A Banner Year for NMEs in 2015; Will It Continue in 2016?By
In 2015, the US Food and Drug Administration’s Center for Drug Evaluation and Research approved 45 new molecular entities (NMEs), a recent high, surpassing 2014’s level of 41 NME approvals and 2012’s 39 NME approvals. .
So which companies fared the best in 2015 and which products are best poised for commercial success? DCAT Value Chain Insights (VCI) takes an inside look.. DCAT Value Chain Insights (VCI) takes an inside look.
NME approvals in 2015
Last year was a banner year for approval of NMEs with 45 new molecular entities (NMEs) approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research, a recent high. Table I outlines the 45 NMEs approvals in 2015. Of the 45 NMEs approved, 32 were small molecules (new drug applications (NDAs)), one is an insulin analogue approved as a NDA, and 12 are biologics (biologics license applications (BLAs) (see Table I).
The small-molecule approvals in 2015 were: Actelion Pharmaceuticals’ Uptravi (selexipag); Alkmeres’ Aristada (aripiprazole lauroxil); Allergan’s (formerly Actavis) Viberzi (eluxadoline), Avycaz (ceftazidime-avibactam), Kybella (deoxycholic acid), and Vraylar (cariprazine); Amgen’s Corlanor (ivabradine); Asklepion Pharmaceuticals/Retrophin’s Cholbam (cholic acid); Astellas Pharma’s Cresemba (isavuconazonium); AstraZeneca’s Tagrisso (osimertinib) and Zurampic (lesinurad); Bristol-Myers Squibb’s Daklinza (daclatasvir); Daiichi Sankyo’s Savaysa (edoxaban); Eisai’s Lenvima (lenvatinib); Gilead Sciences’ Genvoya (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide); Johnson & Johnson’s Yondelis (trabectedin); Merck & Co. ‘s Bridion (sugammadex); Novartis’ Farydak (panobinostat), Odomzo (sonidegib), and Entresto (sacubitril/valsartan); Otsuka Pharmaceutical’s Rexulti (brexpiprazole); Pfizer’s Ibrance (palbociclib); Roche’s Cotellic (cobimetinib) and Alecensa (alectinib); Sprout Pharmaceuticals’ Addyi (flibanserin) (Valeant Pharmaceuticals is acquiring Sprout Pharmaceuticals); Taiho Oncology’s Lonsurf (trifluridine and tipiracil); Tesaro’s Varubi (rolapitant); Takeda Pharmaceuticals’ Ninlaro (ixazomib); The Medicines Company’s Kengreal (cangrelor); Vertex Pharmaceuticals’ Orkambi (lumacaftor and ivacaftor); and Wellstat Therapeutics’ Xuriden (uridine triacetate).
Twelve biologics were approved in 2015: Alexion Pharmaceuticals’ Strensiq (asfotase alfa) and Kanuma (sebelipase alfa); Amgen’s Repatha (evolocumab); Boehringer Ingelheim’s Praxbind (idarucizumab); Bristol-Myers Squibb’s Empliciti (elotuzumab); Eli Lilly’s Portrazza (necitumumab); GlaxoSmithKline’s Nucala (mepolizumab); Johnson & Johnson’s Darzalex (daratumumab); Novartis’ Cosentyx (secukinumab); Sanofi/Regeneron Pharmaceuticals’ Praluent (alirocumab); Shire/NPS Pharmaceuticals’ Natpara (parathyroid hormone); and United Therapeutics’ Unituxin (dinutuximab). Novo Nordisk’s Tresiba (insulin degludec injection), a long-acting basal human insulin analog produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification (it was approved as a NDA and not as a BLA)
|Table I: 2015 New Molecular Entities (New Drug Applications (NDAs) and Original Biologics License Applications (BLAs) Approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research.|
|Company||Property name (active ingredient); application type;||Indication|
|Actelion Pharmaceuticals||Uptravi (selexipag); NDA||Pulmonary arterial hypertension|
|Alexion Pharmaceuticals||Strensiq (asfotase alfa); BLA||Perinatal, infantile, and juvenile-onset hypophosphatasia|
