Keeping Track: A Week Of Calm As Shutdown Drags On

The latest drug development news and highlights from our US FDA Performance Tracker.

Although the US FDA has been largely able keep up its review functions throughout the government shutdown so far, it remained a quiet week of drug development announcements. Here's your news in brief:

FDA delayed the user fee goal date of AMAG Pharmaceuticals Inc.’s hypoactive sexual desire disorder (HSDD) drug Vyleesi (bremelanotide) with a request for data from a frequent-dosing study.

The first announced breakthrough therapy status of the year went to Novartis AG, which earned the designation for its anti-P-selectin monoclonal antibody crizanlizumab (SEG101).

Clinuvel Pharmaceuticals Ltd. earned a curiously-timed priority review goal date for its erythropoietic protoporphyria (EPP) treatment Scenesse (afamelanotide), as the company first submitted the new drug application (NDA) in June 2018.

Additionally, Agios Pharmaceuticals Inc. is seeking to expand Tibsovo's (ivosidenib) reach in acute myeloid leukemia (AML) by filing a supplemental new drug application (sNDA) for newly diagnosed patients.

Now, here's your news in less brief:

Frequent-Dosing Study Request Pushes Back Bremelanotide Goal Date

An FDA-requested frequent-dosing study has pushed back the user fee goal date of AMAG’s sexual dysfunction drug Vyleesi (bremelanotide) by three months to June 23.

The agency has specifically asked for such a study with premenopausal volunteers to assess short-term daily use, Palatin Technologies Inc., which is licensing Vyleesi to AMAG in North America, said in an 8-K dated Jan. 7. Palatin noted the study has been initiated and that study results are expected to be submitted prior to the new goal date.

The two companies said last year that FDA is planning hold to an advisory committee to discuss Vyleesi when the agency accepted the new drug application (NDA) for a standard review. (Also see "Keeping Track: Mylan Wins First US FDA Approval For Neulasta Biosimilar, But Lands A CRL For Insulin Glargine; Genentech Nabs Broad Full Approval For Venclexta, PV Indication For Rituxan" - Pink Sheet, 8 Jun, 2018.) FDA, however, has not yet announced a date for a meeting.

If approved, Vyleesi, a first-in-class melanocortin 4 receptor agonist, would be the second drug indicated for treatment of HSDD in premenopausal women. (Also see "Keeping Track: Submissions Galore, Blincyto Supplemental Approval, And Priority Review For Opdivo/Yervoy Combo" - Pink Sheet, 30 Mar, 2018.) The drug has a novel mechanism of action that works by activating endogenous melanocortin pathways in the brain. (Also see "Keeping Track: Submissions Galore, Blincyto Supplemental Approval, And Priority Review For Opdivo/Yervoy Combo" - Pink Sheet, 30 Mar, 2018.)

In two Phase III trials, Vyleesi met two co-primary endpoints related to self-reported improvements in desire and reduction in distress in two Phase III trials.
(Also see "Will Palatin's Phase III Female Sex Endpoint Swap Pass With FDA?" - Pink Sheet, 2 Nov, 2016.) and (Also see "FDA Adds New Co-Primary Endpoint For Female Sexual Desire Drugs" - Pink Sheet, 26 Oct, 2016.) 

Sprout Pharmaceuticals Inc.'s Addyi (flibanserin) is the only drug approved in the HSDD setting. But the approval of Addyi came following an extensive public relations campaign, which AMAG CEO William Heiden believes backfired. Heiden said the discussion about Vyleesi will remain scientifically-based. (Also see "BIO Notebook Day 4: Gottlieb Seeks Early Engagement On Gene Therapy; Ireland’s Brexit Opportunities; AMAG’s Bremelanotide Strategy; Alzheimer’s ‘Learnings’ " - Pink Sheet, 7 Jun, 2018.)

BTD In Hand, Novartis Eyes H1 2019 BLA For Sickle Cell Pain

Novartis hopes its newly awarded breakthrough therapy designation (BTD) for crizanlizumab will help the anti-P-selectin monoclonal antibody to a biologics license application (BLA) filing in the first half of 2019.

The BTD covers use of crizanlizumab for prevention of vaso-occlusive crises (VOCs) in patients of all genotypes with sickle cell disease (SCD). Novartis acquired the humanized antibody, which reduces multicellular adhesion, with its 2016 acquisition of Selexys Pharmaceuticals Corp. (Also see "Novartis Buys Selexys As Competitors Stumble In Sickle Cell" - Scrip, 21 Nov, 2016.)

The breakthrough designation is based on data from the 52-week Phase II SUSTAIN trial of crizanlizumab, which compared the once-monthly infusion with placebo. The median annual rate of VOCs leading to health care visits was 1.63 in rizanlizumab patients and 2.98 for placebo, for a 45.3% reduction in the median annual rate. More patients receiving the antibody experienced no VOCs: 35.8% versus 16.9%. (Also see "Sickle Cell Data Show Value Of Novartis’s Recently Acquired SEG101" - Scrip, 5 Dec, 2016.)

At the recent American Society of Hematology meeting, Novartis presented a post hoc analysis of SUSTAIN showing greater reductions in VOCs in patients who were adherent to the treatment protocol.

SUSTAIN is part of the SENTRY clinical trial program for crizanlizumab in SCD. Active trials in the program include the Phase III stand study in patients 12 years and older, the Phase II SOLACE-adults and SOLACE-kids trials, and SUCCESSOR, a retrospective cohort study following adult SCD patients in the US.

