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Alnylam Pharmaceuticals and Taiba Group Partner to Commercialize RNAi Therapeutics in the Gulf States

Business Wire 08 luglio 202016:18

Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, and taiba Middle East, a leading rare disease company based in the United Arab Emirates and covering the Middle East region, announced today that they have formed a Distribution Agreement for both ONPATTRO^® and GIVLAARI^®, the first-ever commercialized RNAi therapeutics, as well as another late-stage therapy in development for Primary Hyperoxaluria Type 1.

“The cooperation with taiba allows us to address the unmet medical needs of patients with rare diseases, particularly where those diseases have a higher regional prevalence. That is why it is so important that patients in the Middle East are not disadvantaged when it comes to accessing effective treatments,” said Brendan Martin, Vice President and Acting Head of Europe, Middle East & Africa, and Canada, Alnylam Pharmaceuticals. “taiba has a regional presence with operations in multiple Gulf states, and a proven track record of marketing and distributing medicines for rare diseases. Our collaboration marks an important first step in bringing our current and future therapies to those patients with urgent medical needs.”

“We are proud to collaborate with Alnylam in the Gulf states,” said Saif Al Hasani CEO of the taiba Group. “Alnylam’s portfolio of ground-breaking medicines will enhance our rare disease portfolio and enable us to offer innovative treatments to patients. Those patients with hATTR amyloidosis and other rare diseases deserve to have the earliest possible access to novel new treatments. We look forward to making this a reality, beginning with ONPATTRO and GIVLAARI.”

The Agreement between Alnylam and taiba will initially cover the Gulf states, including the Kingdom of Saudi Arabia, Kuwait, Bahrain, Qatar, Oman and the United Arab Emirates. It includes ONPATTRO, approved in the European Union (EU) in August 2018 for the treatment of hATTR amyloidosis in adults with stage 1 or stage 2 polyneuropathy; GIVLAARI, approved in the EU in March 2020 for the treatment of acute hepatic porphyria (AHP); and lumasiran, a late-stage investigational RNAi therapeutic for the treatment of Primary Hyperoxaluria Type 1 (PH1).

About ONPATTRO® (patisiran)
ONPATTRO is an RNAi therapeutic that was approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made. ONPATTRO blocks the production of TTR in the liver, reducing its accumulation in the body’s tissues in order to halt or slow down the progression of the polyneuropathy associated with the disease.

Important Safety Information (ISI) for ONPATTRO^®

Infusion-Related Reactions
Infusion-related reactions (IRRs) have been observed in patients treated with patisiran. In a controlled clinical study, 19% of patisiran-treated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with patisiran were flushing, back pain, nausea, abdominal pain, dyspnoea, and headache. Hypotension may also occur and syncope has been reported in the post-marketing setting.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, paracetamol, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to patisiran infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation
Patisiran treatment leads to a decrease in serum vitamin A levels. Patients receiving patisiran should take oral supplementation of approximately 2500 IU vitamin A per day to reduce the potential risk of ocular toxicity due to vitamin A deficiency. Doses higher than 2500 IU vitamin A per day should not be given to try to achieve normal serum vitamin A levels during treatment with patisiran, as serum levels do not reflect the total vitamin A in the body. Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. including reduced night vision or night blindness, persistent dry eyes, eye inflammation, corneal inflammation or ulceration, corneal thickening or corneal perforation).

Adverse Reactions

The most common adverse reactions that occurred in patients treated with patisiran were peripheral oedema (30%) and infusion-related reactions (19%).

For additional information about ONPATTRO, please see the full Prescribing Information.

About GIVLAARI^® (givosiran)
GIVLAARI is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) approved for the treatment of adults with acute hepatic porphyria (AHP) in the U.S. and for the treatment of AHP in adults and adolescents aged 12 years and older in the EU. In the pivotal ENVISION Phase 3 study, givosiran was shown to significantly reduce the annualized rate of composite porphyria attacks that required hospitalization, urgent healthcare visit or intravenous hemin administration at home compared to placebo. GIVLAARI is Alnylam’s first commercially available therapeutic based on its Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology to increase potency and durability. GIVLAARI is administered via subcutaneous injection once monthly at a dose based on actual body weight and should be administered by a healthcare professional. GIVLAARI works by specifically reducing elevated levels of ALAS1 messenger RNA, leading to reduction of toxins associated with attacks and other disease manifestations of AHP.

Important Safety Information for GIVLAARI^®

Contraindications
Givosiran is contraindicated in patients with known severe hypersensitivity to givosiran. Reactions have included anaphylaxis.

Anaphylactic Reaction
Anaphylaxis has occurred with givosiran treatment (<1% of patients in clinical trials). Ensure that medical support is available to appropriately manage anaphylactic reactions when administering givosiran. Monitor for signs and symptoms of anaphylaxis. If anaphylaxis occurs, immediately discontinue administration of GIVOSIRAN and institute appropriate medical treatment.

Hepatic Toxicity
Transaminase elevations (ALT) of at least 3 times the upper limit of normal (ULN) were observed in 15% of patients receiving givosiran in the placebo-controlled trial. Transaminase elevations primarily occurred between 3 to 5 months following initiation of treatment.