|Alexion Pharmaceuticals||Kanuma (sebelipase alfa); BLA||Lysosomal acid lipase deficiency|
|Alkermes||Aristada (aripiprazole lauroxil) extended-release injection; NDA||Schizophrenia|
|Allergan||Viberzi (eluxadoline); NDA||Irritable bowel syndrome with diarrhea|
|Allergan||Avycaz (ceftazidime-avibactam); NDA||Complicated intra-abdominal infections in combination with metronidazole, and complicated urinary tract infections, including kidney infections|
|Allergan/Forest Laboratories||Vraylar (cariprazine); NDA||Schizophrenia and bipolar disorder in adults.|
|Allergan/Kythera Biopharmaceuticals||Kybella (deoxycholic acid); NDA||Moderate-to-severe fat below the chin|
|Amgen||Corlanor (ivabradine): NDA||To reduce hospitalization from worsening heart failure|
|Amgen||Repatha (evolocumab); BLA||For some patients who are unable to get their low-density lipoprotein (LDL) cholesterol under control with current treatment options|
|Asklepion Pharmaceuticals/Retrophin||Cholbam (cholic acid); NDA||Pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects and for patients with peroxisomal disorders|
|Astellas Pharma||Cresemba (isavuconazonium; NDA||Invasive aspergillosis and invasive mucormycosis|
|AstraZeneca||Tagrisso (osimertinib); NDA||Advanced non-small cell lung cancer in patients whose tumors have a specific epidermal growth factor receptor (EGFR) mutation (T790M) and whose disease has gotten worse after treatment with other EGFR-blocking therapy|
|AstraZeneca||Zurampic (lesinurad); NDA||To treat high levels of uric acid in the blood (hyperuricemia) associated with gout|
|Boehringer Ingelheim||Praxbind (idarucizumab); BLA||In patients who are taking the anticoagulant Pradaxa (dabigatran) during emergency situations when there is a need to reverse Pradaxa’s blood-thinning effects.|
|Bristol-Myers Squibb||Empliciti (elotuzumab); BLA||In combination with two other therapies to treat people with multiple myeloma who have received one to three prior medications|
|Bristol-Myers Squibb||Daklinza (daclatasvir); NDA||For use with sofosbuvir to treat hepatitis C virus genotype 3 infections|
|Daiichi Sanyko||Savaysa (edoxaban); NDA||Reduce the risk of stroke and dangerous blood clots in patients with atrial fibrillation that is not caused by a heart valve problem.|
|Eisai||Lenvima (lenvatinib); NDA; orphan drug||Progressive, differentiated thyroid cancer whose disease progressed despite receiving radioactive iodine therap|
|Eli Lilly and Company||Portrazza (necitumumab); BLA||In combination with two forms of chemotherapy to treat patients with advanced (metastatic) squamous non-small cell lung cancer who have not previously received medication specifically for treating their advanced lung cancer|
|GlaxoSmithKline||Nucala (mepolizumab); BLA||With other asthma medicines for the maintenance treatment of asthma in patients age 12 years and older|
|Gilead Sciences||Genvoya (a fixed-dose combination of elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide); NDA||HIV-1 infection in adults and pediatric patients 12 years of age and older|
|Johnson & Johnson (Janssen Biotech)||Darzalex (daratumumab); BLA||To treat patients with multiple myeloma who have received at least three prior treatments|
|Johnson & Johnson (Janssen Products)||Yondelis (trabectedin); NDA||Specific soft tissue sarcomas, liposarcoma and leiomyosarcoma, that cannot be removed by surgery or is advanced|
|Merck & Co.||Bridion (sugammadex); NDA||To reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide|
