Keeping Track: Oncology Announcements, Priority Review Vouchers Continue To Pile Up

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

Oncology application announcements have continued to mount in the run up to the American Society for Clinical Oncology (ASCO) annual meeting in Chicago.

Priority review vouchers also earned the spotlight, as two companies – Amicus Therapeutics Inc.and Abeona Therapeutics Inc.– each received a rare pediatric disease designation for their respective epidermolysis bullosa (EB) candidates, while KaloBios Pharmaceuticals Inc. is anticipating a tropical disease review voucher for its recently submitted Chagas disease candidate.

Breakthrough therapy announcements have set a new monthly high, with Alnylam Pharmaceuticals bmost recently receiving the designation for its ALN-AS1 (givosiran). (See sidebar for related story.)

And Novo Nordisk AS somehow managed to avoid being hit with any postmarketing study requirements for its newly approved hemophelia B biologic Rebinyn (nonacog beta pegol), despite an advisory committee and FDA itself expressing concerns about monitoring saety of the treatment. (See sidebar for related story.)

Churchill Submits NDA For Slightly Reformulated Abiraterone Acetate

The recent pileup of oncology applications is continuing, with Churchill Pharmaceuticals LLC announcing May 23 the submission of an NDA to FDA for its for its CYP17 inhibitor Yonsa (abiraterone acetate) designed for the treatment of metastatic castration-resistant prostate cancer in combination with methylprednisolone.

Submission is based on the results of Churchill's STAAR Study, which compares YONSA and methylprednisolone against Janssen Inc.'s Zytiga (abiraterone acetate) in combination with prednisone.

Yonsa appears to only be a slight reformulation on Zytiga. A 500 mg dose of Yonsa was found to be bioequivalent with a 1000 mg a dose of Zytiga, as measured by a primary endpoint of comparative lowering of total testosterone at pharmacokinetic steady-state. If approved, it would likely be seen by payors as a "me too" drug.

Churchill President Scott Megaffin described the drug in a statement as "a potential future option for men" with metastatic castration-resistant prostate cancer. Yonsa has a user fee date of March 23, 2018.

The submission is just one of the most recent oncology announcements as the ASCO annual meeting began June 2. The meeting regularly causes a spike in announcements about regulatory progress of oncology candidates. Bristol-Myers Squibb Co., Novartis AG and Merck & Co. Inc. have also made oncology-related announcements about products in recent weeks. (Also see "Keeping Track: Oncology Filings Galore In Run-Up To ASCO Meeting" - Pink Sheet, 28 May, 2017.)

Jazz Gets Priority Review For Leukemia Candidate

Adding to the oncology updates, Jazz Pharmaceuticals PLC is positioned for an autumn approval from FDA for its acute myeloid leukemia (AML) candidate Vyxeos (cytarabine and daunorubicin), announcing the receipt of priority review from the agency May 31.

Vyxeos has shown a benefit in in older, high-risk AML patients, who often cannot tolerate the standard "7+3" induction regimen of cytarabine and an anthracycline like daunorubicin. It previously received a breakthrough therapy designation for adults with therapy-related AML or AML with myelodysplasia-related changes. (Also see "Keeping Track: Teva's Austedo Clears US FDA, Merck Sitagliptin CV Outcomes Labeling Draws Complete Response" - Pink Sheet, 7 Apr, 2017.)

The candidate – which has a user fee date of Sept. 30 – had also received a fast track designation for treatment of older patients with secondary AML. (Also see "Keeping Track: Chugai Delivers Two Breakthroughs For Roche; FDA Continues To Wrestle With Opioid Regulation" - Pink Sheet, 7 Oct, 2016.)

In a Phase III trial, Vyxeos demonstrated a median overall survival of 9.6 months compared with 6 months for the 7+3 arm, as well as a modest improvement in event-free survival. (Also see "Keeping Track: Teva's Austedo Clears US FDA, Merck Sitagliptin CV Outcomes Labeling Draws Complete Response" - Pink Sheet, 7 Apr, 2017.) A more recent subgroup analysis a subgroup analysis from the Phase III study of survival after hematopoietic stem cell transplant in older, high-risk patients found a 10.25-month median overall survival for the standard regimen. while the Vyxeos arm did not reach median overall survival. (Also see "Keeping Track: Teva's Austedo Clears US FDA, Merck Sitagliptin CV Outcomes Labeling Draws Complete Response" - Pink Sheet, 7 Apr, 2017.)

