The Drugs To Watch: New Report Identifies 20 Of The Most Promising For 2014

By Peter Robins, Editorial & Content Manager for Life Sciences, Thomson Reuters

The end of 2013 saw numerous drugs change clinical phase or receive approval and launch, creating an exciting landscape for drugs to watch in 2014.  Whether it’s a new HIV drug gaining approval or the advancement of a rheumatoid arthritis therapy from phase II to phase III trials, The Ones to Watch, a quarterly report from Thomson Reuters, keeps a finger on the pulse of the most promising drugs by mining strategic data from Cortellis^TM Competitive Intelligence.

Using these insights, Thomson Reuters analysts found that orphan drugs feature prominently in the market, with the recent launch of two drugs for orphan cancer indications: Gazyva^TM and Valchlor^TM, and important phase transitions for several others. In the US there have been nearly 250 labeled indications relating to orphan drug designations approved since the enactment of the Orphan Drug Act in 1983. Cortellis Competitive Intelligence describes over 800 drugs that have received at least one orphan designation.

Other disease areas with promising drugs to watch include chronic lymphocytic leukemia, HIV, pulmonary arterial hypertension, and more.

Here are 20 drugs to watch for in 2014. Each has either launched or received approval or entered phase III, II, or I clinical trials during the final quarter of 2013.

LAUNCHED OR RECEIVING APPROVAL

1. Gazyva, created at Glycart Biotechnology, has been developed by Biogen Idec and Roche subsidiaries Genentech and Chugai. Gazyva causes cell death by binding to a similar target to Rituxan® and Bexxar®, and is approved for previously-untreated chronic lymphocytic leukemia (CLL), an indication for which Genentech has US orphan and breakthrough therapy designations.

2. With a cure for HIV infection still elusive, the disease is managed using drugs acting on different stages of the HIV lifecycle. Gilead Sciences’ oral HIV integrase inhibitor Vitekta has recently gained approval in the EU and Australia, and is only the second HIV integrase inhibitor to receive EU approval after Isentress.

3. Valchlor  is also new to the US market. Indicated for a rare form of non-Hodgkin’s lymphoma, Valchlor is a gel formulation of mechlorethamine developed by Actelion subsidiary Ceptaris. The drug has been used off-label in this way for some time, but the approval is based on orphan designation awarded to Ceptaris in Europe and the US.

4. Actelion also recently launched its oral ET-A and -B receptor antagonist, Opsumit (macitentan), for pulmonary arterial hypertension. Opsumit will compete with Actelion’s own Tracleer®, the current gold standard, but could still reach global sales of $1.1 billion a year by 2017, according to Cortellis Competitive Intelligence.

5. Novo Nordisk’s recombinant Factor VIII NovoEight® joins a crowded market that includes Novo Nordisk’s own N8-GP, following its recent approval in Europe and America to prevent bleeding in adult and child hemophiliacs. Despite potential market crowding, Cortellis Competitive Intelligence forecasts sales of over $100 million by 2017.

PHASE III TRIALS

6. Phase III trials recently began for Lu-AE58054, a novel 5-HT6 antagonist for Alzheimer’s disease (AD) from H Lundbeck and Otsuka. Lu-AE58054 already demonstrated significant improvement of cognitive function in an earlier phase II trial when administered with Aricept.

7. Alnylam’s phase III APOLLO study of patisiran, its lipid-encapsulated siRNA therapy for familial amyloid polyneuropathy (FAP) began late last year. Treatment options for FAP are limited to Vyndaqel® or liver transplantation, enabling patisiran to have received both fast track and orphan designations.

8. Duvelisib, an inhibitor of PI3K-delta and –gamma, originated at Takeda subsidiary Intellikine. It is now being developed by Infinity Pharmaceuticals, which began a phase III trial in November, following US and EU grant of orphan drug status for both CLL and small lymphocytic leukemia in April.

9. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer. In October, AstraZeneca began a phase III trial of selumetinib in patients with KRAS mutation-positive NSCLC. AstraZeneca has also partnered with Roche Molecular Systems to develop a device to detect these mutations.

10. Another drug to recently reach phase III is ertugliflozin for the treatment of type 2 diabetes (T2D). It was initially developed by Pfizer, but an agreement with Merck & Co covers ertugliflozin as well as fixed-dose combinations with Glucophage® or Januvia®.

PHASE II TRIALS

11. RXi Pharmaceuticals was founded by Craig Mello who, along with Andrew Fire, won the Nobel Prize in 2006 for work on RNAi. This quarter saw the company’s lead therapy, RXI-109, enter a phase II trial for the prevention of scar tissue formation.

12. Another drug recently advancing to phase II trials is GKT-137831, a NOX1 and NOX4 inhibitor from GenKyoTex being developed for diabetic nephropathy, the leading cause of chronic kidney disease in the US and Europe.

13. Cerecor is developing the selective NMDA receptor subunit 2B antagonist CERC-301 (MK-0657) for depression. A phase II trial began in November 2013 and later that month, the FDA granted fast track designation for major depressive disorder.

14. Twelve million Americans are prescribed opioids for chronic pain relief but over 90% experience diminished bowel frequency. Synergy Pharmaceuticals recently started a phase II trial of SP-333, a guanylate cyclase-C receptor agonist, for the treatment of opioid-induced constipation (OIC).

15. Santarus believes its SAN-300, a humanized monoclonal antibody to integrin alpha-1 beta-1 (VLA-1), represents a novel approach to rheumatoid arthritis and other diseases, and began a phase II trial for RA in December.

PHASE I TRIALS

16. Heptares Therapeutics was founded in 2007 to develop drugs against GPCRs. Its lead candidate, HTL-9936, is a selective muscarinic M1 agonist designed to improve cognitive function in patients with AD and other diseases, which recently entered the clinic for the first time.

17. Biodel has advanced BIOD-531, an ultra rapid-acting formulation of recombinant insulin, to phase I. It is intended as an alternative to Eli Lilly’s Humulin R for the increasing population of insulin-resistant type 2 diabetes patients and also by patients who use premixed insulins such as NovaLog or Humalog.

18. Seattle Genetics is developing SGN-LIV1A, a targeting antibody linked to the synthetic cytotoxic agent monomethyl auristatin E. The company initiated an American phase I trial in October to assess safety and activity in a sub-group of metastatic breast cancer patients.

19. In December, Xenetic Biosciences and Russian company Pharmasynthez initiated a phase I trial of their cystic fibrosis treatment, PulmoXen, comprising a polysialylated formulation of recombinant human DNase I to help reduce the viscosity of infected lung secretions.

20. Euroscreen’s NK3 antagonist, ESN-364 is the first NK3 antagonist optimized for use in women’s health. It is being developed for sex-hormone related disorders such as endometriosis, polycystic ovarian syndrome and uterine fibroids, and entered the clinic for the first time in late 2013.

The scene is set for 2014 to be an exciting year for these promising drugs. Keep your eyes on the latest advancements in clinical phases and approvals each quarter with The Ones to Watch report.