|Novartis||Farydak (panobinostat); NDA; orphan drug||Multiple myeloma|
|Novartis||Cosentyx (secukinumab); BLA||Moderate-to-severe plaque psoriasis|
|Novartis||Odomzo (sonidegib); NDA||Locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or for patients who are not candidates for surgery or radiation therapy|
|Novartis||Entresto (sacubitril/valsartan); NDA||Chronic heart failure|
|Novo Nordisk||Tresiba (insulin degludec injection); NDA||To improve blood sugar (glucose) control in adults with diabetes mellitus.|
|NPS Pharmaceuticals/Shire||Natpara (parathyroid horomone); BLA||Control hypocalcemia (low blood calcium levels) in patients with hypoparathyroidism|
|Otsuka Pharmaceutical||Rexulti (brexpiprazole); NDA||Adults with schizophrenia and as an add-on treatment to an antidepressant medication to treat adults with major depressive disorder|
|Pfizer||Ibrance (palbociclib); NDA||Metastatic breast cancer|
|Relypsa||Veltassa (patiromer sorbitex calcium); NDA||Hyperkalemia (high potassium levels)|
|Roche/Genentech||Cotellic (cobimetinib); NDA||In combination with vemurafenib to treat advanced melanoma that has spread to other parts of the body or can’t be removed by surgery, and that has a certain type of abnormal gene (BRAF V600E or V600K mutation)|
|Roche/Genentech||Alecensa (alectinib); NDA||Advanced ALK-positive non-small cell lung cancer|
|Sanofi/Regeneron Pharmaceuticals||Praluent (alirocumab); BLA||For certain patients with high cholesterol|
|Sprout Pharmaceuticals||Addyi (flibanserin); NDA||Acquired, generalized hypoactive sexual desire disorder in premenopausal women|
|Taiho Oncology||Lonsurf (trifluridine and tipiracil) NDA||Advanced colorectal cancer|
|Takeda Pharmaceuticals||Ninlaro (ixazomib); NDA||In combination with two other therapies to treat people with multiple myeloma who have received at least one prior therapy.|
|Tesaro||Varubi (rolapitant); NDA||To prevent delayed phase chemotherapy-induced nausea and vomiting|
|The Medicines Company||Kengreal (cangrelor); NDA||Anticoagulant for adult patients undergoing percutaneous coronary intervention|
|United Therapeutics||Unituxin (dinutuximab); BLA;||First-line therapy for pediatric patients with high-risk neuroblastoma|
|Vertex Pharmaceuticals||Orkambi (lumacaftor and ivacaftor); NDA||Cystic fibrosis in patients who have two copies of a specific mutation|
|Wellstat Therapeutics||Xuriden (uridine triacetate); NDA||Hereditary orotic aciduria, a rare metabolic disorder|
Actavis changed its corporate name to Allergan in June 2015.
So how do the 45 NMEs approved in 2015 compare with previous years? The FDA’s CDER approved 41 NMEs in 2014, 30 NDAs (i.e., small molecules) and 11 BLAs (i.e., biologics), both recent highs in terms of overall NME approvals and the number of approvals of new biologics by CDER. In comparison, FDA’s CDER approved 27 NMEs in 2013 and 39 NMEs in 2012. From 2005 to 2013, CDER averaged 25 NME approvals per year, which was bolstered by approval levels in 2004 (36 NMEs approved), 2011 (30 NMEs approved), 2012 (39 NMEs approved), and 2013 (27 NMEs approved). The period of 2005 to 2010 was a slower period for NME approvals. In 2005, 20 NMEs were approved, 22 in 2006, 18 in 2007, 24 in 2008, 26 in 2009, and 21 in 2010. Of the 172 NMEs approved over the past five years (2010 to 2015 to June 30, 2015), 137 or 80% were small molecules, and 35 or 20% were biologics. Table II summarizes NME approvals for small molecules and biologics.over the past five years (2010 to 2015 to date).