KaloBios Submits IND For Chagas Disease Candidate, Hopes To Sell Eventual PRV

KaloBios, a company perhaps most famous for being briefly led by Martin Shkreli, announced May 30 that it has submitted an investigational new drug (IND) application to FDA for its Chagas disease treatment benznidazole.

Chagas disease was added to FDA's list of neglected tropical diseases in 2015. Current KaloBios CEO Cameron Durrant tells the Pink Sheet in a statement that he expects benzindazole to be eligible for a neglected tropical disease priority review voucher, and that the company will look to sell the voucher if receives one.

Durrant says selling the voucher would be "a way of infusing non-dilutive capital into the company to develop our promising pipeline ahead," including lenzilumab, which is being developed for the treatment of chronic myelomonocytic leukemia and juvenile myelomonocytic leukemia.

Selling a voucher may not be the same cash influsion that it once was. The most recent voucher transaction announced was Sarepta Therapeutics Inc.'s sale (of the one it received for its Duchenne muscular dystrophy treatment Exondys 51, eteplirsen). to Gilead Sciences Inc. for $125 million. There have been at least six other sales of priority review vouchers, ranging from $67.5 million to $350 million. (Also see "Gilead Buys Its Third Priority Review Voucher, But Is The Mania Over?" - Pink Sheet, 21 Feb, 2017.)

Benznidazole will be reviewed through the 505(b)(2) pathway, which FDA said in an October 2016 guidance would be eligible for a priority review voucher. (Also see "KaloBios Can Get Priority Review Voucher With 505(b)(2) Chagas Application" - Pink Sheet, 5 Jan, 2017.)

KaloBios is expected to file a new drug application (NDA) for the compound in the first quarter of 2018.

Amicus, Abeona Nab Rare Pediatric Disease Designation For EB Candidates

As Amicus gears up to become the first drugmaker to tap into the epidermolysis bullosa market, FDA has awarded the company rare pediatric disease designation for its EB candidate SB-101.

Amicus said May 31 it plans to report top-line data from the drug's 160-patient, placebo-controlled Phase III ESSENCE study during the third quarter of 2017. Primary endpoints include time to complete target wound closure and the proportion of patients experiencing complete closure of their target wound.

According to the company, SB-101 is the first EB candidate to enter Phase III development.

A company spokeswoman tells the Pink Sheet that Amicus – a clinical-stage company like KaloBios – would sell the priority review voucher if the product is approved. Amicus' entre pipeline consists of rare disease candidates, the spokesperson says, which are already typically eligible for priority review. The company has not yet discussed an NDA submission time frame, and is expected to provide more information on the timelines after the final data are available.

SD-101 previously received a breakthrough therapy designation in 2013, when it became one of the first companies to get the designation.

Abeona also announced May 30 that it scored a rare pediatric disease designation for its EB candidate EB-101, which is currently Phase I/II development.

The company did not return a request for comment regarding whether it would keep or sell the priority review voucher it receives if the drug is approved. Being a clinical-stage company, however, it is possible Abeona will sell the voucher to have extra cash on hand. According to the company's May 15 10-Q filing, Abeona had $63,212,000 worth of cash and cash equivalents.

Sunovion COPD Combination Product Lands CRL

Sunovion Pharmaceuticals Inc.'s plans for a summer approval of its chronic obstructive pulmonary disease (COPD) combination product SUN-101/eFlow (aclidinium) could be on hold, as the company announced May 26 the receipt of a CRL from FDA.

The magnitude of the CRL is unclear, although Sunovion notes that the company is not required to conduct any additional clinical studies of the product. The company is "confident in SUN-101/eFlow and committed to bringing this innovation therapy to COPD patients in the U.S. as quickly as possible," but declined to provide more information about the letter.

