Migraine, cholesterol upstarts top the list of FDA decisions to watch this quarter

FDA Building 2
Drugs like Bristol-Myers Squibb's ozanimod come with blockbuster expectations if approved. (FDA)

It's a new year, which means it's a new opportunity for drugmakers hoping to pass FDA muster for new therapies––some of which could be sniffing after blockbuster sales. 

In the first quarter, the FDA is set to decide on a group of new drugs that come with high hopes, high scrutiny and, in some cases, raised eyebrows from the agency staff who have reviewed them.

Here are the FDA finish lines we'll be watching most closely over the next three months. 

Drug: Tazemetostat
Indication: Advanced epithelioid sarcoma
Company: Epizyme
PDUFA date: Jan. 23

Despite facing some scathing criticism from FDA staff, Epizyme's sarcoma fighter tazemetostat sailed through an advisory committee session with a unanimous vote in December on its way to an approval decision date Jan. 23.

Epizyme is seeking approval for tazemetostat in patients with advanced epithelioid sarcoma who can’t undergo surgery to remove their tumors. It's a rare cancer of the soft tissue that can spread to other areas. It's also difficult to diagnose, so it may not be discovered until its later stages. The drug’s application is based on data from about 100 patients who made up two groups—cohorts 5 and 6—in a larger study that tested tazemetostat in various tumor types.

In terms of peak sales, the indication is small––Jefferies analyst Michael Yee put the U.S. market at $50 million––but it would get Epizyme's foot in the door. The company's also seeking an approval for tazemetostat in follicular lyphoma, which has a market closer to $500 million.

RELATED: Epizyme's sarcoma drug sails through FDA panel with unanimous vote

There's a lot on the line for Esperion with its cholesterol-fighter bempedoic acid after the drugmaker has withstood a dwindling share price and faces a staggered loan tied to the med's approval decision Feb. 21. 

Esperion faces an FDA decision on bempedoic acid as a solo treatment for high cholesterol and as a combo treatment with ezetimibe, a Merck & Co. cholesterol-fighter marketed as Zetia.

In a yearlong phase 3 trial released in May 2018, bempedoic acid showed it can lower LDL cholesterol levels by an additional 20% over 12 weeks in high-risk patients taking statins. However, the study also reported 13 deaths in its treatment arm, a rate of 0.9%, about three times that seen with placebo.

On a later conference call with investors, Esperion’s senior vice president for clinical research, Bill Sasiela, said the deaths stemmed from an older, less-healthy study population, two-thirds of which were current or former smokers.

In June, Esperion struck a $200 million funding agreement for a staggered loan, which granted Esperion $125 million up front with up to $75 million to follow as bempedoic acid wins FDA approval and comes to market. Over the last six months, Esperion's shares have dropped around 2.45% to $59.84. 

RELATED: Esperion’s phase 3 LDL study raises flags with treatment-arm deaths

Drug: Teprotumumab
Indication: Thyroid eye disease
Company: Horizon Therapeutics
PDUFA date: March 8

Horizon Therapeutics is hoping to pivot away from its reputation of repurposing older meds at astronomical prices into rare diseases, and the approval of eye drug teprotumumab could help it get over the hump. 

The treatment for thyroid eye disease (TED) received an FDA advisory committee's unanimous backing in December ahead of its March 8 decision date. Teprotumumab inhibitors the insulin-like growth factor type 1 receptor for TED, a rare autoimmune disorder that can lead to blurred or double vision. Patients typically seek treatment when they notice their eyes bulging in photos or that their eyes and eyelids constantly seem to be red and swollen, Raymond Douglas, M.D., Ph.D., one of the leaders of teprotumumab’s phase 3 study, said in a previous interview. 

If approved, teprotumumab would be the first treatment for TED that changes the course of the disease rather than just addressing symptoms. Today, patients take steroids to keep swelling at bay or undergo bone-shaving surgery that returns the eyeball to a normal position in the eye 

RELATED: Horizon's eye drug teprotumumab wins FDA panel backing in unanimous vote

Drug: Ozanimod
Indication: Multiple sclerosis
Company: Bristol-Myers Squibb
PDUFA date: March 25

Touted as one of the "Big 5" late-stage candidates in Bristol-Myers Squibb's megamerger with Celgene, MS med ozanimod has walked a troubled path to its March 25 decision date. 

In June, U.S. and European regulators accepted Celgene’s ozanimod filings to treat patients with relapsing forms of multiple sclerosis. Analysts have blockbuster expectations for the drug, even after its embarrassing refuse-to-file response from the FDA last year.

It was the latest in a series of told-you-so moments for Bristol-Myers execs since they struck their Celgene buyout in early January 2019. They scored a key investor vote in support of the deal, despite activists agitating against it, for instance, and cleared an extended FTC review. The deal finally closed in late November.

If approved, ozanimod would follow in the steps of other "Big 5" candidates like Reblozyl (luspatercept), which grabbed a green light in November to treat anemia in patients with beta thalassemia, and JAK inhibitor Inrebic (fedratinib), which won an August nod for myelofibrosis.

RELATED: Hey, naysayers: Bristol-Myers' Celgene buy just chalked up another point in its favor

Drug: Rimegepant
Indication: Migraine treatment and prevention
Company: Biohaven Pharmaceuticals
PDUFA date: Q1 2020

It may have lost its battle to bring the first oral CGRP-class drug to market—that honor went to Allergan in late December—but Biohaven Pharma is still hoping its migraine fighter rimegepant will win an FDA nod despite some underwhelming data backing up its case. 

Data from two phase 3 studies released in March 2018 showed a single dose of rimegepant beat placebo at relieving pain—or another symptom  patients found most bothersome—at the two-hour mark after dosing. 

All told, a little over 19% of patients on rimegepant were pain-free at the two-hour time point, compared with 14% of the placebo group, with the difference between the two groups appearing to widen beyond two hours. Similarly, around 37% of patients were free of their most bothersome symptom (MBS) compared with around a fourth of subjects in the control arm.

Also, fewer patients on the active drug required rescue therapy with current drugs such as triptans.

Besides Allergan's uprogepant, approved under the brand name Ubrelvy, rimegepant would also face competition from the current class of injectable CGRPs, including Novartis and Amgen’s Aimovig as well as Teva’s Ajovy and Eli Lilly’s Emgality. All three of those drugs won approvals over the last year and a half. 

RELATED: Biohaven says oral migraine drug set for 2019 filing, but data disappoints

Other approvals of note

Aimmune's controversial peanut allergy med AR101, set to be branded as Palforzia, received a 7-2 recommendation from an FDA advisory committee ahead of its late January PDUFA date. Palforzia, which desensitizes patients by giving them gradually increasing doses of peanut protein, could be a game-changer in the food allergy field, where avoidance is the most common treatment. FierceBiotech