|Table II: Small Molecule and Biologics New Molecular Entities Approved by the US Food and Drug Administration’s Center for Drug Evaluation and Research, 2010 to 2015.|
|Year||Number of New Molecular Entities (NMEs) Approved||Number of NME NDAs approved (small molecules) and NME BLAs approved (biologics)|
|2010||21 NMEs approved||15 NDAs (small molecules) and 6 BLAs (biologics)|
|2011||30 NMEs approved||24 NDAs (small molecules) and 6 BLAs (biologics)|
|2012||39 NMEs approved||33 NDAs (small molecules) and 6 BLAs (biologics)|
|2013||27 NMEs approved||24 NDAs (small molecules) and 3 BLAs (biologics)|
|2014||41 NMEs approved||30 NDAs (small molecules) and 11 BLAs (biologics)|
|2015||45 NMEs approved||33 NDAs (32 small molecules and one insulin analogue*), 12 BLAs (biologics)|
|Note: Novo Nordisk’s Tresiba (insulin degludec injection) is a long-acting basal human insulin analog produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification. It was approved as a new drug application not as a biologics license application.
Source: US Food and Drug Administration’s Center for Drug Evaluation and Research
Novartis and Allergan lead the pack
Among the large pharmaceutical companies, Novartis and Allergan were the leaders in terms of NME approvals in 2015. Novartis has had four NME approved: Cosentyx (secukinumab) for treating moderate-to-severe plaque psoriasis,;Farydak (panobinostat) for treating multiple myeloma; Odomzo (sonidegib) for treating locally advanced basal cell carcinoma (i.e., skin cancer); and Entresto (sacubitril/valsartan) for treating chronic heart failure;
Novartis points to high growth potential for Cosentyx (secukinumab), which was approved in the US and Europe in January 2015. Industry analysts are also bullish on Cosentyx as a potential blockbuster. A recent Thomson Reuters analysis estimates 2019 sales for Cosentyx at nearly $1.1 billion. Novartis is even more bullish, offering peak sales potential based on approval of additional indications in psoriasis and arthritis indications of $4 billion to $5 billion.
Secukinumab is an antibody that binds to a protein (interleukin (IL)-17A), which is involved in inflammation. By binding to IL-17A, secukinumab prevents it from binding to its receptor, and inhibits its ability to trigger the inflammatory response that plays a role in the development of plaque psoriasis. In addition to the US and EU, Cosentyx has been approved in Switzerland, Chile, Australia, Canada, and Singapore for the treatment of moderate-to-severe plaque psoriasis and in Japan for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis. Cosentyx is also in Phase III development for psoriatic arthritis and ankylosing spondylitis with regulatory applications made for the US and EU. Novartis said that is expects an opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use in the first half of 2016 and potential approval by the FDA in the second half of 2016 for these indications. Overall, Novartis said that Cosentyx is expected to be a blockbuster and that a scenario where it could reach peak sales of $4 billion to $5 billion in psoriasis and arthritis indications is possible.
Novartis’ Entresto (sacubitril and valsartan) for treating chronic heart failure is another potential blockbuster for Novartis, which received US approval in 2015 with regulatory review pending in the European Union. A recent Thomson Reuters analysis estimates 2019 sales for Entresto at $3.7 billion. Entresto is an ARNI (angiotensin receptor neprilysin inhibitor) and has a mode of action that is thought to reduce the strain on the failing heart. It harnesses the body’s natural defenses against heart failure, simultaneously acting to enhance the levels of natriuretic and other endogenous vasoactive peptides while also inhibiting the renin-angiotensin-aldosterone system (RAAS).
