Alnylam Pharmaceuticals, Inc.NASDAQ
More Data From Alnylam Pharmaceuticals, But Not Much More Clarity
Stephen Simpson, CFA • 12 Comments
Stephen Simpson, CFA • 12 Comments
After Multiple Updates, Alnylam Hasn't Cleared Up Much
Stephen Simpson, CFA
Stephen Simpson, CFA
Tue, Nov. 15, 1:08 PM
- Alnylam (ALNY -3.9%) and collaboration partner The Medicines Company (MDCO -6.1%) hit the skids after the release of 180-day follow-up data from the Phase 2 ORION-1 study assessing inclisiran for the treatment of high cholesterol. The results were presented at the American Heart Association Annual Meeting in New Orleans, LA.
- Investors are heading for the exits in apparent response to the safety data. On slide #8, 54% (n=198/370) of patients treated with inclisiran experienced a treatment-emergent adverse event (TEAE), including 9% (n=34/370) considered serious or severe. For comparison purposes, the TEAE rate for placebo was also 54% (n=69/127), including 8% (n=10/127) considered serious or severe.
- There was one death (n=1/65) in the 500 mg cohort, however.
- The numbers for liver and muscle TEAEs (slide #9) do not appear to be unreasonable. Myalgia (muscle pain) occurred in 5.7% (n=21/370) of the pooled group while liver enzyme elevations were observed in only 1.4% (n=5/370). The rates for the 300 mg cohort were 6.6% (n=8/122) and 3.3% (n=4/122), respectively.
- The Medicines Company plans to advance inclisiran to Phase 3 development at the 300 mg dose.
- Inclisiran (PCSK9si) is an investigational GalNAc-conjugated RNAi therapeutic targeting PCSK9, a protein regulator of LDL receptor metabolism. In contrast to PCSK9 inhibitors, PCSK9si works by turning off PCSK9 synthesis in the liver.
Mon, Nov. 14, 9:25 AM
- Alnylam Pharmaceuticals (NASDAQ:ALNY) announces that global alliance partner Sanofi Genzyme (NYSE:SNY) will opt-in to co-develop and co-commercialize RNAi therapeutic fitusiran for the treatment of hemophilia and rare bleeding disorders in the U.S., Canada and Western Europe. Sanofi Genzyme had previously elected to exclusively develop fitusiran in their rest-of-world territories. A Phase 3 study is on tap to commence in early 2017.
- Under the terms of the alliance, Alnylam will receive up to $75M in development and regulatory milestones, including $25M upon the initiation of the Phase 3 trial. It will also earn tiered royalties up to 20% on fitusiran sales in Sanofi Genzyme's exclusive territory. Profits will be shared equally in the co-commercialization territory.
- Sanofi Genzyme has elected to pass on ALN-AS1, an investigational RNAi therapeutic for acute hepatic porphyrias.
- The companies formed their alliance in January 2014 to accelerate and expand the development and commercialization of RNAi therapeutics worldwide.
Mon, Nov. 14, 8:47 AM
- Alnylam Pharmaceuticals (NASDAQ:ALNY) is up 2% premarket and collaboration partner The Medicines Company (NASDAQ:MDCO) is up 8%, both on light volume, in response to increasing optimism regarding cholesterol-lowering candidate inclisiran (PCSK9si), an investigational GalNAc-conjugated RNAi therapeutic targeting PCSK9, a protein regulator of LDL receptor metabolism. It lowers bad cholesterol (LDL-C) by turning off PCSK9 synthesis in the liver.
- Results from a Phase 1 study was just published in The New England Journal of Medicine. The data showed doses of at least 300 mg (single or multiple) significantly lowered PCSK9 and LDL cholesterol for at least six months and was generally well-tolerated.
- Specifically, single doses of inclisiran of at least 300 mg reduced PCSK9 74.5% at Day 84. Doses at least 100 mg reduced LDL-C 50.6% at Day 84. The reductions were maintained at Day 180 will minor variation at doses at least 300 mg. Multiple doses reduced PCSK9 and LDL-C 83.8% and 59.7%, respectively, at Day 84. Levels remained reduced in all cohorts at Day 196.
- No serious adverse events were observed following single and multiple subcutaneous injections. All observed adverse events were mild or moderate in severity.
- Inclisiran was initially developed by Alnylam. The Medicines Company assumed the role of lead developer in August 2015. 180-day follow-up data from the Phase 2 ORION-1 study will be presented tomorrow, November 15, at the American Heart Association Annual Meeting in New Orleans, LA. Management will host a conference call at 3:00 pm ET tomorrow to discuss the results.
Wed, Nov. 2, 4:12 PM
Wed, Nov. 2, 4:05 PM
Tue, Nov. 1, 5:35 PM
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Mon, Oct. 10, 8:09 AM
- Alnylam Pharmaceuticals (NASDAQ:ALNY) announces that the Data Monitoring Committee (DMC) for its Phase 3 APOLLO study of patisiran in patients with hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN) met on October 7 and recommended continuation of the trial without modification. The APOLLO DMC met at the request of the Company following the decision announced on October 5 to discontinue development of revusiran for the treatment of hereditary ATTR amyloidosis with cardiomyopathy (hATTR-CM). The DMC will continue to meet periodically per their remit to monitor the overall safety of patisiran in APOLLO through its completion. Top-line data are expected in mid-2017.