Measure liver function tests prior to initiating treatment with givosiran, repeat every month during the first 6 months of treatment, and as clinically indicated thereafter. Interrupt or discontinue treatment with givosiran for severe or clinically significant transaminase elevations. In patients who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly. The dose may be increased to the recommended dose of 2.5 mg/kg once monthly if there is no recurrence of severe or clinically significant transaminase elevations at the 1.25 mg/kg dose.

Renal Toxicity
Increases in serum creatinine levels and decreases in estimated glomerular filtration rate (eGFR) have been reported during treatment with givosiran. In the placebo-controlled study, 15% of patients receiving givosiran experienced a renally-related adverse reaction. The median increase in creatinine at Month 3 was 0.07 mg/dL. Monitor renal function during treatment with givosiran as clinically indicated.

Injection Site Reactions
In placebo-controlled and open-label clinical studies, injection site reactions have been reported in 36 % of patients Symptoms included erythema, pain, pruritus, rash, discoloration, or swelling around the injection site. Three patients (2.7 %) experienced a single, transient, recall reaction of erythema at a prior injection site with a subsequent dose administration.

Drug Interactions
Caution is recommended during the use of medicinal products that are substrates of CYP1A2 or CYP2D6 while on treatment with Givosiran as this medicinal product may increase or prolong their therapeutic effect, or alter their adverse event profiles Consider decreasing the CYP1A2 or CYP2D6 substrate dosage in accordance with the approved product labelling.

Adverse Reactions
The most common adverse reactions that occurred in patients receiving givosiran were nausea (32%), injection site reactions (36 %) and fatigue (22.5 %). The adverse reactions resulting in discontinuation of treatment were elevated transaminases (0.9 %) and anaphylactic reaction (0.9 %).

For additional information about GIVLAARI, please see full Prescribing Information.

About RNAi
RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Pharmaceuticals
Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylam’s commercial RNAi therapeutic products are ONPATTRO^® (patisiran), approved in the U.S., EU, Canada, Japan, Brazil, and Switzerland, and GIVLAARI^® (givosiran), approved in the U.S and the EU. Alnylam has a deep pipeline of investigational medicines, including six product candidates that are in late-stage development. Alnylam is executing on its "Alnylam 2020" strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam is headquartered in Cambridge, MA.

About taiba
taiba is a leading specialty marketing, sales and distribution company in the MENA region, providing innovative treatments to patients suffering from orphan and rare diseases. taiba’s vision is to cover the unmet medical need in its region, providing high quality products and a high level of service to healthcare organizations and hospitals, with a commitment to patient treatment. taiba’s focus is addressing the needs of rare disease patients and providing them with access to innovative medicines, either through named patient sales or commercialization. Over the last ten years, taiba has earned a reputation as a leading regional company in its segment and currently represents leading multinational companies that are pioneers in their fields such as Alexion, Aegerion, Biomarin, Chiesi, Dyax, Genzyme, Lucane, Veloxis and Vertex.

Alnylam Forward Looking Statements
Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam’s expectations regarding its collaboration with taiba and the possibility to address the unmet medical needs of patients with rare diseases, particularly where those diseases have a higher regional prevalence, its views with respect to taiba’s track record of marketing and distributing medicines for rare diseases, and expectations regarding the continued execution on its “Alnylam 2020” guidance for the advancement and commercialization of RNAi therapeutics constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or a future pandemic, such as the scope and duration of the outbreak, government actions and restrictive measures implemented in response, material delays in diagnoses of rare diseases, initiation or continuation of treatment for diseases addressed by Alnylam products, or in patient enrollment in clinical trials, potential supply chain disruptions, and other potential impacts to Alnylam’s business, the effectiveness or timeliness of steps taken by Alnylam to mitigate the impact of the pandemic, and Alnylam’s ability to execute business continuity plans to address disruptions caused by the COVID-19 or a future pandemic; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all; actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing; delays, interruptions or failures in the manufacture and supply of its product candidates, including lumasiran, or its marketed products; obtaining, maintaining and protecting intellectual property; intellectual property matters including potential patent litigation relating to its platform, products or product candidates; obtaining regulatory approval for its product candidates, including lumasiran, and maintaining regulatory approval and obtaining pricing and reimbursement for its products, including ONPATTRO and GIVLAARI; progress in continuing to establish a commercial and ex-United States infrastructure; successfully launching, marketing and selling its approved products globally, including ONPATTRO and GIVLAARI, and achieving net product revenues for ONPATTRO within its revised expected range during 2020; Alnylam’s ability to successfully expand the indication for ONPATTRO in the future; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's ability to manage its growth and operating expenses within the ranges of guidance provided by Alnylam through the implementation of further discipline in operations to moderate spend and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam’s ability to establish and maintain strategic business alliances and new business initiatives, including completing an agreement for funding by Blackstone of certain R&D activities for vutrisiran and ALN-AGT; Alnylam's dependence on third parties, including Regeneron, for development, manufacture and distribution of certain products, including eye and CNS products, Ironwood, for assistance with the education about and promotion of GIVLAARI, and Vir for the development of ALN-COV and other potential RNAi therapeutics targeting SARS-CoV-2 and host factors for SARS-CoV-2; the outcome of litigation; the risk of government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.