Novartis’ Farydak (panobinostat) for treating multiple myeloma and Odomzo (sonidegib) for treating locally advanced basal cell carcinoma are latest products in the company’s oncology portfolio, which Novartis recently bolstered with its acquisition of the oncology assets of GlaxoSmithKline (GSK). The acquisition of GSK’s oncology assets strengthened Novartis’ position in hematology, breast cancer, and renal cell carcinoma and provided Novartis with key assets in melanoma. Novartis acquired GSK’s oncology products, including two pipeline candidates, for an aggregate cash consideration of $16 billion. Up to $1.5 billion of this amount is contingent on certain development milestones. With the closing of the deal, Novartis’ oncology portfolio now includes 22 oncology and hematology medicines to treat more than 25 conditions. Some key products from GSK’s acquisition include: Tafinlar (dabrafenib), a BRAF inhibitor, and Mekinist (trametinib), a MEK inhibitor, both approved for the treatment of metastatic melanoma; Votrient, a VEGFR inhibitor for treating renal cell carcinoma; Promacta (eltrombopag) for treating thrombocytopenia; Tykerb (pazopanib) for treating HER2+ metastatic breast cancer; and Arzerra (ofatumumab) for treating chronic lymphocytic leukemia. Sales of the acquired GSK oncology products in 2014 were approximately $2.0 billion. In oncology, Novartis estimates that it is the number two player globally following the acquisition of the GSK oncology assets combined with the company’s existing portfolio and pipeline. Novartis’ oncology position is built around targeted therapies, immuno-oncology assets, and chimeric antigen receptors T cells (CART) as both monotherapies and combination therapies.
Allergan (formerly Actavis) matches Novartis’ NME strength with three NME approvals and another NME gained from its $2.1 billion acquisition of Kythera Biopharmaceuticals. Through Forest Laboratories, which Allergan acquired in 2014 for $28 billion, Allergan received FDA approval this year for Vraylar (cariprazine) for treating schizophrenia and bipolar disorder in adults. Allergan also gained two additional NME approvals in 2015: Viberzi (eluxadoline) for treating irritable bowel syndrome with diarrhea and Avycaz (ceftazidime-avibactam) for treating adults with complicated intra-abdominal infections, in combination with metronidazole, and complicated urinary tract infections, including kidney infections (pyelonephritis). Avycaz is a fixed-combination drug containing ceftazidime, a previously approved cehalosporin antibacterial drug, and avibactam, a new beta-lactamase inhibitor. Avycaz was the fifth approved antibacterial drug product designated as a Qualified Infectious Disease Product (QIDP). This designation is given to antibacterial products to treat serious or life-threatening infections under the Generating Antibiotic Incentives Now (GAIN) title of the FDA Safety and Innovation Act.
Allergan also picked up another NME in 2015 through its $2.1 billion acquisition of Kythera Biopharmaceuticals. Allergan gained Kythera’s 2015 NME, Kybella (deoxycholic acid), which is used to treat moderate-to-severe fat below the chin or commonly known as double chin.
More NMEs with blockbuster potential
Among the large pharmaceutical companies, Amgen and Sanofi both scored NME approvals by the FDA for a new class of anti-cholesterol drugs, human monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C), or “bad” cholesterol, from the blood. Amgen’s Repatha (evolocumab) and Sanofi’s/Regeneron’s Praluent (alirocumab) are pegged as potential blockbusters. Based on estimates for 2019 sales, a recent Thomson Reuters analysis puts potential revenues at Regeneron Pharmaceuticals and Sanofi’s Praluent (alirocumab) at $4.4 billion, and Amgen’s’ evolocumab at nearly $1.9 billion by 2019. In addition to receiving US approval, both drugs have been approved in the European Union.
Pfizer and Otsuka Pharmaceutical also received approval for drugs with blockbuster potential. Otsuka received FDA approval for Rexulti (brexpiprazole), an psychotropic compound discovered by Otsuka and co-developed with Lundbeck, for treating adults with schizophrenia and as an add-on treatment to an antidepressant medication to treat adults with major depressive disorder. The Thomson Reuters analysis estimates potential 2019 sales of $1.35 billion. Pfizer’s Ibrance (palbociclib), a drug to treat advanced (metastatic) breast cancer, is expected to be a strong performer for Pfizer, with the Thomson Reuters analysis offering 2019 sales estimates of $2.756 billion. Ibrance is a kinase inhibitor indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease.