- ATTR amyloidosis is a progressively debilitating and often fatal disease caused by deposition of transthyretin (TTR) in peripheral tissues. TTR protein is produced primarily in the liver and is normally a carrier of vitamin A. In hereditary ATTR amyloidosis (hATTR), mutations in TTR cause abnormal amyloid proteins to accumulate and damage body organs and tissue, such as the peripheral nerves and heart, resulting in intractable peripheral sensory neuropathy, autonomic neuropathy, and/or cardiomyopathy.
- Shares are up 2% premarket, but only on turnover of 457.
Fri, Oct. 7, 11:57 AM
- Ionis Pharmaceuticals (NASDAQ:IONS) upgraded to Outperform from Market Perform by BMO Capital. Price target raised to $48 (42% upside) from $42.
- Catalyst Pharmaceuticals (NASDAQ:CPRX) upgraded to Overweight from Neutral by Piper Jaffray. Price target raised to $4 (199% upside) from $1.
- AmerisourceBergen (NYSE:ABC) upgraded to Market Outperform from Market Perform by Avondale Partners.
- Alnylam Pharmaceuticals (NASDAQ:ALNY) downgraded to Market Perform from Outperform by Leerink Swann. Price target lowered to $40 (14% upside) from $107. Downgraded to Equal Weight from Overweight by Barclays. Price target lowered to $50 (42% upside) from $85. Downgraded to Neutral from Overweight by JPMorgan. Downgraded to Equal Weight from Overweight by Morgan Stanley. Price target lowered to $36 (3% upside) from $38.
- Merrimack Pharmaceuticals (NASDAQ:MACK) downgraded to Neutral from Overweight with a $5.75 (2% upside) price target by JPMorgan.
- Iradimed (NASDAQ:IRMD) downgraded to Neutral from Buy by Roth Capital. Price target lowered to $11.50 (11% upside) from $28.
- Trinity Biotech (NASDAQ:TRIB) downgraded to Equal Weight from Overweight by Stephens & Co.
- Depomed (NASDAQ:DEPO) downgraded to Neutral from Buy by Mizuho Securities.
- Align Technology (NASDAQ:ALGN) downgraded to Neutral from Overweight with a $96 (8% upside) price target by Baird.
Thu, Oct. 6, 3:32 PM
- Biotech investors are sitting on the sell button today. The iShares Nasdaq Biotechnology ETF (IBB -2.4%) is down on increased volume. Shares have retraced over 5% since the recent close of 300 on September 22.
- Alnylam (ALNY -48%) is leading the rout after it announced that it was dropping development of RNAi candidate revusiran.
- Representative tickers: (AMGN -0.3%)(BIIB -1.3%)(GILD -1.9%)(CELG -1.4%)(BMY)(MRK -0.7%)(PFE -1.2%)(VRTX -3%)(ALXN -2.2%)
Thu, Oct. 6, 12:48 PM
Thu, Oct. 6, 11:00 AM
Thu, Oct. 6, 9:14 AM
Thu, Oct. 6, 6:46 AM
- BMO Capital upgrades Ionis Pharma (NASDAQ:IONS) to Outperform from Market Perform following yesterday's news that Alnylam (NASDAQ:ALNY) had discontinued its Revusiran program after observing an imbalance of deaths in treated patients.
- "We are increasing our TTR-Rx revenues in familial amyloidotic cardiomyopathy (FAC) and wild-type (wt) to reflect no competition, which is partly offset by a lower probability of success (45% from 50%), given similar drug mechanisms. Consequently, our price target increases to $48 from $42. We believe IONS shares could be pressured as investors perceive added risk to TTR-Rx. We recommend buying on weakness."
- In pre-market trading, IONS is -1% and ALNY is -43%.
Wed, Oct. 5, 6:39 PM
- Alnylam (NASDAQ:ALNY) craters 43% after hours on robust volume in response to its announcement that it has decided to terminate development of revusiran, an RNAi therapeutic for the potential treatment of hereditary ATTR amyloidosis (hATTR) with cardiomyopathy, an Orphan Drug designation. The company made its decision yesterday and communicated it to investigators, study sites and regulatory authorities.
- The problem appeared to be an unacceptable safety profile in the Phase 3 ENDEAVOR study following reports of new onset or worsening peripheral neuropathy (nerve damage) in revusiran-treated patients in the Phase 2 OLE trial. At the company's request, the Data Monitoring Committee met to review the reports and unblinded data from ENDEAVOR. Although, it did not find conclusive evidence of revusiran-related neuropathy it concluded that continued dosing was inappropriate due to an unfavorable benefit-risk profile, specifically an "imbalance" in mortality in the revusiran arm compared to placebo.
- The company says its decision does not affect Phase 3-stage patisiran, a candidate for the treatment of hATTR with polyneuropathy, or any other RNAi therapeutic program. It adds that an assessment of safety data across its other programs, including the ALN-PCSsc program with The Medicines Company (NASDAQ:MDCO), revealed no evidence of a drug-related neuropathy signal in over 800 patients with exposures up to 34 months. Investors appear unconvinced. MDCO is down 12% after hours on robust volume.
Wed, Oct. 5, 5:35 PM
Thu, Aug. 4, 4:02 PM