-cel to be a strongly potent treatment, eliminating or reducing patients' cancers in more than three quarters of study participants. While ide-cel causes significant side effects — severe in a small percentage of people — the treatment is expected to be approved by the FDA's target decision date of March 27, 2021.

Getting to this point, however, has taken longer than the companies originally expected. Last May, the FDA unexpectedly refused to accept the company's approval application, requesting more information on manufacturing. The notice, and the resulting time Bristol Myers and Bluebird needed to gather the additional information and resubmit its application, cost them several months.

From a business perspective, the delay could lessen the time Bristol Myers and Bluebird have without other cell therapy competition in multiple myeloma. A rival therapy being developed by Johnson & Johnson has looked similarly effective in clinical testing and should soon be under FDA review as well.

Other types of multiple myeloma treatments, including a kind of dual-targeting antibody drug, are quickly emerging, too. 

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