Other NME approvals
In addition to its approval for Repatha, Amgen had one other NME approval in 2015: Corlanor (ivabradine), which is for reducing hospitalization from worsening heart failure. Corlanor is a hyperpolarization-activated cyclic nucleotide-gated channel blocker approved for use in certain people who have long-lasting (chronic) heart failure caused by the lower-left part of their heart not contracting well. The drug is indicated for patients who have symptoms of heart failure that are stable, a normal heartbeat with a resting heart rate of at least 70 beats per minute, and are also taking beta blockers at the highest dose they can tolerate. The European Medicines Agency approved the drug in 2005 to treat stable angina and then approved it in 2012 to treat chronic heart failure.
Bristol-Myers Squibb had two NME approvals: Empliciti (elotuzumab) for treating multiple myeloma and Daklinza (daclastasvir) for treating hepatatis C (genotype 3) infections as did Johnson & Johnson with approval of Darzalex (daratumumab) for treating multiple myeloma and Yondelis (trabectedin) for treating specific soft tissue sarcomas. GlaxoSmithKline, Eli Lilly, and Takeda each had one NME approval, respectively Nucala (mepolizumab) for treating asthma, Portrazza (necitumumab) for treating advanced squamous non-small lung cancer, and Ninlaro (ixazomib) for treating multiple myeloma.
AstraZeneca had two NME approvals in 2015: Zurampic (lesinurad) for treating high levels of uric acid in the blood (hyperuricemia) associated with gout and Tagrisso (osimertinib) for treating non-small-cell lung cancer. Roche/Genentech also had two NME approvals: Alecensa (alectinib) for treating advanced ALK-positive non-small cell lung cancer and Cotellic (cobimetinib) for treating advanced melanoma. Merck & Co. scored one NME approval: Bridion (sugammadex), a drug that reverses the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide.
Among the other large pharma companies, Shire (through its acquisition of NPS Pharmaceuticals), Astellas Pharbma, Daiichi Sanyko, and Eisai each have had one NME approved in 2015. Through its $5.2 billion acquisition of NPS in 2015, Shire gained the FDA-approved NME, Natpara (parathyroid hormone), for controlling hypocalcemia (low blood calcium levels) in patients with hypoparathyroidism, a rare endocrine disorder characterized by insufficient levels of the parathyroid hormone.
Astellas Pharma received FDA approval for Cresemba (isavuconazonium), a new antifungal drug product used to treat adults with invasive aspergillosis and invasive mucormycosis, rare but serious infections. Aspergillosis is a fungal infection caused by the Aspergillus species, and mucormycosis is caused by the Mucorales fungi. These infections occur most often in people with weakened immune systems. Cresemba belongs to a class of drugs called azole antifungal agents, which target the cell membrane of a fungus. Cresemba is the sixth approved antibacterial or antifungal drug product designated as a QIDP and the second in 2015 following the approval of Allergan’s Avycaz (ceftazidime-avibactam). As part of its QIDP designation, Cresemba was given priority review, which provides an expedited review of the drug’s application. The QIDP designation also qualifies Cresemba for an additional five years of marketing exclusivity to be added to certain exclusivity periods already provided by the Food, Drug, and Cosmetic Act. As these types of fungal infections are rare, the FDA also granted Cresemba orphan drug designations for invasive aspergillosis and invasive mucormycosis.
Eisai received FDA approval for Lenvima (lenvatinib) for treating progressive, differentiated thyroid cancer that has progressed despite receiving radioactive iodine therapy. Lenvima is a kinase inhibitor, which works by blocking certain proteins from helping cancer cells grow and divide. Daiichi Sankyo received approval for the anti-clotting drug, Savaysa (edoxaban tablets), to reduce the risk of stroke and dangerous blood clots (systemic embolism) in patients with atrial fibrillation that is not caused by a heart valve problem. Savaysa was also approved to treat deep vein thrombosis and pulmonary embolism in patients who have already been treated with an anti-clotting drug administered by injection or infusion (parenterally), for five to ten days.
