US Capitol Capsule: Cancer Therapies, Orphan Drugs Dominated 2015 Approvals; PCSK9s Arrived
This article was originally published in Scrip
Cancer therapies dominated US drug approvals in 2015, with the FDA's Center for Drug Evaluation and Research (CDER) also giving its nod to a record number of medicines that had gained orphan drug designation.
Indeed, of the 45 new molecular entities (NMEs) and novel biologics CDER approved in 2015 – which was four more than in 2014 and the most since 1996 when there were 53 – 21 had orphan status.
The year also was a game changer for patients with extremely high cholesterol – with the arrival of the proprotein convertase subtilisin/kexin 9 inhibitors onto the US market.
Sanofi SA's and Regeneron Pharmaceuticals Inc.'s Praluent (alirocumab) was first to clear the FDA's bar, gaining approval in July 2015, while Amgen Inc.'s Repatha (evolocumab) followed close behind about a month later.
The two PCSK9s have been in a fierce competition to be placed on payers' formularies, although Express Scripts Holding Co., the largest pharmacy benefit management company in the US, decided to put both Praluent and Repatha on its "national preferred formulary."
CDER also gave its blessing to two new heart failure drugs: Amgen's Corlanor (ivabradine) and Novartis AG's Entresto (sacubitril/valsartan).
Schizophrenia patients also have new options, with three first-of-their-kind medicines given the FDA's OK to enter the US market: Otsuka Pharmaceutical Co. Ltd.'s and H Lundbeck AS' Rexulti (brexpiprazole), Allergan PLC's Vraylar (cariprazine) and Alkermes PLC's Aristada (aripiprazole lauroxil).
By far, the most controversial approval by the FDA in 2015 was for Sprout Pharmaceuticals Inc.'s female libido pill Addyi (flibanserin), which was acquired, along with the company, just days later by Valeant Pharmaceuticals International Inc. for $1bn – a decision the latter firm may be regretting, given the drug's slow sales.
Over this past year, the FDA's Office of Hematology and Oncology Products (OHOP) approved 14 NMEs or new biologics for various forms of cancer – lung, breast, thyroid, colorectal and skin cancers; multiple myeloma; neuroblastoma; and liposarcoma and leiomyosarcoma – with the agency acting on many of those applications well-ahead of their user fee goal dates.
Of the six drugs OHOP approved in 2015 to treat non-small-cell lung cancer, three were NMEs or novel biologics: AstraZeneca PLC'sTagrisso (osimertinib), Eli Lilly & Co.'sPortrazza (necitumumab) and Genentech Inc.'s Alecensa (alectinib).
Patients with multiple myeloma also were big winners in 2015, with the FDA's OHOP granting NME or novel biologic approvals for Novartis' Farydak (panobinostat), Janssen Biotech Inc.'s and Genmab AS' Darzalex (daratumumab), Takeda Pharmaceutical Co.'s Ninlaro (ixazomib) and Bristol-Myers Squibb Co.'s and AbbVie Inc.'s Empliciti (elotuzumab).
Two new skin cancer drugs also secured approvals from OHOP in 2015: Genentech's and Exelixis Inc.'s Cotellic (cobimetinib), a MEK inhibitor, which was cleared as a therapy in combination with Zelboraf (vemurafenib), a kinase inhibitor marketed in the US by Genentech and Daiichi Sankyo Co. Ltd., to treat patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation; and Novartis' Odomzo (sonidegib), an oral selective smoothened inhibitor, which was approved as a treatment for adults with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.
On Feb. 3, 2015, the OHOP approved Pfizer Inc.'s Ibrance (palbociclib) in combination with letrozole as a first-line treatment for postmenopausal women with estrogen receptor positive, human epidermal growth factor receptor 2 negative advanced breast cancer who have not received previous systemic treatment for their advanced disease.
Ten days later, Eisai Co. Ltd. nabbed a US approval for its receptor tyrosine kinase inhibitor Lenvima (lenvatinib) as a treatment for locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer.
United Therapeutics Corp. had an important approval in March 2015 with the FDA's nod for Unituxin (dinutuximab), a GD2-binding monoclonal antibody indicated in combination with granulocyte-macrophage colony-stimulating factor, interleukin-2 and 13-cis-retinoic acid as a treatment for pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent multimodality therapy.
With that approval, United Therapeutics also won a rare pediatric disease priority review voucher – making history by garnering the highest amount ever paid for a voucher when it sold it to AbbVie in August for $350m.
The vouchers, however, have been a particularly sore issue for the FDA's John Jenkins, director of the Office of New Drugs, who has called the program flawed because it places the agency's "limited resources" in a situation where they are "for sale to the highest bidder."
Other new therapies cleared by the FDA's OHOP in 2015 included Taiho Pharmaceutical Co. Ltd.'s Lonsurf (trifluridine/tipiracil), which is indicated as a treatment for patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy and if RAS wild-type, an anti-EGFR therapy; and Janssen's Yondelis (trabectedin) as a treatment for metastatic or unresectable liposarcoma and leiomyosarcoma.