Sunovion was previously hoping to gain approval for the product in the summer of 2017. (Also see "Keeping Track: Novartis, Calardius Pick Up Speed; ADMA Stumbles" - Pink Sheet, 5 Aug, 2016.)

If approved, the product would enter an already crowded field of bronchodilator therapies for COPD, including Boehringer Ingelheim Pharmaceuticals Inc.Spiriva (tiotropium) and AstraZeneca PLC's Bevespi Aerosphere (glycopyrrolate and formoterol fumarate).

(For more information on agency action letters, see the Complete Response Letters chart on the FDA Performance Tracker.)

FDA Approves First Generics Of Strattera Without Delays

FDA has approved the first generic versions of Eli Lilly & Co.'s attention-deficit/hyperactivity disorder (ADHD) drug Strattera (atomoxetine), seemingly without the sponsors running into any delay tactics along the way.

Apotex Inc., Teva Pharmaceuticals USA Inc., Aurobindo Pharma Ltd. and Glenmark Pharmaceuticals Ltd. all gained approval May 30 to market a copycat of Strattera.

A Teva spokesperson tells the Pink Sheet that the approval came "according to plan."

Lilly's patents – which essentially ran for an extra six months with pediatric exclusivity – expired May 26, 2017, four days before the approval of the generics.

Nicox Bounces Back From CRL, Gets Approval For Zerviate

Nicox Inc. announced May 31 that the FDA has approved Zerviate (cetirizine ophthalmic solution 0.24%) indicated for ocular itching associated with allergic conjunctivitis, after initially suffering a setback stemming from manufacturing issues.

The company initially received a CRL for Zerviate – which was initially developed by Aciex Therapeutics, which was acquired by NicOx in 2014 – citing a Good Manufacturing Practice (GMP) inspection at a third party facility producing the active pharmaceutical ingredient (API). (Also see "Keeping Track: FDA Rejects Mealtime Insulin, Antihistamine; Misses Goal For Another Opioid" - Pink Sheet, 14 Oct, 2016.)

According to Nicox, Zerviate is the first topical ocular formulation of the antihistamine cetirizine, which is available over-the-counter (OTC) in several oral formulations, including as Johnson & Johnson’s Zyrtec.

Nicox CEO Michele Garufi said in a statement that partnering discussions are "underway" for US commercialization rights.

Indivior Hopes For Fourth Quarter Approval For OUD Treatment

Indivior PLC announced May 30 that it submitted an NDA for its moderate-to-severe opioid use disorder (OUD) treatment RBP-6000, as it hopes to gain approval before the end of 2017.

A once-monthly injectable buprenorphine treatment, RBP-6000 is part of a broader treatment plan for OUD that also includes counseling and psychosocial support.

A company spokesperson tells the Pink Sheet that Indivior believes it could obtain marketing authorization in the fourth quarter of 2017 if FDA awards priority review status. Indivior is hoping to separate itself from other OUD treatments by using long-acting formulations of buprenorphine to improve treatment compliance. (Also see "Indivior Leaps On Phase III Data For Depot Opioid Addiction Treatment" - Scrip, 18 Aug, 2016.)

The submission followed the completion of a placebo-controlled Phase III study, where RBP-6000 showed a statistically significant higher percentage of negative urine samples, as well as self-reports negative for illicit opioid use, compared with placebo.

Indivior will present the results of the trial June 21 at the 79th Annual Scientific Meeting of the College on Problems of Drug Dependence (CPDD) meeting.

Priority Review Puts Ultragenyx's Sly Syndrome Candidate On Track For Fall Approval

FDA has awarded Ultragenyx Pharmaceutical Inc.'s recombinant human beta-glucuronidase (rhGUS or UX003) priority review, slating an approval decision for the ultra-rare Mucopolysaccharidosis VII (MPS VII or Sly syndrome) candidate of Nov. 17.

A 12-patient Phase III trial of subjects between ages 5 and 35 examined percent reduction in urinary glycosaminoglycans excretion after 24 weeks of treatment.

Ultragenyx has also filed for marketing authorization with the European Medicines Agency (EMA), with an opinion from the Committee for Medicinal Products for Human Use (CHMP) expected in the first half of 2018.