Through its pending $1 billion acquisition of Sprout Pharmaceuticals, Valeant Pharmaceuticals International, Inc. will gain a NME, Addyi (flibanserin), to treat acquired, generalized hypoactive sexual desire disorder in premenopausal women. The deal was announced in August 2015. Under terms of the acquisition agreement, Valeant will pay approximately $500 million, subject to customary purchase price adjustments, upon the closing of the transaction and an additional payment in the amount of $500 million, payable in the first quarter of 2016, plus a share of future profits based upon the achievement of certain milestones.
In other drug approvals, The Medicines Company received approval for Kengreal (cangrelor), an intravenous antiplatelet drug that prevents formation of harmful blood clots in the coronary arteries, the blood vessels that supply blood to the heart. It is approved for adult patients undergoing percutaneous coronary intervention, a procedure used to open a blocked or narrowed coronary artery to improve blood flow to the heart muscle.
There were several NME approvals in 2015 for orphan or rare diseases, Asklepion Pharmaceuticals received approval for Cholbam (cholic acid) capsules for treating pediatric and adult patients with bile acid synthesis disorders due to single enzyme defects, and for patients with peroxisomal disorders (including Zellweger spectrum disorders). Patients with these rare, genetic, metabolic conditions exhibit manifestations of liver disease, steatorrhea (presence of fat in the stool), and complications from decreased fat-soluble vitamin absorption. Individuals with these rare disorders lack the enzymes needed to synthesize cholic acid, a primary bile acid normally produced in the liver from cholesterol.
With the FDA approval of Cholbam in March 2015, the biopharmaceutical company, Retrophin, exercised its right to purchase from Asklepion all worldwide rights, titles, and ownership of Cholbam and related assets. Retrophin paid Asklepion a one-time cash payment of $27 million, in addition to approximately 661,278 shares of Retrophin common stock (initially valued at $9 million at the time of the announced agreement in January 2015), which assumed Cholbam received an approval for a CTX indication. Asklepion will also be eligible to receive up to $37 million in cumulative sales milestones, as well as tiered royalties based on future net sales of Cholbam. With the approval of Choblam, the FDA also granted Asklepion a Rare Pediatric Disease Priority Review Voucher (Pediatric PRV), a provision that encourages development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. This voucher is designed to be transferable or sold and provides the bearer with an expedited FDA review for any new drug application. The Pediatric PRV was transferred to Retrophin under the original terms of the agreement with Asklepion. In May 2015, Retrophin agreed to sell the pediatric voucher to Sanofi for $245 million ($150 million upfront followed by two equal installments of $47.5 million in 2016 and 2017).
This was the second time that Sanofi has purchased a pediatric PRV. In 2014, Sanofi and Regeneron Pharmaceuticals purchased a pediatric PRV from BioMarin GALNS Ltd., a direct, wholly owned subsidiary of BioMarin Pharmaceutical, Inc., which had received it through the FDA’s Rare Pediatric Disease Priority Review Voucher Program and the 2014 approval of BioMarin’s Vimizim (elosulfase alfa) for treating Mucopolysaccharidosis Type IVA (Morquio A syndrome). Sanofi and Regeneron equally shared the purchase price of PRV $67.5 million. Sanofi and Regeneron had purchased it for their BLA submission for alirocumab, is an investigational monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9), which is being evaluated for its potential to lower low-density lipoprotein cholesterol (LDL-C) in patients who are not at their current LDL-C target with standard lipid-modifying therapies. The priority review voucher entitles the holder to designate a BLA for priority review, which provides for an expedited 6-month review from the filing date instead of the standard 10-month review.
Wellstate Therapeutics’ Xuriden (uridine triacetate) was approved for treating hereditary orotic aciduria, a rare metabolic disorder, which has been reported in approximately 20 patients worldwide. Xuriden was granted a rare pediatric disease priority review voucher. In September 2014, Wellstat entered into an agreement with AstraZeneca under which the Pediatric Priority Review Voucher would be transferred to AstraZeneca upon approval. Financial terms of the agreement were disclosed.