OHOP also approved Boehringer Ingelheim GmbH's Praxbind (idarucizumab) this part October under an accelerated approval as the first agent available to reverse the blood-thinning effects of the company's highly popular anticoagulant Pradaxa (dabigatran) in emergency surgery or urgent procedures or in situations when there's life-threatening or uncontrolled bleeding.
Tesaro Inc. was another firm given the FDA's go-ahead in 2015 to market a new drug: Varubi (rolapitant), which is indicated in combination with other antiemetic agents for use in adults to prevent delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.
Other NMEs or novel biologics approved in 2015 by CDER included Daiichi Sankyo's Savaysa (edoxaban), Novartis' Cosentyx (secukinumab), NPS Pharmaceutical Inc.'s Natpara (parathyroid horomone), Astellas Pharma Inc.'s Cresemba (isavuconazonium sulfate), Retrophin Inc.'s Cholbam (cholic acid), The Medicine Co.'s Kengreal (canegrelor), Vertex Pharmaceuticals Inc.'s Orkambi (lumacaftor 200mg/ivacaftor 125mg) and BMS' Daklinza (daclatasvir).
The agency also cleared Novo Nordisk AS' Tresiba (insulin degludec injection), Relypsa Inc.'s Veltassa (patiromer for oral suspension), GlaxoSmithKline PLC's Nucala (mepolizumab), Gilead Sciences Inc.'s Genvoya (elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide), Merck & Co.'s Bridion (sugammadex), Actelion Pharmaceuticals Ltd.'s Uptravi (selexipag), AstraZeneca's Zurampic (lesinurad), Alexion Pharmaceutical Inc.'s Strensiq (asfotase alfa) and Kanuma (sebelipase alfa) and Allergan's Avycaz (ceftazidime-avibactam), Kybella (deoxycholic acid) and Viberzi (eluxadoline).
The FDA's Center for Biologic Research and Development, whose director, Karen Midthun, announced her retirement this past October, also approved several new biologics in 2015, like Amgen's Imlygic, which was the first US-approved oncolytic virus therapy, and vaccines, including Bexsero, a meningitis B vaccine, which at the time belonged to Novartis but is now owned by GSK.
In other Washington news:
Whatever Happened To Industry's Interest In Ebola?
The story of the year for the biopharmaceutical industry in 2015 was most certainly the rumpus over drug prices. But a year earlier, it was Ebola, which was driven mostly by public fear and the fact the World Health Organization had almost nothing good to say about drug and vaccine makers, putting manufacturers under the microscope to prove their worth in a crisis.
Court Speeds Up Apotex Appeal In Amgen Biosimilar Suit
The US Court of Appeals for the Federal Circuit granted Apotex Inc.'s motion – or at least, in part – for an expedited appeal of a Florida court's decision to impose a preliminary injunction that prevents the firm from marketing its yet-to-be approved pegfilgrastim biosimilar until 180 days after FDA licenses the product.
Supreme Court Review Of Biosimilars Law Closer?
Novartis unit Sandoz submitted a request to the US Supreme Court on Dec. 23, 2015 seeking an extension of the deadline from Jan. 14 to Feb. 16 to file a writ for certiorari in a lawsuit brought by Amgen Inc. involving the Biologics Price Competition and Innovations Act. On Dec. 29, 2015, Chief Justice John Roberts granted that request, although Sandoz is under no obligation to actually file the cert petition.
AbbVie: Hearing Needed On Biosimilars Interchangeability
In a new citizen petition, AbbVie Inc. argued that a public hearing is needed before the FDA issues its biosimilars interchangeability guidance.
Shkreli's Empire Collapses: KaloBios Seeks Bankruptcy Protection
KaloBios Pharmaceuticals Inc., which fired Martin Shkreli from his CEO job after he was arrested for fraud, filed for chapter 11 bankruptcy protection on Dec. 30, 2015.
KaloBios Seeks Appeal Of Nasdaq Delisting
KaloBios Pharmaceuticals Inc. on Dec. 29, 2015 said it is appealing the Nasdaq's decision to delist the company's securities from the stock market. A hearing has been set for Feb. 25.
Anavex Thumped On SEC Subpoena, Probe
Shares of Anavex Life Sciences Corp. were smacked on Dec. 29, 2015 – tumbling as low as 21.2% in morning trading – after the company revealed it had been hit with a subpoena from the Securities and Exchange Commission declaring it was conducting a formal investigation of the firm.
Valeant CEO Hospitalization, Medical Leave Vexes Investors
Shares of Valeant Pharmaceuticals International Inc. sank about 11% on Dec. 28, 2015 over concerns about the hospitalization due to a "severe case of pneumonia" and subsequent medical leave of the company's CEO Michael Pearson, whose firm is under congressional investigation for price gouging.
This and past US Capitol Capsule columns are available at http://www.scripintelligence.com/capitolcapsule/