Chugai's Satralizumab Nabs BTD In Race For Neuromyelitis Optica Therapy

Chugai Pharmaceutical Co. Ltd. ’s Phase III SAkuraSky trial earned a breakthrough designation for its anti-interleukin-6 recycling antibody satralizumab for treatment of neuromyelitis optica and neuromyelitis optica spectrum disorders (NMO/NMOSD), a rare autoimmune disorder of the central nervous system.

While no therapies are approved for NMO/NMOSD, three compounds are in pivotal development: satralizumab; the CD19-binding antibody inebilizumab from MedImmune LLC spin-off Viela Bio; and Alexion Pharmaceuticals Inc.'s complement inhibitor Soliris (eculizumab). Viela has said it is preparing to submit a BLA in the first half of 2019; Alexion is also expected to submit for a new indication for Soliris in 2019. (Also see "Viela Adds Momentum To Burgeoning NMOSD Market With Pivotal Inebilizumab Results" - Scrip, 3 Jan, 2019.)

Chugai’s 83-patient Phase III SAkuraSky trial tested satralizumab added to baseline therapy with immunosuppressants or steroids. The trial randomized patients to subcutaneous injection of the antibody or placebo every month, after more frequent dosing for the first month of administration. The double-blind portion of the study continued until the total number of protocol-defined relapses reached 26, Chugai said; all patients could then receive satralizumab in an open-label extension.

On the trial’s primary endpoint, based on time to first relapse during the double-blind period, satralizumab significantly reduced risk of relapse by 62%, Chugai reported at the ECTRIMS conference in Germany in October.

A subgroup analysis of the trial looked at NMOSD patients by antibody status. The disorder is believed to involve entry of an autoantibody known as anti-aquaporin-4 (AQP4) into the CNS, Chugai said, but about one-third of NMOSD patients are AQP4-IgG seronegative. In SAkuraSky, satralizumab showed a 79% reduction in risk of relapse compared with placebo in the AQP4 Ab-positive subgroup, while the AQP4 Ab-negative group showed a 24% reduction.

Clinuvel Announces Oddly-Timed Priority Review For Scenesse

Clinuvel's Scenesse has landed a priority review user fee goal date of July 8, as the company is seeking an approval for the prevention of phototoxicity and anaphylactoid reactions in adults with erythropoietic protoporphyria (EPP).

But the timing of the goal date appears strange in light of Clinuvel's previous submission announcements.

The drugmaker announced that it completed the rolling submission of the NDA in June 2018. (Also see "Keeping Track: Pre-Independence Day Fireworks Crackle At US FDA With Burst Of Approvals And Filings" - Pink Sheet, 30 Jun, 2018.) A priority review for a novel product sets the user fee date eight months from the date of the completed submission, which means the goal date would have been pegged for February 2019 or earlier.

A company spokesperson told the Pink Sheet that, "The FDA has never issued a negative opinion or asked Clinuvel to withdraw, nor did it issue a [refuse-to-file]. Rather, the agency needed more time in a complex disorder and a novel formulation, and extended the validation period, focused on quality, manufacturing and the product."

The European Medicines Agency first approved Scenesse in 2014, and Clinuvel's US NDA contains real-world data from the European post-marketing experience in addition to data from two Phase III trials. (Also see "Clinuvel’s US Filing For EPP Drug Scenesse Includes Real World Evidence From Europe" - Pink Sheet, 27 Jun, 2018.) But the drug has faced barriers in the UK, as the National Institute for Health and Care Excellence (NICE) previously recommended that the drug should not be made available through the National Health Service. (Also see "Not Out Of The Dark Yet: UK’s NICE Turns Down Clinuvel’s Phototoxicity Drug Scenesse" - Pink Sheet, 22 Dec, 2017.)

The NICE appeals panel, however, threw Clinuvel a lifeline, as it instructed the health technology assessment body to re-examine its decision. (Also see "UK Appeal Panel Tells NICE To Revisit Scenesse Rejection" - Pink Sheet, 12 Oct, 2018.)

Agios Files Tibsovo sNDA For Expanded AML Label

Agios didn't waste much time pursuing a broader reach for its isocitrate dehydrogenase-1 (IDH1) inhibitor Tibsovo in the acute myeloid leukemia (AML) space.

The company announced in a Jan. 7 release that it filed an sNDA in December for Tibsovo as a monotherapy for the first-line treatment of patients with newly diagnosed AML with an IDH1 mutation who are not eligible for standard therapy. A priority review would slate the user fee goal date for June 2019 or earlier.

It was only around five months earlier that Agios scored its initial approval for the treatment of adults with relapsed or refractory AML with a susceptible IDH1 mutation. (Also see "Keeping Track: US FDA Approvals For Tibsovo, Kisqali And Second Neupogen Biosimilar" - Pink Sheet, 22 Jul, 2018.) and (Also see "Tibsovo Approval Makes Agios’ Second AML Approval In A Year; Priced At $26k For 30 Days" - Scrip, 20 Jul, 2018.)

In the same Jan. 7 announcement, Agios noted it plans to submit another sNDA for Tibsovo by year-end for the second-line or greater treatment of IDH1m cholangiocarcinoma.

[Editor's note: This story has been updated with Clinuvel's explanation of the Scenesse submission timeline.]